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  • Cell senescence and fibrotic lung diseases
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-17
    Rui-Ming Liu; Gang Liu

    Idiopathic pulmonary fibrosis (IPF) is a progressive fatal lung disorder with an unknown etiology and very limited therapeutic options. The incidence and severity of IPF increase with advanced age, suggesting that aging is a major risk factor for IPF. The mechanism underlying the aging-related susceptibility to IPF, however, remains unclear. Cellular senescence, a permanent arrest of cell growth, has been increasingly recognized as an important contributor to aging and aging-related diseases, including IPF. Senescent cells have been identified in IPF lungs and in experimental lung fibrosis models. Removal of senescent cells pharmacologically or genetically improves lung function and reverses pulmonary fibrosis induced by different stimuli in experimental fibrosis models. Treatment with senolytic drugs also improves clinical symptoms in IPF patients. These intriguing findings suggest that cellular senescence contributes importantly to the pathogenesis of fibrotic lung diseases and targeting senescent cells may represent a novel approach for the treatment of fibrotic lung disorders. In this mini review, we summarize the recent advance in the field regarding the role of cellular senescence in fibrotic lung diseases, with a focus on IPF.

  • Optimal lighting levels for stair safety: Influence of lightbulb type and brightness on confidence, dynamic balance and stepping characteristics
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-17
    Neil M. Thomas; Timmion Skervin; Richard J. Foster; Thomas D. O'Brien; Mark G. Carpenter; Constantinos N. Maganaris; Vasilious Baltzopoulos; Carolyn Lees; Mark A. Hollands

    Introduction Poor lighting has been associated with stair falls in young and older adults. However, current guidelines for illuminating stairs seem arbitrary, differ widely between sources, and are often difficult to interpret. Aims Here we examined the influence of real-world bulb illumination properties on stair descent safety in young and older adults, with a view to generating preliminary evidence for appropriate lightbulb use/stair illumination. Methods Stair tread illumination (lux) was measured in a standard UK home (2.23 m ceiling) from a low (50 W; 630 lm) and a high (103 W, 1450 lm) power compact fluorescent lamp (CFL) bulb from the time they were turned on until they reached full brightness. This enabled modelling of their illumination characteristics during warm up. Illumination was also measured from a low (40 W, 470 lm) and a high (100 W, 1521 lm) power LED bulb at first turn-on. Computer-controlled custom lighting then replicated these profiles, in addition to a Bright control (350 lx), on an instrumented staircase descended (3 × trials per light condition) by 12 young (25.3 ± 4.4 years; 5 males), 12 higher ability older (HAOA: 69.6 ± 4.7 years; 5 males) and 13 lower ability older (LAOA: 72.4 ± 4.2; 3 males) healthy adults. Older adults were allocated to ability groups based on physiological and cognitive function. Stair specific confidence was assessed prior to the first descent in each new lighting condition, and whole-body 3D kinematics (Vicon) quantified margins of stability and foot clearances with respect to the step edges. Mixed ANOVAs examined these measures for within-subject effects of lighting (×5), between-subject effects of age (×3) and interactions between lighting and age. Results Use of CFL bulbs led to lower self-reported confidence in older adults (20.37%, p = .01), and increased margins of stability (12.47%, p = .015) and foot clearances with respect to the step edges (10.36%, p = .003). Importantly, using CFL bulbs increased foot clearance variability with respect to the bottom step (32.74%, p = .046), which is where a high proportion of falls occur. Conclusion Stair tread illumination from CFL bulbs at first turn on leads to less safe stair negotiation. We suggest high powered LED bulbs may offer a safer alternative.

  • 更新日期:2020-01-16
  • Difference in sarcopenia prevalence and associated factors according to 2010 and 2018 European consensus (EWGSOP) in elderly patients with type 2 diabetes mellitus
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-15
    Mauren M. de Freitas; Vanessa L.P. de Oliveira; Thaiciane Grassi; Kamila Valduga; Maria Elisa P. Miller; Renata A. Schuchmann; Karen L.A. Souza; Mirela J. de Azevedo; Luciana V. Viana; Tatiana P. de Paula

    Objectives The aim of this study was to establish the prevalence of sarcopenia and associated factors in elderly patients with type 2 diabetes mellitus (DM) according to 2010 (EWGSOP1) and 2018 (EWGSOP2) European consensus. Design Cross-sectional study. Participants Elderly outpatients ≥60 years with type 2 DM and able to walk were recruited at the DM ambulatory care center of a public hospital in Porto Alegre from 2017 to 2018. Materials and methods The diagnosis of sarcopenia was performed according to EWGSOP1 and EWGSOP2. Muscle mass (MM) was assessed using bioelectrical impedance (BIA). Muscle strength (MS) was assessed using the handgrip strength (HS) test and physical performance (PP) by timed-up-and-go (TUG) test. Results We included 242 patients with 68.3 ± 5.6 years, 54% women, 78% white, DM duration 14(8–22) years, BMI 29.5 ± 4.5 kg/m2, and HbA1c 7.8 ± 1.5%. Overall prevalence of sarcopenia was 21%. In EWGSOP1 it was 16.9%. The GLM Poisson model was used to assess sarcopenia. Male sex increased the prevalence of sarcopenia by 33% (3.330 [1.747–6.350]; p < .001), and walking >5401 steps/day had a protective effect of 70% for the prevalence of sarcopenia (0.306 [0.127–0.739]; p = .029). Finally, age had an impact of 6% on prevalence of sarcopenia (1.06 [1.015–1.108]; p = .009) according to EWGSOP1. On the other hand, the prevalence was 7%, women had more sarcopenia (88%), and BMI was lower in the sarcopenic group when defined according to EWGSOP2. Conclusions The prevalence of sarcopenia was more than double when comparing EWGSOP1 (16.9%) and EWGSOP2 (7%). We believe that the difference in prevalence is due to modifications in MM and MS criteria. According to EWGSOP1, walking may have protective role in the prevalence of sarcopenia in elderly type 2 DM individuals.

  • Effects of aquatic exercise on insulin-like growth factor-1, brain-derived neurotrophic factor, vascular endothelial growth factor, and cognitive function in elderly women
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-15
    Doo-wang Kang; Eadric Bressel; Do-yeon Kim

    The purpose of this study was to investigate the effects of a 16-week aquatic exercise program on brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF) levels, as well as cognitive function in elderly women. The subjects were 20 elderly women aged 68–80 years, randomly divided into an aquatic exercise group (n = 10) and a control group (n = 10). The aquatic exercises were performed for 60 min, three times per week for 16 weeks, and the intensity was progressively increased every 4 weeks (40–50% of heart rate reserve (HRR) for weeks 1–4, 50–60% of HRR for weeks 5–8, 60–65% of HRR for weeks 9–12, and 65–70% of HRR for weeks 13–16). The data were analyzed using two-way repeated measures analysis of variance, paired t-test, and independent t-test with an alpha level to indicate significance set at.05 for all tests. After the 16-week aquatic exercise program, the BDNF and IGF-1 levels (p < .01, respectively), and cognitive function (p < .05) of the aquatic exercise group showed significant changes. BDNF, IGF-1, and cognitive function levels (p < .01, respectively) were significantly different between the aquatic exercise group and control group. The results of this study suggest that regular aquatic exercise in elderly women during the early stages of aging can increase the expression of BDNF and IGF-1, thus maintaining and improving cognitive function.

  • The effect of a mentally fatiguing task on postural balance control in young and older women
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-11
    Amanda J. Morris; Anita D. Christie

    The purpose of this study was to examine the effect of a mentally fatiguing task on postural responses to unexpected backward perturbations in sixteen young and sixteen older women. Postural responses were characterized by center of pressure (COP) displacement, corrective COP peak velocity, and electromyography (EMG) of the medial gastrocnemius. Older women had slower reaction time (p = .002), longer EMG onset times (p = .03), larger COP displacement (p = .001), and faster COP velocity (p = .02) than younger women overall. However, only young women experienced mental fatigue (slower reaction times; p = .001) and this was accompanied by significantly faster COP velocity during the mental fatigue condition (p = .02) than the control condition. Performance of mental fatigue task, not necessarily the development of mental fatigue, affects neuromuscular activation in young women only, but does not affect the magnitude of postural response to perturbation.

  • Inflammatory markers associated with fall recurrence and severity: The Bambuí Cohort Study of Aging
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-11
    Juleimar Soares Coelho de Amorim; Karen Cecília Lima Torres; Andréa Teixeira Carvalho; Olindo Assis Martins-Filho; Maria Fernanda Lima-Costa; Sérgio Viana Peixoto

    Background The aim of this study was to analyze the association between inflammatory markers and recurrent and severe falls in 1304 community-dwelling older adults from the Bambuí Cohort Study of Aging. Methods Information about falls in the previous 12 months was collected, and classified based on recurrence (two or more falls) and severity (requirement of medical attention). The screened biomarkers included interleukins (IL-1β, IL-6, IL-10, and IL-12, TNF), chemokines (CXCL8, CXCL9, CXCL10, CCL2, and CCL5), and high-sensitive C-reactive protein (hs-PCR). Potential confounders included sociodemographic, behavioral, and health indicators. Associations were evaluated through logistic regression, using odds ratios (OR) and 95% confidence intervals (95% CI), with Stata 13.1. Results The prevalence of recurrent and severe falls was 10.7% and 9.0%, respectively. After adjustments, elevated levels of IL-12 (OR: 1.92; 95% CI: 1.09–3.37) and CXCL9 (OR: 1.67; 95% CI: 1.05–2.66) were found to be associated with recurrent falls, while elevated levels of TNF (OR: 1.58; 95% CI: 1.01–2.50), IL-12 (OR: 2.04; 95% CI: 1.13–3.70), CXCL10 (OR: 1.75; 95% CI: 1.04–2.92), and CCL5 (OR: 1.90; 95% CI: 1.18–3.07) were associated with severe falls. Conclusions The results highlight a wide range of biomarkers not yet explored in the literature and suggest that inflammation may be an important component of recurrent and severe falls.

  • Age-related changes in muscle volume and intramuscular fat content in quadriceps femoris and hamstrings
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-09
    Maya Hioki; Nana Kanehira; Teruhiko Koike; Akira Saito; Kiyoshi Shimaoka; Hisataka Sakakibara; Yoshiharu Oshida; Hiroshi Akima

    Whether age-related changes in muscle components differ between the quadriceps femoris and hamstrings has remained unclear. This study aimed to compare the muscle volume and echo intensity-estimated intramuscular adipose tissue content of the vastus lateralis (VL) and long head of biceps femoris (BF) muscles between young and older adults. Thirty young adults (n = 15; mean age, 21 years) and older adults (n = 15; mean age, 71 years) participated in this study. Magnetic resonance imaging was performed to determine muscle volumes of the VL and BF, and muscle volume normalized to body weight (muscle volume/weight). Mean gray-scale echo intensity was calculated as the intramuscular adipose tissue index. Muscle volume/weight and echo intensity were normalized using Z-scores in young and older adults. Muscle volume/weight was lower in older adults than in young adults, and lower in overall women than in men for VL (both p ≤ 0.001) and BF (p ≤ 0.01 and p ≤ 0.05). Echo intensity was higher in older adults than in young adults for VL and BF (both p ≤ 0.001), but did not differ between men and women. Z-score of muscle volume/weight was lower in older adults than in young adults for VL (−2.41 ± 1.22; p < 0.05), and Z-score of echo intensity was higher in older adults than in young adults for BF (2.00 ± 0.68; p < 0.05). These results suggest that muscle volume of quadriceps femoris was lower in older adults than in young adults, whereas intramuscular adipose tissue content of hamstrings was greater in older adults than in young adults.

