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  • Age- and sex-specific changes in lower-limb muscle power throughout the lifespan
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-16
    Alcazar J, Aagaard P, Haddock B, et al.

    BackgroundOur main goal was to evaluate the pattern and time course of changes in relative muscle power and its constituting components throughout the lifespan. MethodsA total of 1305 subjects (729 women and 576 men; aged 20-93 years) participating in the Copenhagen Sarcopenia Study took part. Body mass index (BMI), leg lean mass assessed by DXA, and leg extension muscle power (LEP) assessed by the Nottingham power rig were recorded. Relative muscle power (normalized to body mass) and specific muscle power (normalized to leg lean mass) were calculated. Segmented regression analyses were used to identify the onset and pattern of age-related changes in the recorded variables. ResultsRelative muscle power began to decline above the age of 40 in both women and men, with women showing an attenuation of the decline above 75 years. Relative muscle power decreased with age due to i) the loss of absolute LEP after the fourth decade of life and ii) the increase in BMI up to the age of 75 years in women and 65 years in men. The decline in absolute LEP was caused by a decline in specific LEP up to the age of 75 in women and 65 in men, above which the loss in relative leg lean mass also contributed. ConclusionsRelative power decreased i) above 40 years by the loss in absolute power (specific power only) and the increase in body mass, and ii) above ̴ 70 years by the loss in absolute power (both specific power and leg lean mass).

    更新日期:2020-01-16
  • Longitudinal Association Between Energy Regulation and Fatigability in Mid-to-Late Life
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-14
    Schrack J, Wanigatunga A, Zipunnikov V, et al.

    BackgroundDeficits in energy production and utilization have been linked to higher fatigue and functional decline with aging. Lesser known is whether individuals with a combination of low peak energy capacity and high energy costs for mobility (e.g., impaired energy regulation) are more likely to experience the onset and progression of high fatigability with aging. MethodsParticipants in the Baltimore Longitudinal Study of Aging (n = 651, 49.0% male, mean age 71.9, range 50-94) with >2 visits who completed fatigability (Borg RPE after a 5-min 1.5mph treadmill walk), slow walking energy expenditure (VO2 ml/kg/min), and peak walking energy expenditure (VO2 ml/kg/min), testing between 2007-2018. The longitudinal association between each measure of energy expenditure, a ratio of energy cost-to-capacity, and perceived fatigability was modeled using mixed effects models adjusted for age, body composition, and comorbidities. Time to higher perceived fatigability (RPE>10) was modeled using Cox proportional hazards models. ResultsIn continuous analyses higher slow walking energy expenditure (p<.05) and a higher cost ratio (p<.001) were associated with greater perceived fatigability over time. Cox proportional hazards models using tertiles of the cost ratio suggest that, compared to those in the lowest tertile, those in the middle and highest tertiles had 1.89 (95% CI:1.57–5.16) and 2.85 (95% CI:1.05 – 3.40) times greater risk of developing higher fatigability, respectively. ConclusionFindings suggest that strategies to prevent fatigability should consider methods to improve energy regulation by targeting both the independent and combined effects of declining peak capacity and rising energy costs for mobility with aging.

    更新日期:2020-01-15
  • Trends in physical and cognitive performance among community-dwelling older adults in Switzerland
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-14
    Henchoz Y, Büla C, von Gunten A, et al.