  • Foot web pentosidine does not covary strongly with age in four species of wild seabirds
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-08
    Angelika A. Aleksieva; Jason R. Treberg; Antony W. Diamond; Scott A. Hatch; Kyle H. Elliott

    Age is an important parameter for a variety of ecological applications, including population viability analyses, contaminants monitoring and targeting of individuals for conservation. While many organisms can be aged by annual rings, dentition and other techniques (i.e., fish otoliths, clam growth rings, mammal tooth wear), there are no minimally invasive biomarkers for accurately aging birds in the wild. For the past century, banding has been the only way to identify a bird of known age, which requires continuous effort on a large scale with possibly low return rates. Recent studies have identified pentosidine as a potential biomarker of chronological aging in several bird species. To test this idea in four species of long-lived seabirds, we collected skin biopsies from the foot webs of previously banded, known-age seabirds: black-legged kittiwakes (Rissa tridactyla; 0–19 y old), Atlantic puffins (Fratercula arctica; 5–26 y old), razorbills (Alca torda; 0–15 d old) and thick-billed murres (Uria lomvia; 0–35 y old). Foot web samples were specifically chosen because this was the least invasive site for substantial skin biopsy. Samples were analysed with high performance liquid chromatography to quantify pentosidine levels. Collagen levels were estimated through hydroxyproline assays to normalize pentosidine content across individuals. Kittiwakes displayed a weak correlation (r2 = 0.20) between age and pentosidine/collagen. Puffins (adults only, r2 = 0.02), razorbills (chicks only, r2 = 0.08), and murres (adults, r2 = 0.04) did not show any associations with age. We concluded that pentosidine content in the foot web does not appear to be a reliable method for aging seabirds in the wild. An absence of change in pentosidine in the foot web with age is further evidence that long-lived seabirds may maintain physiological performance into old age.

  • Sex-different associations between serum homocysteine, high-sensitivity C-reactive protein and sarcopenia: Results from I-Lan Longitudinal Aging Study
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-08
    Wei-Ju Lee; Li-Ning Peng; Ching-Hui Loh; Liang-Kung Chen

    Background Both serum homocysteine and high sensitivity C - reactive protein (hsCRP) are inflammatory markers related to vascular aging. Little was known about relationship between hsCRP and homocysteine and sarcopenia. The study aimed to explore the association between these two biomarkers and sarcopenia and its components. Methods Data of 1582 participants excerpted from first wave of I-Lan Longitudinal Aging Study. Sarcopenia was defined according to criteria of the Asian Working Group of Sarcopenia. Logistic regression was employed to examine the aforementioned associations. Results High levels of homocysteine (OR 1.9, 95% CI 1.0–3.6) and hsCRP (OR 3.9, 95% CI 2.2–6.9) were independently associated with sarcopenia. Both biomarkers were significantly associated with weakness (OR 2.9, 95%CI 2.1–4.0 for high level of homocysteine; OR 1.6, 95% CI 1.2–2.0 for high level of hsCRP) and slowness (OR 2.0, 95%CI 1.3–3.0 for high level of homocysteine; OR1.5, 95% CI1.1–2.2 for high level of hsCRP). Stronger associations between high levels of homocysteine and sarcopenia were noted in the women. Conclusion The study confirmed positive association between homocysteine, hsCRP and sarcopenia and further highlighted potential roles of both biomarkers in sarcopenia development. Intervention studies are needed to evaluate potential therapeutic benefits of lowering homocysteine and hsCRP in managing sarcopenia.

  • NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-07
    Nady Braidy; Yue Liu

    Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a multitude of biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signalling and immunoregulatory roles. The de novo synthesis of NAD+ is primarily dependent on the kynurenine pathway (KP), although NAD+ can also be recycled from nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NAD+ levels have been reported to decline during ageing and age-related diseases. Recent studies have shown that raising intracellular NAD+ levels represents a promising therapeutic strategy for age-associated degenerative diseases in general and to extend lifespan in small animal models. A systematic review of the literature available on Medline, Embase and Pubmed was undertaken to evaluate the potential health and/or longevity benefits due to increasing NAD+ levels. A total of 1545 articles were identified and 147 articles (113 preclinical and 34 clinical) met criteria for inclusion. Most studies indicated that the NAD+ precursors NAM, NR, nicotinamide mononucleotide (NMN), and to a lesser extent NAD+ and NADH had a favourable outcome on several age-related disorders associated with the accumulation of chronic oxidative stress, inflammation and impaired mitochondrial function. While these compounds presented with a limited acute toxicity profile, evidence is still quite limited and long-term human clinical trials are still nascent in the current literature. Potential risks in raising NAD+ levels in various clinical disorders using NAD+ precursors include the accumulation of putative toxic metabolites, tumorigenesis and promotion of cellular senescence. Therefore, NAD+ metabolism represents a promising target and further studies are needed to recapitulate the preclinical benefits in human clinical trials.

  • The intersection of exercise and aging on mitochondrial protein quality control
    Exp. Gerontol. (IF 3.080) Pub Date : 2020-01-03
    Yuan Zhang; Ashley Oliveira; David A. Hood

    Skeletal muscle quality and quantity are negatively impacted with age. Part of this decline in function can be attributed to alterations in mitochondrial turnover, and in the mechanisms that regulate mitochondrial homeostasis. Protein quality control within the mitochondria relies on a number of interconnected processes, namely the mitochondrial unfolded protein response (UPRmt), protein import and mitophagy. In particular, the post-transcriptional regulation of protein import into the organelle has generated considerable recent interest in view of its dynamic versatility. The capacity for import can be increased by chronic exercise, and diminished by muscle disuse, and defects in the import pathway can be rescued by exercise. Within mitochondria, the unfolded protein response (UPR) is activated if protein import is altered, or if protein misfolding takes place. This UPR generates retrograde signaling to the nucleus to activate compensatory gene expression and protein synthesis. Mitophagy is also elevated with age, contributing to the lower mitochondrial content in aging muscle. However, mitophagy is amenable to exercise adaptations, as it is activated with each exercise bout, presumably to mediate mitochondrial quality control. However, this response is attenuated in older subjects. Although not yet completely elucidated, numerous molecular processes involved in mitochondrial biogenesis and turnover are affected with age. The contrasting and often opposite consequences of exercise and age suggest that exercise can serve as non-pharmacological “mitochondrial medicine” for aging muscle to ameliorate mitochondrial content and function, via pathways that implicate organelle protein quality control mechanisms.

  • Cycle exercise improves vascular function and neuropathic symptoms in patients with type 2 diabetes and peripheral neuropathy: A randomized controlled trial
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-31
    Farhad Gholami; Hamieh Nazari; Milad Alimi

    Diabetic peripheral neuropathy (DPN) is associated with peripheral arterial disease and endothelial dysfunction. We investigated the effect of exercise training on the measures of superficial femoral artery (SFA) and neuropathic symptoms in patients with DPN. In a randomized-controlled trial, 31 volunteers with established DPN were randomly assigned to experimental or control groups. Experimental group performed exercise training (50%–70% of heart rate reserve, 30–45 min, 3 sessions/week) over 12 weeks. Before and 48 h after the experimental period a 5-min flow mediated dilation (FMD) response in SFA using Color Doppler Ultrasonography, fasting glucose level, HbA1c and neuropathic score were assessed. FMD% significantly increased in the experimental group (from 3.2 ± 1.1% to 5.7 ± 1.2%) compared to the control condition (P = 0.0001). However, no significant alteration occurred in resting baseline diameter and intima media thickness (P > 0.05). We also observed a significant improvement in fasting glucose, HbA1c and Michigan Diabetic Neuropathy Score (MDNS) following exercise intervention (all P < 0.05). Pearson's correlation coefficient indicated a significant correlation between the changes in MDNS and FMD (r = −0.6, P = 0.012) and also between MDNS and HbA1c (r = 0.57, P = 0.019). This finding may be clinically of considerable importance as metabolic and vascular factors have been indicated to be involved in the development of DPN.

  • l-Theanine attenuates liver aging by inhibiting advanced glycation end products in d-galactose-induced rats and reversing an imbalance of oxidative stress and inflammation
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-31
    Li Zeng; Ling Lin; Yingqi Peng; Dongyin Yuan; Sheng Zhang; Zhihua Gong; Wenjun Xiao

    Redox and inflammation imbalances are associated with increased levels of advanced glycation end products (AGEs), leading to the degeneration of body function. l-Theanine, derived from tea, reportedly inhibits AGE formation in vitro. We investigated the effects on AGE content, oxidative stress, and inflammatory factors in d-galactose-induced aging rats for prevention and treatment of age-related liver dysfunction. l-Theanine increased activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, thus enhancing total antioxidant capacity, and decreasing malondialdehyde and nitric oxide synthase levels in serum and liver. Levels of the pro-inflammatory factors, interleukin (IL)-1β, tumour necrosis factor-alpha, and IL-6 were decreased in serum and liver, whereas those of anti-inflammatory factors, IL-4 and IL-10, were increased in the serum. Further, l-theanine inhibited AGE production and decreased the levels of the liver function markers, alanine aminotransaminase and aspartate aminotransferase. It also significantly increased the mRNA expression levels of FoxO1 and downregulated NF-κB(p65) but suppressed the phosphorylation of both FOXO1 and NF-κB (p65). Moreover, l-theanine effectively attenuated d-galactose-induced oedema and vacuole formation, thus protecting the liver. Overall, l-theanine reversed the d-galactose-induced imbalance in oxidative stress and inflammatory responses, reduced AGEs content in aging rats, maintained homeostasis in the body, and ameliorated liver aging.

  • Aftereffects of prolonged Achilles tendon vibration on postural control are reduced in older adults
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-30
    Stéphane Baudry; Jacques Duchateau

    Aim To assess the change in the contribution of proprioceptive signal from leg muscles in postural control with ageing. Methods Fifteen young (~23 yr) and fifteen older adults (~68 yr) participated in Experiment 1, which consisted of recording the mean position of the centre of pressure (CoP), CoP path length, CoP velocity, and the amplitude of the Hoffmann (H) reflex and maximal M wave (MMAX) in the soleus muscle during upright standing, before and after 1 h of bilateral Achilles tendon vibration applied in seated posture. Eight young (~24 yr) and eight older adults (~67 yr) participated in Experiment 2 consisting of recording H-reflex and MMAX in seated posture before and after the 1-h vibration procedure used in Experiment 1. Results Immediately after the 1-h vibration, the mean CoP position shifted forward in both groups (p < 0.05), with a greater magnitude of change (% pre-vibration) in young [mean(SD); 74(41)%] than older adults [44(40)%; p < 0.05]. The CoP path length and velocity only increased in young adults after vibration (p < 0.05). The H-reflex amplitude decreased only in young adults after vibration [before: 35(12); after: 16(13)% Mmax, p < 0.05] during upright standing (Experiment 1), whereas it decreased similarly (p > 0.05) in young [before: 47(12)% Mmax; after: 28(17)% Mmax] and older adults [before: 34(13)% Mmax; after: 21(14)% Mmax] in seated posture (Experiment 2). Conclusion Prolonged Achilles tendon vibrations lead to lesser postural perturbation in older than in young adults, supporting the assumption of a decreased reliance on leg muscle proprioception in postural control with ageing.

  • Prevalence of sarcopenia as a comorbid disease: A systematic review and meta-analysis
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-28
    Jacob Pacifico; Milou A.J. Geerlings; Esmee M. Reijnierse; Christina Phassouliotis; Wen Kwang Lim; Andrea B. Maier

    Background Sarcopenia shares risk factors with various other age-related diseases. This meta-analysis aimed to determine the prevalence of sarcopenia as a comorbid disease. Methods Medline, EMBASE and Cochrane databases were searched for articles from inception to 8th June 2018, reporting the prevalence of sarcopenia in individuals with a diagnosis of cardiovascular disease (CVD), dementia, diabetes mellitus or respiratory disease and, if applicable their controls. No exclusion criteria were applied with regards to definition of sarcopenia, individuals' age, study design and setting. Meta-analyses were stratified by disease, definition of sarcopenia and continent. Results The 63 included articles described 17,206 diseased individuals (mean age: 65.3 ± 1.6 years, 49.9% females) and 22,375 non-diseased controls (mean age: 54.6 ± 16.2 years, 53.8% females). The prevalence of sarcopenia in individuals with CVD was 31.4% (95% CI: 22.4–42.1%), no controls were available. The prevalence of sarcopenia was 26.4% (95% CI: 13.6–44.8%) in individuals with dementia compared to 8.3% (95% CI: 2.8–21.9%) in their controls; 31.1% (95% CI: 19.8–45.2%) in individuals with diabetes mellitus compared to 16.2% (95% CI: 9.5–26.2%) in controls; and 26.8% (95% CI: 17.8–38.1%) in individuals with respiratory diseases compared to 13.3% (95% CI: 8.3–20.7%) in controls. Conclusions Sarcopenia is highly prevalent in individuals with CVD, dementia, diabetes mellitus and respiratory disease.

  • Higher dose of resveratrol elevated cardiovascular disease risk biomarker levels in overweight older adults – A pilot study
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-28
    R.T. Mankowski; L. You; T.W. Buford; C. Leeuwenburgh; T.M. Manini; S. Schneider; P. Qiu; S.D. Anton

    Older adults are at high risk of developing cardiovascular disease (CVD). Pre-clinical studies indicate that resveratrol (RSV), a polyphenol commonly found in grapes and red wine, may help prevent development of CVD. Based on our previous reports where the 300 mg and 1000 mg doses appeared safe and improved psychomotor function in a dose-dependent manner, our hypothesis was that RSV would reduce biomarkers of CVD risk in overweight, but otherwise healthy older adults and that 1000 mg would lower CVD biomarkers >300 mg. This analysis was performed on samples from older participants (65 years and older) who were randomized to a 90 day RSV treatment with 300 mg (n = 10), 1000 mg (n = 9) or placebo (n = 10). We measured levels of CVD risk biomarkers i.e. oxidized low-density lipoprotein (oxLDL), soluble E-selectin-1 (sE-selectin), soluble Intercellular Adhesion Molecule-1 (sICAM-1), Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), total plasminogen activator inhibitor (tPAI-1). Statistical significance was set at p < 0.05. Both sVCAM-1 and tPAI increased significantly more in the 1000 mg vs. 300 mg and placebo groups. Other biomarkers (300 mg vs. 1000 mg vs. placebo: oxLDL, sEselectin-1 and sICAM-1) followed the same trend toward higher levels in the 1000 mg group compared to the 300 mg and placebo groups, without reaching statistical significance. This pilot project suggests that a higher dose of RSV may increase the levels of CVD risk biomarkers in overweight older adults. Given no change in the CVD risk biomarkers in response to a lower dose, future studies should test the effects of different doses of RSV to evaluate potential detrimental effects of higher doses on CVD biomarkers and measures of cardiovascular function in older adults at risk for CVD.

  • IDO activation, inflammation and musculoskeletal disease
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-26
    Joy Ogbechi; Felix I. Clanchy; Yi-Shu Huang; Louise M. Topping; Trevor W. Stone; Richard O. Williams

    The IDO/kynurenine pathway is now established as a major regulator of immune system function. The initial enzyme, indoleamine 2,3-dioxygenase (IDO1) is induced by IFNγ, while tryptophan-2,3-dioxygenase (TDO) is induced by corticosteroids. The pathway is therefore positioned to mediate the effects of systemic inflammation or stress-induced steroids on tissue function and its expression increases with age. Disorders of the musculoskeletal system are a common feature of ageing and many of these conditions are characterized by an inflammatory state. In inflammatory arthritis and related disorders, kynurenine protects against the development of experimental arthritis, while inhibition or deletion of IDO1 increases its severity. The long-term regulation of autoimmune disorders may be influenced by the epigenetic modulation of kynurenine pathway genes, with recent data suggesting that methylation of IDO may be involved. Osteoporosis is also associated with abnormalities of the kynurenine pathway, reflected in an inversion of the ratio between blood levels of the metabolites anthranilic acid and 3-hydroxy-anthranilic acid. This review discusses evidence to date on the role of the IDO/kynurenine pathway and the highly prevalent age-related disorders of osteoporosis and rheumatoid arthritis and identifies key areas that require further research.

  • Haplotype analysis on association between variants of interleukin 6 (IL-6) and late-onset Alzheimer's disease in a Chinese Han population
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-23
    Jing Zhao; Ping Liu; Linlin Hua; Xiaopeng Yang; Zhilei Zeng; Xiaodong Li; Shanshan Wang; Yajun Liu; Yanqiu Liu; Yunliang Wang

    Objective The aim of this study was to evaluate the influence of single nucleotide polymorphisms (SNPs) in interleukin-6 (IL-6) gene and the haplotype on late-onset Alzheimer's disease (LOAD). Methods A total of 896 participants were enrolled, including 446 LOAD patients and 450 controls. Total genomic DNA was extracted from the blood of participants and genotyping was then performed. Hardy-Weinberg equilibrium test was conducted in controls. Multivariate analysis was performed to determine the association between 4 SNPs (rs1800796, rs7802308, rs1800795 and rs13447446) in IL-6 gene and LOAD. Pairwise LD analysis was employed to identify the association between haplotype and LOAD. Results Multivariate logistic analysis showed that T allele of rs7802308 and G allele of rs1800796 were correlated with decreased risk of LOAD, adjusted ORs were 0.68 (95% CI: 0.50–0.91) and 0.71 (95% CI: 0.51–0.92), respectively. However, rs1800795 and rs13447446 were not associated with LOAD. Pairwise LD analysis among the 4 SNPs showed that only rs1800796 and rs1800795 in IL-6 gene was in heavy LD, the D' value was >0.75 (0.825). In all samples, the haplotype C-G was observed most frequently in two groups, with 55.79% and 49.46% in the LOAD patients and controls, respectively. The results also indicated that haplotype G-C was significantly associated with decreased LOAG risk. Conclusions T allele of rs7802308 and G allele of rs1800796 were correlated with decreased risk of LOAD. The haplotype G-C were also correlated with decreased risk of LOAD.

  • Comparison of age-specific leg extensor muscle function torque-time and rapid velocity attributes across the adult lifespan: A relative deficiency investigation
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-20
    Brennan J. Thompson; Eric J. Sobolewski; Eric D. Ryan

    The purposes of this study were to examine the age-related differences in absolute and normalized torque-time parameters in five distinct groups across the adult life span, and the relationship between rapid strength and limb acceleration capacities across the lifespan. One-hundred and thirty-six healthy men were categorized as young athletes (n = 27; age = 20.7 yrs), young controls (n = 32; 21.9 yrs), middle young (n = 32; 49.8 yrs), middle old (n = 15; 58.9 yrs), and old (n = 30; 71.3 yrs) cohorts. Participants performed maximal voluntary contractions (MVCs) of the leg extensors under isometric and isokinetic (240 deg·s−1) conditions. Outcome measures included peak torque (PT), absolute and MVC normalized (norm) rate of torque development (RTD) at 50 and 200 ms, RTD50/PT ratio, and the rate of velocity development (RVD). The PT and absolute RTD at 200 ms declined from young to old age (P < .05). The middle age groups exhibited an overall preservation of early RTD, and a potential enhancement of early normalized RTD (P = .06 for middle young vs. controls, for RTDnorm50). The RTD50/PT ratio was higher in the middle young (P < .05) compared to both the young groups. Generally, the RVD declined more linearly and exhibited worse preservation at mid-life than the early absolute or normalized RTD variables. All absolute torque-time variables were correlated (r = 0.43–0.73, P < .001) to the RVD for all groups combined. These findings showed distinct age-related declines occurred for different muscle function parameters unique to specific stages of the lifespan. Normalized RTD variables may reveal plausible mechanisms of age-related neuromuscular changes and the RTD50/PT ratio may be a useful tool for determining relative deficiencies, such that mid-life adults (45–64 yrs) should address their relative limitation of PT by enhancing strength at mid-life, whereas older adults (65+ yrs) may need more emphasis on RTD improvements. In addition, both mid-life and older men should seek to improve rapid limb velocity capacities due to the susceptibility of RVD to decline more incrementally across the lifespan. Such information may help to improve anti-aging strategies by countering age-specific muscle function deficiencies and may improve mid-life adults' ability to transition better functionally into old age.

  • Kynurenine suppresses osteoblastic cell energetics in vitro and osteoblast numbers in vivo
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-17
    Jessica L. Pierce; Rachel L. Roberts; Kanglun Yu; Riley K. Kendall; Helen Kaiser; Colleen Davis; Maribeth H. Johnson; William D. Hill; Carlos M. Isales; Wendy B. Bollag; Mark W. Hamrick; Meghan E. McGee-Lawrence

    Aging is a progressive process associated with declining tissue function over time. Kynurenine, an oxidized metabolite of the essential amino acid tryptophan that increases in abundance with age, drives cellular processes of aging and dysfunction in many tissues, and recent work has focused on understanding the pathways involved in the harmful effects of kynurenine on bone. In this study, we sought to investigate the effects of controlled kynurenine administration on osteoblast bioenergetics, in vivo osteoblast abundance, and marrow fat accumulation. Additionally, as an extension of earlier studies with dietary administration of kynurenine, we investigated the effects of kynurenine on Hdac3 and NCoR1 expression and enzymatic deacetylase activity as potential mechanistic contributors to the effects of kynurenine on osteoblasts. Kynurenine administration suppressed cellular metabolism in osteoblasts at least in part through impaired mitochondrial respiration, and suppressed osteoblastic numbers in vivo with no concurrent effects on marrow adiposity. Deleterious effects of kynurenine treatment on osteoblasts were more pronounced in female models as compared to males. However, kynurenine treatment did not inhibit Hdac3's enzymatic deacetylase activity nor its repression of downstream glucocorticoid signaling. As such, future work will be necessary to determine the mechanisms by which increased kynurenine contributes to aging bone bioenergetics. The current study provides novel further support for the idea that kynurenine contributes to impaired osteoblastic function, and suggests that impaired matrix production by kynurenine-affected osteoblasts is attributed in part to impaired osteoblastic bioenergetics. As circulating kynurenine levels in increase with age, and human bone density inversely correlates with the serum kynurenine to tryptophan ratio, these mechanisms may have important relevance in the etiology and pathogenesis of osteoporosis in humans.