    BackgroundWith population aging, a key question is whether new cohorts of older people are in better health than previous ones. This study aimed to compare the physical and cognitive performance of community-dwelling older adults assessed at similar age in 2005, 2010, and 2015. MethodsThis repeated cross-sectional analysis used data from the Lausanne cohort 65+, a three random sample population-based study. Performance of participants aged 66–71 years in 2005 (N=1309), 2010 (N=1253) and 2015 (N=1328) was compared using a battery of six physical and four cognitive tests. Analyses included tests for trend across samples and multivariable linear regression models. ResultsAdjusted performance in all four timed physical tests (gait speed, Timed Up-and-Go, five times chair stand, and Moberg Picking-Up) improved across samples from 2005 to 2015, by +12.7% (95% CI +10.5%; +14.9%) to +20.4% (95% CI +17.7%; +23.0%) in females, and by +10.6% (95% CI +8.7%; +12.4%) to +16.7% (95% CI +13.4%; +20.0%) in males. In contrast, grip strength and balance did not improve across samples. Adjusted cognitive performance showed no change in the Trail Making Test, but worsened significantly across samples for the Mini-Mental State Examination, verbal fluency, and the clock drawing test in both females (1.9% (95% CI 2.7%; 1.1%) to 6.7% (95% CI 8.9%; 4.6%)) and males (2.5% (95% CI 3.4%; 1.6%) to 8.0% (95% CI 11.1%; 4.9%)). ConclusionsOver the last decade, performance of adults aged 66–71 years improved significantly in timed physical tests but worsened in most cognitive measures among later-born samples.

    更新日期:2020-01-15
  • Accelerometer-measured sedentary and physical activity time and their correlates in European older adults: The SITLESS study
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-14
    Giné-Garriga M, , Sansano-Nadal O, et al.

    BackgroundSedentary behavior (SB) and physical activity (PA) are important determinants of health in older adults. This study aimed to describe the composition of accelerometer-measured SB and PA in older adults, to explore self-reported context-specific SB, and to assess socio-demographic and functional correlates of engaging in higher levels of SB in participants of a multi-center study including four European countries. Methods1360 community-dwelling older adults from the SITLESS study (61.8% women; 75.3±6.3 years) completed a self-reported SB questionnaire and wore an ActiGraph accelerometer for seven days. Accelerometer-determined compositional descriptive statistics were calculated. A fixed effects regression analysis was conducted to assess the socio-demographic (country, age, sex, civil status, education and medications) and functional (BMI and gait speed) correlates. ResultsOlder adults spent 78.8% of waking time in SB, 18.6% in light-intensity PA (LPA), and 2.6% in moderate to vigorous PA (MVPA). Accelerometry showed that women engaged in more LPA and walking and men engaged in higher amounts of MVPA. Watching television and reading accounted for 47.2% of waking time. Older age, being a man, single, taking more medications, being obese and overweight, and having a slower gait speed were statistically significant correlates of more sedentary time. ConclusionsThe high amount of SB of our participants justifies the need to develop and evaluate interventions to reduce sitting time. A clinically relevant change in gait speed can decrease almost 0.45 percentage points of sedentary time. The distribution of context-specific sedentary activities by country and sex showed minor differences, albeit worth noting.

    更新日期:2020-01-15
  • High levels of physical activity in later life are associated with enhanced markers of mitochondrial metabolism
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-14
    Joanisse S, Ashcroft S, Wilkinson D, et al.

    The age-associated reduction in muscle mass is well characterised, however less is known regarding the mechanisms responsible for the decline in oxidative capacity also observed with advancing age. The purpose of the current study was therefore to compare mitochondrial gene expression and protein content between young and old recreationally active, and older highly active individuals. Muscle biopsies were obtained from the vastus lateralis of young males (YG: 22±3 years) and older (OG: 67±2 years) males not previously engaged in formal exercise and older male master cyclists (OT: 65±5 years) who had undertaken cycling exercise for 32±17 yrs. Comparison of gene expression between YG, OG and OT groups revealed greater expression of mitochondrial-related genes, namely electron transport chain (ETC) complexes II, III, IV (p<.05) in OT compared to YG and OG. Gene expression of mitofusion (MFN)-1/2, mitochondrial fusion genes, were greater in OT compared to OG (p<.05). Similarly, protein content of ETC complexes I, II and IV were significantly greater in OT compared to both YG and OG (p<.001). Protein content of peroxisome proliferator-activated receptor gamma, coactivator 1 α (PGC-1α), was greater in OT compared to YG and OG (p<.001). Our results suggest that the aging process per se, is not associated with a decline in gene expression and protein content of ETC complexes. Mitochondrial-related gene expression and protein content is substantially greater in OT, suggesting that exercise-mediated increases in mitochondrial content can be maintained into later life.