  • Gait analysis with videogrammetry can differentiate healthy elderly, mild cognitive impairment, and Alzheimer's disease: A cross-sectional study
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-17
    Felipe de Oliveira Silva; José Vinícius Ferreira; Jéssica Plácido; Daniel Chagas; Jomilto Praxedes; Carla Guimarães; Luiz Alberto Batista; Jerson Laks; Andrea Camaz Deslandes

    Gait parameters have been investigated as an additional tool for differential diagnosis in neurocognitive disorders. A videogrammetry system could be used to capture and analyze gait in older adults. Different motor conditions were used in three specific assessments: 10-m walk test (10mWT), timed up and go test (TUGT) and treadmill walk test (TWT). These tasks were compared among healthy elderly (HE = 17), mild cognitive impairment (MCI = 23) and Alzheimer's disease (AD = 23) patients. The aim was to select the better gait parameter to differentiate these groups among different motor tests conditions with videogrammetry analyses. One-way ANOVA, Kruskal-Wallis, and Bonferroni post-hoc test were used to compare variables among groups. Then, an effect size (ES) and a linear regression analysis were calculated. The gait parameters showed significant differences among groups in all tests conditions, but not in TWT. Gait velocity (controlled by confounding variables) in 10mWT and TUGT at usual speed and dual-task condition, predicts 39% and 53% of the difference among diagnoses, respectively. We concluded that a low-cost and practical video analysis could be able to differentiate HE, MCI, and AD in clinical assessments.

  • Aging membranes: Unexplored functions for lipids in the lifespan of the central nervous system
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-17
    Dorota Skowronska-Krawczyk; Itay Budin

    Lipids constitute a significant group of biological metabolites and the building blocks of all cell membranes. The abundance and stoichiometries of different lipid species are known to vary across the lifespan and metabolic state, yet the functional effects of these changes have been challenging to understand. Here we review the potentially powerful intersection of lipid metabolism, which determines membrane composition and aging. We first introduce several key lipid classes that are associated with aging and aging-related disease, where they are found in organisms, and how they act on membrane structure and function. Instead of neutral lipids, which have primary roles in energy storage and homeostasis, we review known functions for polar lipids that control the physicochemical properties of cell membranes. We then focus on aging processes in the central nervous system (CNS), which is enriched in lipids and is highly dependent on membrane structure for function. Recent studies show how lipids act not just as biomarkers of aging and associated changes in the CNS, but as direct mediators of these processes. As a model system, we explore how fatty acid composition in the retina impact aging and aging-related disease. We propose that the biophysical effects of membrane structure on fundamental eukaryotic processes - mitochondrial respiration and autophagy - provide avenues by which lipid dysregulation can accelerate aging processes. Finally, we lay out ways in which an increased understanding of lipid membrane biology can be applied to studies of aging and lifespan.

  • Association between advanced glycation end products, their soluble receptor, and mortality in the general population: Results from the CARLA study
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-16
    Helen Ebert; Maria Elena Lacruz; Alexander Kluttig; Andreas Simm; Karin Halina Greiser; Daniel Tiller; Nadja Kartschmit; Rafael Mikolajczyk

    Background Advanced glycation end products (AGEs) in the plasma are associated with a number of age-related diseases that possibly lead to reduced longevity. However, previous studies showed large inconsistencies in the association between AGEs or their soluble receptor (sRAGE) and mortality. We studied this association in a cohort study of general population and assessed the potential changes in this association over time. Methods We used data of 958 men and 802 women from the general population in Halle, Germany with a follow up of 12 years. The associations were assessed by means of Kaplan-Meyer survival curves and multivariable and time-varying Cox-regression. Results AGEs and sRAGE were either not or only weakly (and in the other direction than expected) associated with all-cause mortality after 12 years follow-up in men and women (AGEs: Hazard ratio (HR) = 0.93, 95% confidence interval (95%CI) = 0.83–1.05 for men; HR = 0.88, 95%CI = 0.74–1.05 for women; sRAGE: HR = 1.08, 95%CI = 0.95–1.23 for men; HR = 1.10, 95%CI = 0.92–1.30 for women). There was no change of the predictive values over the follow up time. Sub-analyses with participants with and without AGEs-related conditions (diabetes mellitus and decreased renal function), with age stratified groups (younger (<65 years) and older (≥65 years) participants), with cardiovascular disease mortality as the outcome and the AGE/sRAGE ratio as predictor provided similar results. Conclusions Our findings suggest a lack of the expected association with mortality and contribute to the inconsistent findings for plasma-measured AGEs, sRAGE, and AGE/sRAGE ratio.

  • Diagnostic value of miR-193a-3p in Alzheimer's disease and miR-193a-3p attenuates amyloid-β induced neurotoxicity by targeting PTEN
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-16
    Fengjun Cao; Zhongjie Liu; Guanjun Sun

    Objective Many microRNAs (miRNAs) have been reported to be aberrantly expressed in Alzheimer's disease (AD) patients. The present study aimed to explore the diagnostic value and neuroprotective role of miR-193a-3p in AD. Methods 108 sporadic AD patients and 93 healthy controls were included. An Aβ25–35 insult cellular AD model of PC12 and SH-SY5Y was established. The relative expression levels of miR-193a-3p were calculated using qRT-PCR. Receiver operating characteristic (ROC) curve was applied to evaluate the usefulness of miR-193a-3p for detecting AD. Cell viability and apoptotic rates were calculated. Luciferase reporter assay was performed to confirm the interaction between miR-193a-3p and PTEN. Results miR-193a-3p expression was downregulated in both AD patients and the cellular AD model (all P < 0.001). Remarkable positive association was detected between serum miR-193a-3p level and MMSE score in AD patients (r = 0.5889, P < 0.0001). The diagnostic sensitivity and specificity were 89.8% and 77.4%, respectively, and the area under the curve (AUC) was 0.914. Overexpression of miR-193a-3p weakened Aβ25–35 induced cell viability inhibition, and reduced Aβ25–35 induced cell apoptosis in PC12 cells (all P < 0.01). Downregulation of miR-193a-3p intensified the effect of Aβ25–35 PTEN was proved to be the target gene of miR-193a-3p. Conclusion MiR-193a-3p could be a novel biomarker for AD diagnosis, and may protect against neurotoxicity in AD by targeting PTEN.

  • Loss of NRF2 leads to impaired mitochondrial function, decreased synaptic density and exacerbated age-related cognitive deficits
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-13
    Jonathan A. Zweig; Maya Caruso; Mikah S. Brandes; Nora E. Gray

    Activation of the antioxidant regulatory transcription factor NRF2 (Nuclear factor erythroid-derived 2) regulates cellular bioenergetics and improves neuronal health in aging. Yet how NRF2 participates in maintaining synaptic, mitochondrial and cognitive function has not been fully elucidated. This study investigates how loss of NRF2 affects neuronal metabolism, synaptic density and cognitive performance in aged mice. Dendritic arborization as well as synaptic and mitochondrial gene expression was evaluated in hippocampal neurons isolated from mice lacking NRF2 (NRF2KO) and from wild-type (WT) C57BL6 mice. Mitochondrial function of these neurons was evaluated using the Seahorse XF platform. Additionally learning, memory and executive function were assessed in 20 month old NRF2KO and age-matched WT mice using conditioned fear response (CFR) and odor discrimination reversal learning (ODRL) tests. Hippocampal bioenergetics was profiled using mitochondria isolated from these animals and tissue was harvested for assessment of mitochondrial and synaptic genes. NRF2KO neurons had reduced dendritic complexity and diminished synaptic gene expression. This was accompanied by impaired mitochondrial function and decreased mitochondrial gene expression. Similar mitochondrial deficits were observed in the brains of aged NRF2KO mice. These animals also had significantly impaired cognitive performance and reduced synaptic gene expression as well. These data point to a role for NRF2 in maintaining mitochondrial and cognitive function during aging and suggest that the transcription factor may be a viable target for cognitive enhancing interventions. Because mitochondrial dysfunction and cognitive impairment also occur together in many neurodegenerative conditions there may be broad therapeutic potential of NRF2 activating agents.

  • Oxidative stress, inflammatory cytokines and body composition of master athletes: The interplay
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-09
    Samuel Silva Aguiar, Caio Victor Sousa, Lysleine Alves Deus, Thiago Santos Rosa, Marcelo Magalhães Sales, Rodrigo Vanerson Passos Neves, Lucas Pinheiro Barbosa, Patrick Anderson Santos, Carmen Silva Campbell, Herbert Gustavo Simões

    Unhealthy aging is associated with increased adiposity, inflammation and oxidative stress (OS), but the interactions between them have been poorly investigated in people growing old under vigorous lifelong exercise regimens. Therefore, we compared and analyzed the relationships between markers of inflammation, OS and adiposity in master athletes (MA), young (YC) and middle-aged controls (MC). Fifty-nine participants (MA, n = 30, 51.56 ± 8.61 yrs, minimum of 20 yrs of training; YC, n = 17, 22.70 ± 3.92 yrs; MC, n = 12, 45.54 ± 9.86 yrs) underwent body composition measurements, blood sampling for inflammation and OS measurements, and provided information regarding general health and training status. The MA and YC demonstrated higher catalase (CAT) and superoxide dismutase (SOD) activity, and higher CAT/TBARS (TBARS: thiobarbituric acid reactive substances) and SOD/TBARS ratios. The cytokines TNF-α and IL-6, and their soluble receptors sTNF-RI and sIL-6R were lower in YC compared to MC and MA (p < 0.05). Moreover, MA showed lower levels of sTNF-RI, IL-6 and sIL-6R and higher IL-10 and IL-10/IL-6 ratio compared to MC (p < 0.05). The body fat was negatively associated with antioxidant enzymes (CAT: r = −0.448 and SOD: r = −0.413) and IL-10 (r = −0.585) and positively correlated with pro-inflammatory cytokines (TNF-α: r = 0.278; sTNF-RI: r = 0.709; IL-6: r = 0.720: sIL-6R: r = 0.430) (p < 0.05). Further, CAT and SOD activities were inversely associated with inflammatory parameters (sTNF-RI, IL-6 and sIL-6R; p < 0.05). In conclusion, markers of OS and inflammation did not differ between MA and YC and were associated with adiposity. Moreover, MA were leaner than MC, similarly to YC. Thus, lifelong training clearly attenuates inflammation, OS, and adiposity, supporting an attenuated and healthy aging.

  • Chair-based exercise programs in institutionalized older women: Salivary steroid hormones, disabilities and frailty changes
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-06
    Guilherme Furtado, Humberto Moreira Carvalho, Marisa Loureiro, Miguel Patrício, Matheus Uba-Chupel, Juan C. Colado, Eef Hogervorst, José Pedro Ferreira, Ana Maria Teixeira

    Purpose Many people experience aging-related losses in different physical domains, which leads to a condition often called physical frailty (PF). The aim of this study was to analyse the effects of two different, 28-weeks, class chair-exercise protocols on salivary steroid hormones (SH), PF, and functional disabilities (FD) in frail older women. Methods A sample of older frail individuals (n = 60, 81 ± 7.84 years) participated in the study and were divided into three groups: chair elastic-band muscle strength exercises (CSE), n = 20), chair-multimodal exercise (CME, n = 21) and a control non-exercise group (CGne, n = 19). Both exercise programs consisted of 45 min of supervised chair-based exercise group classes, carried out 3 times/week. CME participants performed a progressive training using walking, mobility and body weight resistance exercises. The CSE participants exercised using an elastic-band system of progressive exercises. Both CSE and CME followed a circuit training protocol. The controls did not change their usual lifestyle. The indicators of PF, FD and SH concentrations were analyzed before and after the intervention. Results Both exercise programs diminished the PF status showing significant time and time versus treatment interactions (p < .01). An increase in the CME group, between baseline and 14-weeks, and in the CSE group, after 28 weeks, for Testosterone concentrations was observed (p < .01). Dehydroepiandrosterone (DHEA) increased after 28-weeks in the CME group and decreased in the CGne after the same period (p < .05). Both exercise programs decreased the negative scores of several FD domains, specially fear of falling that showed significant effects with time (p < .01), and time vs intervention (p < .05). Conclusion Both chair-exercise based programs were effective in stimulating positive changes in physical health and in steroid hormone responses, especially in DHEA. The control group did show a negative trend towards an increased PF status and decreased levels of SH. It is crucial for public health to identify the main factors associated with Functional Disability and Physical Frailty that underlie the development of new methods for complementary therapies, such as the use of low doses of hormonal supplementation combined with long-term exercise interventions.

  • Comparison of revised EWGSOP criteria and four other diagnostic criteria of sarcopenia in Chinese community-dwelling elderly residents
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-06
    Lei Yang, Xuemei Yao, Jing Shen, Gaofeng Sun, Qi Sun, Xiaoli Tian, Xiaoxia Li, Xue Li, Ledan Ye, Zhanlin Zhang, Jianghong Dai, Hui Xiao

    Objectives To compare the prevalence and associated factors of sarcopenia defined by the revised European Working Group on Sarcopenia in Older People (EWGSOP2) criteria with the initial European Working Group on Sarcopenia in Older People (EWGSOP1) criteria, the Asia Working Group for Sarcopenia (AWGS), the International Working Group on Sarcopenia (IWGS), and the National Institutes of Health (FNIH) Sarcopenia Project criteria among Chinese community-dwelling older adults. Design A cross-sectional study. Setting Two community health centers in Urumqi, China. Participants A total of 483 participants aged 60 years and older from the community. Measurement Anthropometry, skeletal muscle mass, handgrip strength, 4-m walking speed, and biochemical markers. Questionnaire collected information included demographics, lifestyle, and quality of life. Results The prevalence of EWGSOP2-defined sarcopenia (men: 6.5%; women: 3.3%) was lower than that defined by the EWGSOP1 (men: 22.3%; women 11.7%), AWGS (men: 10.9%; women: 8.0%), and IWGS (men: 24.5%; women: 11.0%) criteria, but higher than FNIH criteria (men: 6.0%; women: 1.7%). The positive percent agreement was lower (men: 15.6%–63.6%; women: 15.2%–40.0%), while negative percent agreement was higher (men: 96.4%–100.0%; women: 97.3%–99.6%). Sex (OR 0.31, 95% CI 0.12–0.81), education level (OR 0.49, 95% CI 0.29–0.83), and body mass index (BMI, OR 0.73, 95% CI 0.62–0.86) were associated with sarcopenia defined by the EWGSOP2 criteria. No consistent pattern of risk factors associated with sarcopenia in EWGSOP2 and four other diagnostic criteria was present. Conclusions and implications The EWGSOP2 criteria did not agree with the EWGSOP1, AWGS, IWGA, and FNIH criteria defining sarcopenia. Risk factors associated with the EWGSOP2-defined sarcopenia have no consistent patterns with the EWGSOP1, AWGS, IWGA, and FNIH criteria. Therefore, the validity of the EWGSOP2 consensus needs to be confirmed in further prospective studies.

  • Kynurenine inhibits autophagy and promotes senescence in aged bone marrow mesenchymal stem cells through the aryl hydrocarbon receptor pathway
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-05
    Dmitry Kondrikov, Ahmed Elmansi, Robert Tailor Bragg, Tanner Mobley, Thomas Barrett, Nada Eisa, Galina Kondrikova, Patricia Schoeinlein, Alexandra Aguilar-Perez, Xing-Ming Shi, Sadanand Fulzele, Meghan McGee Lawrence, Mark Hamrick, Carlos Isales, William Hill

    Osteoporosis is an age-related deterioration in bone health that is, at least in part, a stem cell disease. The different mechanisms and signaling pathways that change with age and contribute to the development of osteoporosis are being identified. One key upstream mechanism that appears to target a number of osteogenic pathways with age is kynurenine, a tryptophan metabolite and an endogenous Aryl hydrocarbon receptor (AhR) agonist. The AhR signaling pathway has been reported to promote aging phenotypes across species and in different tissues. We previously found that kynurenine accumulates with age in the plasma and various tissues including bone and induces bone loss and osteoporosis in mice. Bone marrow mesenchymal stem cells (BMSCs) are responsible for osteogenesis, adipogenesis, and overall bone regeneration. In the present study, we investigated the effect of kynurenine on BMSCs, with a focus on autophagy and senescence as two cellular processes that control BMSCs proliferation and differentiation capacity. We found that physiological levels of kynurenine (10 and 100 μM) disrupted autophagic flux as evidenced by the reduction of LC3B-II, and autophagolysosomal production, as well as a significant increase of p62 protein level. Additionally, kynurenine also induced a senescent phenotype in BMSCs as shown by the increased expression of several senescence markers including senescence associated β-galactosidase in BMSCs. Additionally, western blotting reveals that levels of p21, another marker of senescence, also increased in kynurenine-treated BMSCs, while senescent-associated aggregation of nuclear H3K9me3 also showed a significant increase in response to kynurenine treatment. To validate that these effects are in fact due to AhR signaling pathway, we utilized two known AhR antagonists: CH-223191, and 3′,4′-dimethoxyflavone to try to block AhR signaling and rescue kynurenine /AhR mediated effects. Indeed, AhR inhibition restored kynurenine-suppressed autophagy levels as shown by levels of LC3B-II, p62 and autophagolysosomal formation demonstrating a rescuing of autophagic flux. Furthermore, inhibition of AhR signaling prevented the kynurenine-induced increase in senescence associated β-galactosidase and p21 levels, as well as blocking aggregation of nuclear H3K9me3. Taken together, our results suggest that kynurenine inhibits autophagy and induces senescence in BMSCs via AhR signaling, and that this may be a novel target to prevent or reduce age-associated bone loss and osteoporosis.

  • Role of 7-chloro-4-(phenylselanyl) quinoline as an anti-aging drug fighting oxidative damage in different tissues of aged rats
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-04
    Cristiane Luchese, Anelise Barth, Gabriel Pereira da Costa, Diego Alves, Diogo La Rosa Novo, Márcia Foster Mesko, Ethel Antunes Wilhelm

    This study investigated whether subacute treatment with 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) presented antioxidant action in oxidative stress associated with aging in different rat tissues. We also investigated whether plasma selenium levels were altered by aging, as well as the contribution of 4-PSQ administration to these levels. Aged Wistar male rats (23 month old) were intragastrically treated with 4-PSQ (5 mg/kg) for seven days. On the 14th day of the experimental protocol, plasma was collected to determine selenium levels and biochemical markers of renal and hepatic damage. Furthermore, liver, kidney, spleen and cerebral cortex were removed to determine thiobarbituric acid reactive species (TBARS), non-protein thiols (NPSH), glutathione S-transferase (GST), catalase (CAT) and δ-aminolevulinate dehydratase (ALA-D). Our results showed that one or more parameters changed markedly in the liver, kidney, spleen and cerebral cortex of aged rats. Moreover, biochemical markers of renal and hepatic damage and selenium levels are changed in the plasma of aged rats. Treatment with 4-PSQ repaired redox homeostasis in tissues of aged rats, as well as plasma biochemical markers of renal and hepatic damage and selenium levels. In conclusion, 4-PSQ presented an antioxidant effect in tissues of aged rats, restoring selenium levels, and contributing to the restoration of the damage caused by aging. Thus, 4-PSQ could be a potential candidate for the management of age-related oxidative damage, acting as an anti-aging drug.

  • SOD1 deficiency alters gastrointestinal microbiota and metabolites in mice
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-12-02
    Haruka Sagi, Shuichi Shibuya, Tamotsu Kato, Yumiko Nakanishi, Arisa Tsuboi, Shigeharu Moriya, Hiroshi Ohno, Hirokuni Miyamoto, Hiroaki Kodama, Takahiko Shimizu

    Redox imbalance induces oxidative damage and causes age-related pathologies. Mice lacking the antioxidant enzyme SOD1 (Sod1−/−) exhibit various aging-like phenotypes throughout the body and are used as aging model mice. Recent reports suggested that age-related changes in the intestinal environment are involved in various diseases. We investigated cecal microbiota profiles and gastrointestinal metabolites in wild-type (Sod1+/+) and Sod1−/− mice. Firmicutes and Bacteroidetes were dominant in Sod1+/+ mice, and most of the detected bacterial species belong to these two phyla. Meanwhile, the Sod1−/− mice had an altered Firmicutes and Bacteroidetes ratio compared to Sod1+/+ mice. Among the identified genera, Paraprevotella, Prevotella, Ruminococcus, and Bacteroides were significantly increased, but Lactobacillus was significantly decreased in Sod1−/− mice compared to Sod1+/+ mice. The correlation analyses between cecal microbiota and liver metabolites showed that Bacteroides and Prevotella spp. were grouped into the same cluster, and Paraprevotella and Ruminococcus spp. were also grouped as another cluster. These four genera showed a positive and a negative correlation with increased and decreased liver metabolites in Sod1−/− mice, respectively. In contrast, Lactobacillus spp. showed a negative correlation with increased liver metabolites and a positive correlation with decreased liver metabolites in Sod1−/− mice. These results suggest that the redox imbalance induced by Sod1 loss alters gastrointestinal microflora and metabolites.

  • Cell aging and cellular senescence in skin aging — Recent advances in fibroblast and keratinocyte biology
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-30
    Florian Gruber, Christopher Kremslehner, Leopold Eckhart, Erwin Tschachler

    The aging of the skin is the most visible and obvious manifestation of organismal aging and may serve as a predictor of life expectancy and health. It is, however, also the human desire for long-lasting beauty that further raises interests in the topic, and thus considerable means and efforts are put into studying the mechanisms of skin aging in basic and applied research. Both medical und non-medical interests are of benefit for skin research in general because the results from these studies help to deepen our understanding of the complex molecular, biological, cell signaling, developmental and immunological processes in this organ. In fact, the skin is an ideal organ to observe and analyze the impact of extrinsic and intrinsic drivers of aging. Within the past five years technological advances like lineage tracing of cells in model organisms, intra-vital microscopy, nucleic acid sequencing at the single cell level, and high resolution mass spectrometry have allowed to study aging and senescence of individual skin cells within the tissue context, their signaling and communication, and to derive new hypotheses for experimental studies in vitro. In this short review we will discuss very recent developments that promise to extend the existing knowledge on cell aging and senescence of dermal fibroblasts and epidermal keratinocytes in skin aging.

  • Are depression and anxiety disorders associated with adductor pollicis muscle thickness, sleep duration, and protein intake in cancer patients?
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-30
    Débora E. de Sousa, Millena N. de Carli, Renata C. Fernandes, Daniella B. Trindade, Alessandro Laviano, Claude Pichard, Gustavo D. Pimentel

    Introduction Psychological disturbances may be associated with compromised body composition and food intake. However, this has not been elucidated totally. Thus, this study aimed to evaluate the prevalence of anxiety and depression, and whether there is an association between these disorders and adductor pollicis muscle thickness (APMT), protein intake and sleep duration, in gastrointestinal cancer patients. Methods A cross-sectional study evaluated 117 patients of both genders diagnosed with gastrointestinal cancer. Protein intake was assessed by the USDA food database; sleep duration by self-administered questionnaire; and APMT using the skinfold. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety (HADS-A) and depression (HADS-D). Results A total of 117 (65% male) patients were assessed, of which 40 (34%) had anxiety and 39 (33%) depression. There was a negative correlation between APMT and anxiety (r = −0.20, p = .020) and depression (r = −0.19, p = .03), and between anxiety and sleep duration (r = −0.30, p = .001). Although there was an inverse association between anxiety and APMT (OR: 0.88, 95%CI: 0.79–0.99, p = .032) and sleep duration (OR: 0.71, 95%CI: 0.58–0.87, p = .001), when adjusted for gender and age, the association remained only between anxiety and sleep duration (OR: 0.71, 95%CI: 0.58–0.87, p = .001). Conclusion One-third of gastrointestinal cancer patients were classified as expressing anxiety and depression. Additionally, only sleep duration is associated with anxiety.