    更新日期:2020-01-15
  • Socioeconomic Inequalities in Disability-free Life Expectancy in Older People from England and the United States: A Cross-national Population-Based Study
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-15
    Zaninotto P, Batty G, Stenholm S, et al.

    BackgroundWe examined socioeconomic inequalities in disability-free life expectancy in older men and women from England and the United States and explored whether people in England can expect to live longer and healthier lives than those in the United States. MethodsWe used harmonized data from the Gateway to Global Aging Data on 14,803 individuals aged 50+ from the U.S. Health and Retirement Study (HRS) and 10,754 from the English Longitudinal Study of Ageing (ELSA). Disability was measured in terms of impaired activities and instrumental activities of daily living. We used discrete-time multistate life table models to estimate total life expectancy and life expectancy free of disability. ResultsSocioeconomic inequalities in disability-free life expectancy were of a similar magnitude (in absolute terms) in England and the United States. The socioeconomic disadvantage in disability-free life expectancy was largest for wealth, in both countries: people in the poorest group could expect to live seven to nine fewer years without disability than those in the richest group at the age of 50. ConclusionsInequalities in healthy life expectancy exist in both countries and are of similar magnitude. In both countries, efforts in reducing health inequalities should target people from disadvantaged socioeconomic groups.

    更新日期:2020-01-15
  • Relationship between Changes in Sedative Hypnotic Medications Burden and Cognitive Outcomes in Hospitalized Older Adults
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-14
    Smichenko J, Gil E, Zisberg A.

    BackgroundSedative-hypnotic medications (SHM) are frequently used in hospitalized older patients, despite undesirable effects on cognitive status. Although previous studies found a significant number of patients experience changes in SHM use during hospitalization, it is unclear which pattern of change leads to hospital acquired cognitive decline (HACD). This study tested the association between patterns of SHM change and HACD. MethodsThis secondary analysis study included 550 patients age 70+ who were cognitively intact at admission (Short Portable Mental Status Questionnaire (SPMSQ) ≥8). HACD was defined as at least 1-point decline in SPMSQ between admission and discharge. Changes in sedative burden (SB) before and during hospitalization (average SB of all hospitalization days) were coded using the Drug Burden Index (DBI) sorting study participants into four groups: without SB (n=254), without SB changes (n=132), increased SB (n=82), and decreased SB (n=82). ResultsIncidence of HACD was 233/550 (42.4%). In multivariate logistic analysis controlling for demographic characteristics, length of stay, severity of acute illness, comorbidity, SB-score at home, and depression, the odds of HACD were 2.45 (95% CI:1.16-5.13) among participants with increased SB, 2.10 (95% CI: 1.13-3.91) among participants without SB changes, compared to participants with decreased SB. ConclusionOlder patients whose sedative burden is increased or does not change are at higher risk for acquired cognitive decline than are those whose sedative burden is reduced. Identifying patients with a potential increase in sedative burden and intervening to reduce it may help to fight hospital acquired cognitive decline.

    更新日期:2020-01-14
  • Vitamin D status of adults in the community, in outpatient clinics, in hospital and in nursing homes in the West of Ireland
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-14
    Griffin T, Wall D, Blake L, et al.