  • Balance and motor functioning in subjects with different stages of cognitive disorders
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-30
    Mine Baydan, Hatice Caliskan, Burcu Balam-Yavuz, Songul Aksoy, Bilgehan Böke

    Background Approximately 30% of the elderly population is falling each year, resulting in a major health problem. Cognitive decline is an independent risk factor for fall. Mild cognitive impairment (MCI) is a cognitive decline that is higher than expected in the subjects' age but does not affect the activities of daily living Objective In the study, vestibulo-ocular reflexes, dynamic visual acuities and postural balances of subjects with mild cognitive impairment were evaluated and compared with the healthy control group. Methods For this purpose, 10 subjects with mild cognitive impairment and 10 healthy subjects from the same age group were included in the study. After the hearing test was applied to the subjects, videonistagmography, dynamic visual acuity and computerized dynamic posturography measurements were performed. Results Computerized Dynamic Posturography VEST parameter, SOT (Sensory Organization Test) 2, SOT 3, SOT 6 and Composite Balance Scores were significantly lower in the MCI group. There was no significant difference between the two groups in terms of videonistagmographic measurements. Dynamic Visual Acuity Perception Time Test scores of the subjects with mild cognitive impairment were significantly longer compared to the control group (p < 0.05). Conclusion As a result of the study, it was concluded that subjects with mild cognitive impairment were more prone to fall compared to control group and that these subjects should be included in fall prevention rehabilitation programs.

  • Okra polysaccharides can reverse the metabolic disorder induced by high-fat diet and cognitive function injury in Aβ1–42 mice
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-30
    Tingxu Yan, Tingting Nian, Bo Wu, Feng Xiao, Bosai He, Kaishun Bi, Ying Jia

    Epidemiological studies showed that a high-fat diet threatened human health seriously. It can induce various diseases, such as obesity, metabolic disturbance and cognitive dysfunction which also related to insulin signaling. In the present study, Aβ1–42 induced AD model mice and normal mice were given a standard diet and high-fat diet, respectively. Meanwhile, Okra polysaccharides were used to treat AD mice to explore the possible mechanism between Alzheimer's disease and insulin signals. Weight and blood glucose of mice were measured weekly. Through the Morris water maze and the novel object recognition test, the Okra polysaccharides could improve the cognitive impairment of the AD mice. In addition, we also performed the serum chemistry analysis of mice, studied the histopathological changes in the hippocampal CA1 region by HE staining and detected the expressions of AKT, PI3K, ERK1/2, and GSK3β in the hippocampus by western blot. These results suggested that a high-fat diet can aggravate the metabolic disorder in AD mice and Okra polysaccharides can significantly reverse the metabolic disorder induced by high-fat diet and cognitive function injury in AD mice.

  • Altered verbal fluency processes in older adults with age-related hearing loss
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-30
    David G. Loughrey, Serguei V.S. Pakhomov, Brian A. Lawlor

    Epidemiological studies have linked age-related hearing loss (ARHL) with an increased risk of neurocognitive decline. Difficulties in speech perception with subsequent changes in brain morphometry, including regions important for lexical-semantic memory, are thought to be a possible mechanism for this relationship. This study investigated differences in automatic and executive lexical-semantic processes on verbal fluency tasks in individuals with acquired hearing loss. The primary outcomes were indices of automatic (clustering/word retrieval at start of task) and executive (switching/word retrieval after start of the task) processes from semantic and phonemic fluency tasks. To extract indices of clustering and switching, we used both manual and computerised methods. There were no differences between groups on indices of executive fluency processes or on any indices from the semantic fluency task. The hearing loss group demonstrated weaker automatic processes on the phonemic fluency task. Further research into differences in lexical-semantic processes with ARHL is warranted.

  • Analysis of inflammatory markers and hormones in old cancer patients: A descriptive study
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-30
    Sandra De Breucker, Sylvie Luce, Rose Njemini, Ivan Bautmans, Lore Decoster, Tony Mets, Thierry Pepersack

    Advanced cancers are associated with a chronic inflammation, especially high interleukin-6 (IL-6) and with various levels of adipokines (leptin and adiponectin), while ghrelin counteracts the anorexigenic effect of leptin in cancer-induced anorexia-cachexia syndrome. We aimed to understand how IL-6, adipokines and ghrelin plasma levels could be influenced by cancer on the one hand, and by age, frailty, and nutritional status in old cancer patients on the other hand. Ninety-nine patients aged 79[76–83] years old were included. Sixty-six percent had advanced stages of cancer, and 34% had cachexia. Fifty percent were at risk of malnutrition, and 10% had overt malnutrition. None of the variables studied was significantly correlated with the advanced stage, or cachexia. In multiple regression, the only parameter significantly and positively associated with age was adiponectin (p = 0.008). Despite a high prevalence of frailty in our study, we did not find any independent association of frailty (assessed by G8) with IL-6, leptin, adiponectin, or ghrelin in multivariate analysis. We observed that a low albumin level was independently associated with a higher level of IL-6 (p < 0.0001), but not with the MNA score. However, leptin showed a positive correlation with BMI (p < 0.0001), confirming the persistence of a relationship between leptin and adiposity, even in older cancer patients. Finally, high IL-6 level was associated with a higher mortality rate (p = 0.027). In conclusion, IL-6, leptin, adiponectin, and ghrelin are not associated with advanced stages of cancer or cancer-induced cachexia in older subjects with cancer, but they are significantly correlated with anthropometric factors and body composition.

  • Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-30
    Sherwood Dalton, Kathryn Smith, Kanwar Singh, Helen Kaiser, Ravindra Kolhe, Ashis K. Mondal, Andrew Khayrullin, Carlos M. Isales, Mark W. Hamrick, William D. Hill, Sadanand Fulzele

    Kynurenine, a metabolite of tryptophan breakdown, has been shown to increase with age, and plays a vital role in a number of age-related pathophysiological changes, including bone loss. Accumulation of kynurenine in bone marrow stromal cells (BMSCs) has been associated with a decrease in cell proliferation and differentiation, though the exact mechanism by which kynurenine mediates these changes is poorly understood. MiRNAs have been shown to regulate BMSC function, and accumulation of kynurenine may alter the miRNA expression profile of BMSCs. The aim of this study was to identify differentially expressed miRNAs in human BMSCs in response to treatment with kynurenine, and correlate miRNAs function in BMSCs biology through bioinformatics analysis. Human BMSCs were cultured and treated with and without kynurenine, and subsequent miRNA isolation was performed. MiRNA array was performed to identify differentially expressed miRNA. Microarray analysis identified 50 up-regulated, and 36 down-regulated miRNAs in kynurenine-treated BMSC cultures. Differentially expressed miRNA included miR-1281, miR-330-3p, let-7f-5p, and miR-493-5p, which are important for BMSC proliferation and differentiation. KEGG analysis found up-regulated miRNA targeting glutathione metabolism, a pathway critical for removing oxidative species. Our data support that the kynurenine dependent degenerative effect is partially due to changes in the miRNA profile of BMSCs.

  • Long term breeding of the Lmna G609G progeric mouse: Characterization of homozygous and heterozygous models
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-30
    Anna Zaghini, Giuseppe Sarli, Catia Barboni, Mara Sanapo, Valeria Pellegrino, Alessia Diana, Nikolina Linta, Julie Rambaldi, Maria Rosaria D'Apice, Michela Murdocca, Massimiliano Baleani, Fabio Baruffaldi, Roberta Fognani, Rosaria Mecca, Anna Festa, Serenella Papparella, Orlando Paciello, Francesco Prisco, Stefano Squarzoni

    The transgenic LmnaG609G progeric mouse represents an outstanding animal model for studying the human Hutchinson-Gilford Progeria Syndrome (HGPS) caused by a mutation in the LMNA gene, coding for the nuclear envelope protein Lamin A/C, and, as an important, more general scope, for studying the complex process governing physiological aging in humans. Here we give a comprehensive description of the peculiarities related to the breeding of LmnaG609G mice over a prolonged period of time, and of many features observed in a large colony for a 2-years period. We describe the breeding and housing conditions underlining the possible interference of the genetic background on the phenotype expression. This information represents a useful tool when planning and interpreting studies on the LmnaG609G mouse model, complementing any specific data already reported in the literature about this model since its production. It is also particularly relevant for the heterozygous mouse, which mirrors the genotype of the human pathology however requires an extended time to manifest symptoms and to be carefully studied.

  • Sex specific effects of capsaicin on longevity regulation
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-29
    Jie Shen, Jianying Shan, Xiang Zhu, Peijing Yang, Dake Zhang, Boying Liang, Motao Li, Xiaohui Zang, Zhuoping Dai

    The consumption of spicy food in daily diets have been found to be inversely associated with human mortality. However, whether intake of spices is the reason for reduced mortality, and whether capsaicin, the main bioactive component of spices, plays a major role, remain elusive. Here, we report that low concentration of capsaicin can indeed extend life span. Capsaicin had no effect on food consumption, reproductive fitness, or stress tolerance. However, it did appear to decrease the daytime activity of females. We hypothesize that this decrease in activity may be a contributing factor in the life span extending property of capsaicin.

  • Mitochondrial uncoupling and longevity – A role for mitokines?
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-28
    Susanne Klaus, Mario Ost

    Aging has been viewed both as a random process due to accumulation of molecular and cellular damage over time and as a programmed process linked to cellular pathway important for growth and maturation. These views converge on mitochondria as both the major producer of damaging reactive oxidant species (ROS) and as signaling organelles. A finite proton leak across the inner mitochondrial membrane leading to a slight uncoupling of oxidative phosphorylation and respiration is an intrinsic property of all mitochondria and according to the “uncoupling to survive” hypothesis it has evolved to protect against ROS production to minimize oxidative damage. This hypothesis is supported by evidence linking an increased endogenous, uncoupling protein (UCP1) mediated, as well as experimentally induced mitochondrial uncoupling to an increased lifespan in rodents. This is possibly due to the synergistic activation of molecular pathways linked to life extending effects of caloric restriction as well as a mitohormetic response. Mitohormesis is an adaptive stress response through mitonuclear signaling which increases stress resistance resulting in health promoting effects. Part of this response is the induction of fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), two stress-induced mitokines which elicit beneficial systemic metabolic effects via endocrine action.

  • Kynurenine signaling through the aryl hydrocarbon receptor: Implications for aging and healthspan
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-28
    Helen Kaiser, Emily Parker, Mark W. Hamrick

    The tryptophan metabolite kynurenine increases with aging and inflammation, and appears to contribute directly to the development and progression of several age-related conditions. Kynurenine is now known to signal through the aryl hydrocarbon receptor (Ahr) to modulate levels of reactive oxygen species (ROS). The Ahr promoter region contains several sites for NF-kB binding, indicating that inflammation is a key factor modulating Ahr expression. Furthermore, kynurenine activation of Ahr is observed to stimulate expression of the enzyme IDO1, which generates kynurenine by degrading tryptophan, representing a positive feedback loop that may link inflammation with ROS production. On the other hand, the antioxidant Nrf2 can be stimulated by Ahr, and Nrf2 can itself activate Ahr expression. The balance between pro- and antioxidant functions of Ahr mediated by kynurenine may therefore regulate healthy versus unhealthy aging in different tissues and organ systems. Potential therapeutic approaches to target this pathway include exercise to alter kynurenine production or molecules such as metformin or resveratrol that may suppress Ahr activity.

  • Tractography of the external capsule and cognition: A diffusion MRI study of cholinergic fibers
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-25
    Geneviève Nolze Charron, Raphaël Dufort Rouleau, Jean-Christophe Houde, Matthieu Dumont, Christian-Alexandre Castellano, Stephen Cunanne, Dominique Lorrain, Tamàs Fülöp, Maxime Descoteaux, Christian Bocti

    Introduction White matter changes in the cholinergic tracts contribute to executive dysfunction in the context of cognitive aging. Lesions in the external capsule have been associated with executive dysfunction. The objectives of this study were to: 1) Characterize the lateral cholinergic tracts (LCT) and the superior longitudinal fasciculus (SLF). 2) Evaluate the association between the obtained diffusion measures and cognitive performance. Methods Neuropsychological testing and high angular resolution diffusion imaging (HARDI) of 34 healthy elderly participants was done, followed by anatomically constrained probabilistic tractography reconstruction robust to crossing fibers. The external capsule was manually segmented on a mean T1 image then merged with an atlas, allowing extraction of the LCT. Diffusion tensor imaging (DTI) and HARDI-based measures were obtained. Results Correlations between diffusion measures in the LCT and the time of completion of Stroop (left LCT radial and medial diffusivity), the Symbol Search score (right LCT apparent fiber density) and the motor part of Trail-B (left LCT axial and radial diffusivity) were observed. Correlations were also found with diffusion measures in the SLF. Discussion DTI and HARDI, with isolation of strategic white matter tracts for cognitive functions, represent complimentary tools to better understand the complex process of brain aging.

  • The potential mechanism of postoperative cognitive dysfunction in older people
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-23
    Xianyi Lin, Yeru Chen, Piao Zhang, Gang Chen, Youfa Zhou, Xin Yu

    Postoperative cognitive dysfunction (POCD) is a common disorder following surgery, which seriously threatens the quality of patients' life, especially the older people. Accumulating attention has been paid to POCD worldwide in pace with the popularization of anesthesia/surgery. The development of medical humanities and rehabilitation medicine sets higher demands on accurate diagnosis and safe treatment system of POCD. Although the research on POCD is in full swing, underlying pathogenesis is still inconclusive due to these conflicting results and controversial evidence. Generally, POCD is closely related to neuropsychiatric diseases such as dementia, depression and Alzheimer's disease in molecular pathways. Researchers have come up with various hypotheses to reveal the mechanisms of POCD, including neuroinflammation, oxidative stress, autophagy disorder, impaired synaptic function, lacking neurotrophic support, etc. Recent work focused on molecular mechanism of POCD in older people has been thoroughly reviewed and summed up here, concerning the changes of peripheral circulation, pathological pathways of central nervous system (CNS), the microbiota-gut-brain axis and the related brain regions. Accordingly, this article provides a better perspective to understand the development situation of POCD in older people, which is conductive to uncover the pathological mechanism and exploit reasonable treatment strategy of POCD.

  • Regulatory role of exercise-induced autophagy for sarcopenia
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-22
    Jiling Liang, Zhengzhong Zeng, Ying Zhang, Ning Chen

    Sarcopenia is an aging-related disease, described as the progressive reduction in mass and strength of skeletal muscle. Sarcopenia is typically characterized as the accumulation of damaged products due to an imbalance between protein synthesis and protein degradation. This imbalance between protein synthesis and degradation is attributed to impaired autophagic signal pathways. Sarcopenia can predispose elderly patients to several complications that may significantly impact patient quality of life. Recent evidence indicates that autophagy is required for the control of skeletal muscle mass under catabolic conditions and plays a crucial role in maintaining the homeostasis and integrity of skeletal muscle, specifically at appropriate level of autophagy. Exercise may be considered as a stress stimulus that can substantially modulate cellular signaling to promote metabolic adaptations. Appropriate exercise can induce autophagy or regulate the functional status of autophagy. Additionally, exercise-induced autophagy is the most effective treatment available in slowing down sarcopenia, improving mitochondrial quality, and the number of quiescent satellite cells, as a process that depends on basal autophagy. The molecular mechanisms underpinning the development of sarcopenia, however, remained largely unknown. In this narrative review, the current molecular mechanisms of sarcopenia are discussed from the perspective of exercise-induced autophagy and the effect of different exercise modalities on this response. This narrative review will aim to provide the references for developing scientific and optimal intervention strategies including exercise intervention for the prevention and treatment of sarcopenia through regulating autophagic signal pathways.

  • Clinical insights into the kynurenine pathway in age-related diseases
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-22
    Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh

    Accumulating evidence from diverse experiments, including heterochronic parabiosis—the surgical joining of two animals of different ages—has highlighted the importance of systemic factors in the progressive functional decline of various organs and tissues during aging. The major metabolic pathway of tryptophan, an essential amino acid in humans, is the kynurenine pathway (KP) in which indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the conversion of tryptophan into kynurenine. Importantly, circulating kynurenine produced by this enzymatic breakdown, as a primary driver of the aging process, has been linked to higher mortality in humans. This review discusses the potential roles of tryptophan derivatives as biomarkers for the risk of frailty in the elderly, based on human observational studies as well as the KP as a therapeutic target for age-related diseases.

  • Hypolipidemic effect of pure total flavonoids from peel of Citrus (PTFC) on hamsters of hyperlipidemia and its potential mechanism
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-21
    Yun Ling, Zheng Shi, Xingliang Yang, Zhaowei Cai, Lixia Wang, Xuming Wu, Aiqin Ye, Jianping Jiang

    Citrus is a group of popular fruit that includes oranges, lemons, limes and grapefruit but research of its peel on hyperlipidemia and its mechanism is rare reported. We examined the effect of pure total flavonoids from peel of Citrus (PTFC), an extract from the peel of Citrus Changshan-huyou which is a popular fruit in China, on hamsters with hyperlipoidemia induced by high-fat diet (HFD). We found that PTFC significantly reduced levels of serum cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) and improved levels of alanine transaminase (ALT), aspartate transaminase (AST) and Alkaline phosphatase (ALP) which associated with liver function in golden hamsters. Liver pathological results confirmed that the liver pathological section of golden hamster treated with PTFC was significantly improved compared with that of HFD group. The content of main cholesterol metabolic enzymes Cholesterol 7a-hydroxylase (CYP7A1) in liver was obviously recovered with PTFC treatment. Further studies shown that PTFC attenuated oxidative stress and free radical damage through superoxide dismutase (SOD) and malonyldialdehyde (MDA) tests and inflammatory injury by levels of Tumor Necrosis Factor-alpha (TNF-α) and interleukin-6 (IL-6) both in serum and hepatocyte of golden hamsters. Moreover, PTFC increased levels of RNA and protein expression of Peroxisome proliferator-activated receptor-α (PPAR-α) and PPAR-γ in liver, fat and skeletal muscle of hyperlipidemia golden hamster, significantly. Our results suggested that PTFC could play a hypolipidemic role through improvement of liver function by antioxidant and anti-inflammatory effects in hyperlipoidemia hamsters, its mechanism of action may through activating of PPARα and PPARγ.

  • Gait speed as predictor of transition into cognitive impairment: Findings from three longitudinal studies on aging
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-18
    Emiel O. Hoogendijk, Judith J.M. Rijnhart, Johan Skoog, Annie Robitaille, Ardo van den Hout, Luigi Ferrucci, Martijn Huisman, Ingmar Skoog, Andrea M. Piccinin, Scott M. Hofer, Graciela Muniz Terrera

    Objectives Very few studies looking at slow gait speed as early marker of cognitive decline investigated the competing risk of death. The current study examines associations between slow gait speed and transitions between cognitive states and death in later life. Methods We performed a coordinated analysis of three longitudinal studies with 9 to 25 years of follow-up. Data were used from older adults participating in H70 (Sweden; n = 441; aged ≥70 years), InCHIANTI (Italy; n = 955; aged ≥65 years), and LASA (the Netherlands; n = 2824; aged ≥55 years). Cognitive states were distinguished using the Mini-Mental State Examination. Slow gait speed was defined as the lowest sex-specific quintile at baseline. Multistate models were performed, adjusted for age, sex and education. Results Most effect estimates pointed in the same direction, with slow gait speed predicting forward transitions. In two cohort studies, slow gait speed predicted transitioning from mild to severe cognitive impairment (InCHIANTI: HR = 2.08, 95%CI = 1.40–3.07; LASA: HR = 1.33, 95%CI = 1.01–1.75) and transitioning from a cognitively healthy state to death (H70: HR = 3.30, 95%CI = 1.74–6.28; LASA: HR = 1.70, 95%CI = 1.30–2.21). Conclusions Screening for slow gait speed may be useful for identifying older adults at risk of adverse outcomes such as cognitive decline and death. However, once in the stage of more advanced cognitive impairment, slow gait speed does not seem to predict transitioning to death anymore.

  • The “Metabolic biomarkers of frailty in older people with type 2 diabetes mellitus” (MetaboFrail) study: Rationale, design and methods
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-18
    Riccardo Calvani, Leocadio Rodriguez-Mañas, Anna Picca, Federico Marini, Alessandra Biancolillo, Olga Laosa, Laura Pedraza, Jacopo Gervasoni, Aniello Primiano, Alfredo Miccheli, Isabelle Bourdel-Marchasson, Sophie C. Regueme, Roberto Bernabei, Emanuele Marzetti, Alan J. Sinclair, Giovanni Gambassi

    Type 2 diabetes mellitus (T2DM) is a leading cause of disability globally. Frailty is a high-impact geriatric condition that increases the risk of negative health outcomes and imposes remarkable health and social burden. Both frailty and T2DM show multifaceted pathophysiology, phenotypic heterogeneity, and fluctuating manifestations that challenge their management, especially when the two conditions co-occur. Muscle wasting and its correlates (e.g., metabolic perturbations and functional decline) that underlie frailty may exacerbates clinical manifestations of T2DM in older people, resulting in worse prognosis. The intrinsic complexity of frailty and T2DM has hampered the identification of clinically meaningful biomarkers to track the clinical progression of the two conditions over time and to monitor the efficacy of pharmacological and lifestyle interventions. Here, we propose an innovative approach for biomarker identification that couples multi-platform analytical determinations with chemometric modeling strategies. This novel multi-marker discovery process is described in the context of “Metabolic biomarkers of frailty in older people with type 2 diabetes mellitus” (MetaboFrail) study that aimed at identifying metabolic biomarkers of frailty in functionally limited older persons with T2DM.

  • Collagens and elastin genetic variations and their potential role in aging-related diseases and longevity in humans
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-15
    Roman Romero-Ortuno, Rose Anne Kenny, Ross McManus

    Collagens and elastin are ‘building blocks’ of tissues and extracellular matrix. Mutations in these proteins cause severe congenital syndromes. Adverse genetic variations may accelerate the aging process in adults contributing to premature morbidity, disability and/or mortality. Favorable variants may contribute to longevity and/or healthy aging, but this is much less studied. We reviewed the association between variation in the genes of collagens and elastin and premature aging, accelerated aging, age-related diseases and/or frailty; and the association between genetic variation in those and longevity and/or healthy aging in humans. A systematic search was conducted in MEDLINE and other online databases (OMIM, Genetics Home Reference, Orphanet, ClinVar). Results suggest that genetic variants lead to aging phenotypes of known congenital disease, but also to association with common age-related diseases in adults without known congenital disease. This may be due to the variable penetrance and expressivity of many variants. Some collagen variants have been associated with longevity or healthy aging. A limitation is that most studies had <1000 participants and their criterion for statistical significance was p < 0.05. Results highlight the importance of adopting a lifecourse approach to the study of the genomics of aging. Gerontology can help with new methodologies that operationalize biological aging.