    BackgroundApproximately 1 billion people worldwide have Vitamin D deficiency. The aim of this study was to compare Vitamin D status and serum 25-hydroxyvitamin D (25(OH)D) concentrations among adults sampled in the community, in outpatient clinics, as hospital inpatients and in nursing homes in the West of Ireland. The secondary aim was to determine the associations between length of hospital stay (inpatients) at time of serum 25(OH)D sampling and Vitamin D status. MethodsA cross-sectional study was carried out. Patients who had serum 25(OH)D analysis carried out in Galway University Hospitals (January 2011-December 2015) were identified following interrogation of the electronic laboratory data system. Baseline demographics, location and date of sample collection were recorded. Vitamin D deficiency was defined as a serum 25(OH)D concentration<25nmol/L. ResultsIn total, 24,302 patient samples were eligible for inclusion: community n=15,319; outpatient clinics n=6,371; inpatients n=2,339; nursing home residents n=273. Vitamin D deficiency was more common in nursing home residents than inpatients, or those sampled in outpatient clinics or in the community (42%-v-37%-v-17%-v-13%; p<0.001). Inpatients sampled further into their hospital stay (≥3days) had greater Vitamin D deficiency than inpatients sampled on 0-2 days (p=0.007). Season(p<0.001), sex(p<0.001) and age(p<0.001) were associated with 25(OH)D concentrations. Vitamin D deficiency was more common in Winter/Spring, in males and in those aged ≥80years. ConclusionsNursing home residents and inpatients are at the highest risk for Vitamin D deficiency. Season, sex, age and day of hospital stay on which serum 25(OH)D concentrations were sampled were associated with Vitamin D status.

    更新日期:2020-01-14
  • Adolescence and aging: impact of adolescence inflammatory stress and microbiota alterations on brain development, aging and neurodegeneration
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-10
    Yahfoufi N, Matar C, Ismail N.

    Puberty/adolescence is a critical phase during neurodevelopment with numerous structural, neurochemical, and molecular changes occurring in response to genetic and environmental signals. A consequence of this major neuronal reorganizing and remodelling, is a heightened level of vulnerability to stressors and immune challenge. The gut microbiota is a fundamental modulator of stress and immune responses and has been found to play a role in mental health conditions and neurodegenerative disorders. Environmental insults (stress, infection, neuroinflammation, use of antibiotics) during adolescence can result in dysbiosis subsidizing the development of brain disorders later in life. Also, pubertal neuroinflammatory insults can alter neurodevelopment, impact brain functioning in an enduring manner, and contribute to neurological disorders related to brain aging such as Alzheimer’s disease, Parkinson’s disease and depression. Exposure to probiotics during puberty can mitigate inflammation, reverse dysbiosis and decrease vulnerabilities to brain disorders later in life. The goal of this review is to reveal the consequences of pubertal exposure to stress and immune challenges on the gut microbiota, immune reactivity within the brain and the risk or resilience to stress-induced mental illnesses and neurodegenerative disorders. We propose that consumption of probiotics during adolescence contribute to the prevention of brain pathologies in adulthood.

    更新日期:2020-01-13
  • Are Advances in Survival among the Oldest Old Seen across the Spectrum of Health and Functioning?
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-13
    Thinggaard M, Jeune B, Osler M, et al.

    BackgroundMortality rates have been reduced by half over the last 60 years for nonagenarians, and the progress is continuing. The greater survival might be due to overtreatment of severely physically and cognitively disabled individuals which is a big concern for societies and individuals. MethodsThe study population comprised two Danish birth cohorts: the 1905 Cohort and the 1915 Cohort. At age 95, all from the two cohorts who were still alive and living in Denmark were invited to participate in a health survey that used the same assessment instrument. A total of 2,670 (56.8%) persons participated in the two surveys and survival was assessed through a 7.3-year follow-up period during which 2,497 (93.5%) had died, and with virtually no loss to follow-up. ResultsDespite the increasing chance of surviving to age 95, the 1915 Cohort had significantly better health and functioning than the 1905 Cohort. The survival advantage in the 1915 Cohort continued in the follow-up period after age 95: Median survival length was 2.4 months longer, P-value=0.011. This advantage was not statistically associated with different levels of activities of daily living, physical performance, cognitive functioning, self-rated health and life satisfaction. However, the advantage tended to be more pronounced among people with better health. ConclusionsLifespan and health increases among the oldest old. The improvement in survival for 95-year-olds born in 1915 compared to 1905 was seen across the whole spectrum of health and functioning, with a tendency towards bigger improvement among those in good health.

    更新日期:2020-01-13
  • Skeletal muscle energetics and mitochondrial function are impaired following 10 days of bed rest in older adults
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-07
    Standley R, Distefano G, Trevino M, et al.

    BackgroundOlder adults exposed to periods of inactivity during hospitalization, illness or injury lose muscle mass and strength. This, in turn, predisposes poor recovery of physical function upon re-ambulation and represents a significant health risk for older adults. Bed rest (BR) results in altered skeletal muscle fuel metabolism and loss of oxidative capacity that have recently been linked to the muscle atrophy program. Our primary objective was to explore the effects of BR on mitochondrial energetics in muscle from older adults. A secondary objective was to examine the effect of β-hydroxy-β-methylbuturate (HMB) supplementation on mitochondrial energetics. MethodsWe studied 20 older adults before and after a 10-day BR intervention, who consumed a complete oral nutritional supplement (ONS) with β-hydroxy-β-methylbuturate (HMB) (3.0g/d HMB, n=11) or without HMB (CON, n=9). Percutaneous biopsies of the vastus lateralis were obtained to determine mitochondrial respiration and H2O2 emisson in permeabilized muscle fibers along with markers of content. RNA sequencing and lipidomics analyses were also conducted. ResultsWe found a significant up-regulation of collagen synthesis and down-regulation of ribosome, oxidative metabolism and mitochondrial gene transcripts following BR in the CON group. Alterations to these gene transcripts were significantly blunted in the HMB group. Mitochondrial respiration and markers of content were both reduced and H2O2 emission was elevated in both groups following BR. ConclusionsIn summary, 10 days of bed rest in older adults causes a significant deterioration in mitochondrial energetics, while transcriptomic profiling revealed that some of these negative effects may be attenuated by an ONS containing HMB.

    更新日期:2020-01-07
  • Factors Associated with Insidious and Noninsidious Disability
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-07
    Gill T, Murphy T, Gahbauer E, et al.

    BackgroundAlthough disability is often precipitated by an illness/injury, it may arise insidiously. Our objectives were to identify the factors associated with the development of insidious and noninsidious disability and determine whether these risk factors differ between the two types of disability. MethodsWe prospectively evaluated 754 community-living persons, 70+ years, from 1998 to 2016. The unit of analysis was an 18-month person-interval, with risk factors assessed at the start of each interval. Disability in four activities of daily living and exposure to intervening events, i.e. illnesses/injuries leading to hospitalization, emergency department visits, or restricted activity, were assessed each month. Insidious and noninsidious disability were defined based on the absence and presence of an intervening event. ResultsThe rate of noninsidious disability (21.7%) was twice that of insidious disability (10.8%). In multivariable recurrent-event Cox analyses, six factors were associated with both disability outcomes: non-Hispanic white race, lower extremity muscle weakness, poor manual dexterity, and (most strongly) frailty, cognitive impairment, and low functional self-efficacy. Three factors were associated with only noninsidious disability (older age, number of chronic conditions, and depressive symptoms), while four were associated with only insidious disability (female sex, lives with others, low SPPB score, and upper extremity weakness). The modest differences in risk factors identified for the two outcomes in multivariable analyses were less apparent in the bivariate analyses. ConclusionsAlthough arising from different mechanisms, insidious and noninsidious disability share a similar set of risk factors. Interventions to prevent disability should prioritize this shared set of risk factors.

    更新日期:2020-01-07
  • Functional connectivity of the supplementary motor network is associated with Fried’s modified frailty score in the elderly
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-04
    Lammers F, Zacharias N, Borchers F, et al.