  • Effects of age on feeding response: Focus on the rostral C1 neuron and its glucoregulatory proteins
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-06
    Hajira Ramlan, Hanafi Ahmad Damanhuri

    Background Older people are likely to develop anorexia of aging. Rostral C1 (rC1) catecholaminergic neurons in rostral ventrolateral medulla (RVLM) are recently discovered its role in food intake control. It is well established that these neurons regulate cardiovascular function. Objective This study aims to determine the effect of age on the function of rostral C1 (rC1) neurons in mediating feeding response. Method Male Sprague Dawley rats at 3-months (n = 22) and 24-months (n = 22) old were used and further divided into two subgroups; 1) treatment group with 2-deoxy-d-glucose (2DG) and 2) vehicle group. Feeding hormones such as cholecystokinin (CCK), ghrelin and leptin were analysed using enzyme-linked immunosorbent assay (ELISA). Rat brain was carefully dissected to obtain the brainstem RVLM region. Further analysis was carried out to determine the level of proteins and genes in RVLM that were associated with feeding pathway. Protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK) and neuropeptide Y Y5 receptor (NPY5R) were determined by western blot. Expression of TH, AMPK and NPY genes were determined by real-time PCR. Results This study showed that blood glucose level was elevated in young and old rats following 2DG administration. Plasma CCK-8 concentration was higher in the aged rats at basal and increased with 2DG administration in young rats, but the leptin and ghrelin showed no changes. Old rats showed higher TH and lower AMPK mRNA levels. Glucoprivation decreased AMPK mRNA level in young rats and decreased TH mRNA in old rats. Aged rC1 neurons showed higher NPY5R protein level. Following glucoprivation, rC1 neurons produced distinct molecular changes across age in which, in young rats, AMPK phosphorylation level was increased and in old rats, TH phosphorylation level was increased. Conclusion These findings suggest that glucose-counterregulatory responses by rC1 neurons at least, contribute to the ability of young and old rats in coping glucoprivation. Age-induced molecular changes within rC1 neurons may attenuate the glucoprivic responses. This situation may explain the impairment of feeding response in the elderly.

  • The multiple faces of tryptophan in bone biology
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-06
    Ahmed Al Saedi, Shilpa Sharma, Matthew A. Summers, Kulmira Nurgali, Gustavo Duque

    Osteoporosis is highly prevalent in older persons. While many advances have been made in the field of osteoporosis, current treatments have been affected by unexpected side effects and limited efficacy; therefore, new approaches to identify disease mechanisms and pathways are required. This review focuses on the influence of tryptophan metabolites, particularly kynurenines and serotonin on bone. The kynurenine (KYN) pathway is associated with osteoblastogenesis and can be linked to the pathophysiology of osteoporosis. The activity of osteoblasts is reduced by 3-hydroxykynurenine (3-HKYN), a product of KYN. In addition, decreasing concentrations of 3-hydroxyanthranilic acid with aging can be one of the causes of bone loss. In contrast, picolinic acid, an end-product of the KYN pathway, acts as a bone anabolic. On the other hand, gut-derived serotonin (GDS) inhibits bone formation, whereas brain-derived serotonin enhances bone formation and decreases bone resorption. Overall, understanding the exact mechanisms of action of tryptophan metabolites on bone could have great potential to develop effective treatments for osteoporosis and other bone diseases.

  • Kynurenine pathway and human systems
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-05
    Abdulla A.-B. Badawy

    The essential amino acid L-tryptophan (Trp) appears to play an important role in aging by acting as a general regulator of protein homeostasis. The major route of Trp degradation, the kynurenine pathway (KP), produces a range of biologically active metabolites that can impact or be impacted by a variety of body systems, including the endocrine, haemopoietic, immune, intermediary metabolism and neuronal systems, with the end product of the KP, NAD+, being essential for vital cellular processes. An account of the pathway, its regulation and functions is presented in relation to body systems with a summary of previous studies of the impact of aging on the pathway enzymes and metabolites. A low-grade inflammatory environment characterized by elevation of cytokines and other immune modulators and consequent disturbances in KP activity develops with aging. The multifactorial nature of the aging process necessitates assessment of factors determining the progression of this mild dysfunction to age-related diseases and developing strategies aimed at arresting and reversing this progression.

  • 17α-Estradiol promotes ovarian aging in growth hormone receptor knockout mice, but not wild-type littermates
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-04
    José V.V. Isola, Bianka M. Zanini, Silvana Sidhom, John J. Kopchick, Andrzej Bartke, Michal M. Masternak, Michael B. Stout, Augusto Schneider

    Growth hormone receptor knockout mice (GHRKO) have reduced body size and increased insulin sensitivity. These mice are known for having extended lifespan, healthspan and female reproductive longevity. Seventeen α-estradiol (17α-E2) is reported to increase insulin sensitivity and extend lifespan in male mice, with less robust effects in female mice. The aim of this study was to evaluate the ovarian reserve in wild type and GHRKO mice treated with 17α-E2. The mice were divided into four groups, GHRKO mice receiving a standard chow diet, GHRKO mice treated 17α-E2, wild type mice receiving a standard chow diet and WT mice treated with 17α-E2. 17α-E2 was provided in the diet for four months. IGF1 plasma concentrations and changes in body weight were assessed. Histological slides were prepared from the ovaries and the number of follicles was counted. GHRKO mice receiving the control diet had a greater number of primordial follicles and lower numbers of primary follicles compared to the other groups (p < 0.05). 17α-E2 treatment decreased the number of primordial follicles in GHRKO mice (p < 0.05), however had no effect in wild type mice. Treatment with 17α-E2 had no significant effect on the change in body weight during the experiment (p = 0.75). Plasma IGF1 concentrations were significantly lower in GHRKO mice as compared to wild type. In conclusion, we found that GHRKO mice displayed lesser primordial follicle activation as compared to wild type mice, but this phenotype was reversed by 17α-E2 administration, suggesting that ovarian aging is increased by 17α-E2 in long-living mice with extended reproductive longevity.

  • Exploring the potential of salivary and blood immune biomarkers to elucidate physical frailty in institutionalized older women
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-10-31
    Guilherme Eustáquio Furtado, Matheus Uba-Chupel, Luciele Minuzzi, Miguel Patrício, Marisa Loureiro, Stephan Bandelow, Eef Hogervorst, José Pedro Ferreira, Ana Maria Teixeira

    Identification of older populations at increased risk of physical frailty using biochemical approaches could improve screening accuracy. The aim of this study was to study the relationship between immune markers and independent components of physical frailty in institutionalized older women. A sample of 358 institutionalized-dwelling women, aged 75 years and older, were assessed for biosocial factors and general health status, pro and anti-inflammatory cytokines, sex steroid hormones, salivary anti-microbial proteins, blood cells counts and the five Fried's physical frailty components that allowed for classification of the sample into frail, prefrailty and not-frail subgroups. Results showed that cytokines IL-6, IL-10, IL-1β, TNF-α, and the TNF-α/IL-10 ratio, mean corpuscular haemoglobin, salivary cortisol and α-amylase were all associated with frailty. Weakness and Exhaustion were the frailty components that were most strongly associated with these biomarkers. Salivary α-amylase was the biomarker that best explained frailty, as it was associated with all five components of physical frailty, and could be used as a potential screening tool. Future research needs to investigate the causal-effect association between salivary innate immune makers, susceptibility to infection and frailty.

  • Skeletal muscle fat in individuals with rheumatoid arthritis compared to healthy adults
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-10-31
    Samannaaz S. Khoja, Charity G. Patterson, Bret H. Goodpaster, Anthony Delitto, Sara R. Piva

    Objective To compare skeletal muscle fat (SMF), intermuscular adipose tissue (IMAT) and subcutaneous adipose tissue (SAT) between individuals with rheumatoid arthritis (RA), and healthy individuals of the same age, and healthy individuals at least 10 years older than those with RA. Methods Two cross-sectional studies. In the first study, RA subjects were matched by age, sex, and BMI with healthy adults. In the second, RA subjects were matched by sex and BMI to adults 10–20 years older. SMF, IMAT and SAT were measured with Computed Tomography images of the mid-thigh region. We used parametric or non-parametric related-samples tests to compare fat accumulation between RA subjects and healthy adults. Results In the first study SMF was significantly higher in the RA cohort compared to their age-matched healthy counterparts (mean difference = −3.5 HU (95% −6.2, −0.9), p = 0.011), but IMAT and SAT were similar between cohorts. In the second study, SMF, IMAT and SAT were not significantly different between the RA and matched older healthy cohorts. In both studies, there were no significant differences in mid-thigh muscle area between RA subjects and healthy adults. Conclusion SMF accumulation in RA was higher than in healthy individuals of similar age, sex, BMI. Accumulation of fat within and around the muscles in RA was not different compared to the matched healthy older individuals, indicating that muscle fat accumulation in RA might mimic a pattern not different from healthy aging.

  • Biomarkers in the path from cellular senescence to frailty.
    Exp. Gerontol. (IF 3.080) Pub Date : 2019-11-05
    Marta Zampino,Luigi Ferrucci,Richard D Semba

  • Hesperidin reverses perivascular adipose-mediated aortic stiffness with aging.
    Exp. Gerontol. (IF 3.080) Pub Date : 2017-08-07
    An Ouyang,Tyler B Garner,Bradley S Fleenor

    We tested the hypothesis that hesperidin would reverse age-related aortic stiffness, perivascular adipose (PVAT) mediated-arterial stiffening and PVAT advanced glycation end-products (AGE) accumulation. Aortic pulse wave velocity (aPWV) and intrinsic mechanical stiffness, two measures of arterial stiffness, were assessed in C57BL/6 mice that were young (6months), old (27-29months), or old treated with hesperidin for 4weeks. Old compared with young mice had increased aPWV (444±10 vs. 358±8cm/s, P<0.05) and mechanical stiffness (6506±369 vs. 3664±414kPa, P<0.05). In old mice hesperidin reduced both aPWV (331±38cm/s) and mechanical stiffness (4445±667kPa) to levels not different from young. Aortic segments from old animals cultured with (+) PVAT had greater mechanical stiffness compared to young (+) PVAT (6454±323 vs. 3575±440kPa, P<0.05) that was ameliorated in arteries from old hesperidin treated cultured (+) PVAT (2639±258kPa). Hesperidin also reversed the aging-related PVAT AGE accumulation (all, P<0.05). A 4-week treatment with the AGE inhibitor aminoguanidine reversed both the age-related increase in aPWV (390±7cm/s) and mechanical stiffness (3396±1072kPa), as well as mechanical stiffness in arteries cultured (+) PVAT (3292±716kPa) (all, P<0.05) to values not different from young. In conclusion, hesperidin ameliorates the age-related increase in aortic stiffness and the PVAT-mediated effects on arterial stiffening. Hesperidin also reversed PVAT AGE accumulation, where PVAT AGE were shown to promote aortic stiffness with aging.

  • 更新日期:2019-11-01
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