    Frailty is a geriatric syndrome defined by coexistence of unintentional weight loss, low physical reserve or activity and is associated with adverse health events. Neuroimaging studies reported structural white matter changes in frail patients. In the current study, we hypothesized that clinical frailty is associated also with functional changes in motion-related cortical areas, i. e. (pre-)supplementary motor areas (SMA, pre-SMA). We expected that observed functional changes are related to motor-cognitive test performance.We studied a clinical sample of 143 cognitively healthy patients ≥65 years presenting for elective surgery, enrolled in the BioCog prospective multicentric cohort study on postoperative cognitive disorders. Participants underwent preoperative resting-state fMRI, motor-cognitive testing and assessment of Fried’s modified frailty criteria. We analyzed functional connectivity associations with frailty and motor-cognitive test performance.Clinically robust patients (N=60) showed higher connectivity in the SMA network compared to frail (N=13) and pre-frail (N=70) patients. No changes were found in the pre-SMA network. SMA connectivity correlated with motor speed (Trail-Making-Test A) and manual dexterity (Grooved Pegboard Test).Our results suggest that diminished functional connectivity of the SMA is an early correlate of functional decline in the elderly. The SMA may serve as a potential treatment target in frailty.

    更新日期:2020-01-04
  • Bring Back the Rat!
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2020-01-02
    Carter C, Richardson A, Huffman D, et al.

    As 2020 is “The Year of the Rat” in the Chinese astrological calendar, it seems an appropriate time to consider whether we should bring back the laboratory rat to front-and-center in research on the basic biology of mammalian aging. Beginning in the 1970’s, aging research with rats became common, peaking in 1992 but then declined dramatically by 2018 as the mouse became pre-eminent. The purpose of this review is to highlight some of the historical contributions as well as current advantages of the rat as a mammalian model of human aging, because we suspect at least a generation of researchers is no longer aware of this history or these advantages. Herein, we compare and contrast the mouse and rat in the context of several biological domains relevant to their use as appropriate models of aging: phylogeny/domestication, longevity interventions, pathology/physiology, and behavior/cognition. It is not the goal of this review to give a complete characterization of the differences between mice and rats, but to provide important examples of why using rats as well as mice is important to advance our understanding of the biology of aging.

    更新日期:2020-01-02
  • Improved Human Muscle Biopsy Method To Study Neuromuscular Junction Structure And Functions With Aging
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-15
    Aubertin-Leheudre M, Pion C, Vallée J, et al.

    Reduced mobility and physical independence of elders has emerged as a major clinical and public health priority with extended life expectancy. The impact of the neuromuscular function on muscle activity and properties has emerged as a critical factor influencing the progress and outcome of muscle changes with aging. However, very little is known about the neuromuscular junctions (NMJs) in humans, in part due to technical constraints limiting the access to healthy, fresh neuromuscular tissue. Here we describe a method, called Biopsy using Electrostimulation for Enhanced NMJSampling (BeeNMJs) that improves the outcome of muscle biopsies.We used local cutaneous stimulation to identify the area enriched with NMJs for each participant at the right Vastus lateralis (VL). The needle biopsy was then performed in proximity of that point. The BeeNMJs procedure was safe for the participants. We observed NMJs in 53.3% of biopsies in comparison with only 16.7% using the traditional method. Furthermore, we observed an average of 30.13 NMJs per sample compared to only 2.33 for the traditional method. Importantly, high quality neuromuscular material was obtained whereby pre-, postsynaptic and glial elements were routinely labeled, simultaneously with myosin heavy chain type I. The BeeNMJs approach will facilitate studies of NMJs, particularly in human disease or aging process.

    更新日期:2019-12-20
  • Parental history of dementia is associated with increased small vessel cerebrovascular disease
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-15
    Stamm B, Lao P, Rizvi B, et al.

    BackgroundSmall vessel cerebrovascular dysfunction that manifests on MRI as white matter hyperintensities(WMH), is linked to increased risk and progression of Alzheimer’s disease(AD), but there is considerable debate about whether it represents a core feature of the disease. Parental history of dementia is a risk factor for AD, suggesting a strong heritable component; the examination of the extent to which parental history of dementia is associated with cerebrovascular disease could provide insight into the aggregation of AD and cerebrovascular disease. MethodsThis study included 481 community-dwelling older adults(mean age=74.07+5.81; 56% women) with available MRI scans. Participants were classified as having a parental history of dementia or having no parental history based on self-report. Total WMH values were calculated and compared between the two groups with general linear models, adjusting for relevant covariates. We also compared WMH volume between those with a reported sibling history of dementia and those without. ResultsOne hundred twelve participants reported having a parental history of dementia and 369 reported no parental history. Those with parental history had greater total WMH volume than those without(F=4.17,p=0.042,partial η2= 0.009). Results were strongest for those with maternal versus paternal history(F=2.43,p=0.089,partial η2= 0.010vs.<0.001) and among Hispanic(F=5.57,p=0.020,partial η2=0.038) and non-Hispanic White participants(F=4.17,p=0.042,partial η2=0.009). Those with reported sibling history of dementia did not differ from those without. ConclusionsOlder adults with parental, particularly maternal, history of dementia have increased WMH. The results highlight the possibility that cerebrovascular changes are a core feature of AD, as WMH severity and parental history aggregate together.

    更新日期:2019-12-20
  • Prevalence and loads of torquetenovirus (TTV) in the European MARK-AGE Study population
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-15
    Giacconi R, Maggi F, Macera L, et al.

    Torquetenovirus (TTV) viremia has been associated with increased mortality risk in the elderly population. This work aims to investigate TTV viremia as a potential biomarker of immunosenescence. We compared levels of circulating TTV in 1,813 participants of the MARK-AGE project, including human models of delayed (offspring of centenarians - GO) and premature (Down syndrome - DS) immunosenescence. The TTV load was positively associated with age, CMV antibody levels and the Cu/Zn ratio, and negatively associated with platelets, total cholesterol and total IgM. TTV viremia was highest in DS and lowest in GO, with intermediate levels in the SGO (spouses of GO) and RASIG (randomly recruited age-stratified individuals from the general population) populations.In the RASIG population, TTV DNA loads showed a slight negative association with CD3+T-cells and CD4+T-cells. Finally, males with ≥4log TTV copies/ml had a higher risk of having a CD4/CD8 ratio<1 than those with lower viremia (OR = 2.85, 95%CI: 1.06-7.62), as well as reduced CD3+ and CD4+T-cells compared to males with lower replication rates (<4log), even after adjusting for CMV infection.In summary, differences in immune system preservation are reflected in the models of delayed and premature immunosenescence, displaying the best and worst control over TTV replication, respectively. In the general population TTV loads were negatively associated with CD4+ cell counts, with an increased predisposition for an inverted CD4/CD8 ratio for individuals with TTV loads ≥4log copies/ml, thus promoting an immune risk phenotype.

    更新日期:2019-12-20
  • Predictors of functional decline in nursing home residents: the Shelter project
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-20
    Fedecostante M, Onder G, Eusebi P, et al.

    BackgroundThe aim of our study was to identify independent predictors of functional decline in older nursing home (NH) residents, taking into account both resident and facility characteristics. Methodslongitudinal observational study involving 1760 older (≥ 65 years) residents of NH participating in the SHELTER* study (57 NH in 8 countries). All residents underwent a comprehensive geriatric assessment using the interRAI LTCF. Functional decline was defined as an increase of at least one point in the MDS Long Form ADL scale during a one year follow-up. Facility and country effect were taken into account. ResultsDuring the study period 891 (50,6%) NH residents experienced ADL decline. Residents experiencing ADL decline were older, had lower disability at baseline, were more frequently affected by severe dementia and by urinary incontinence and used more antipsychotics. In the mixed effect logistic regression model factors independently associated with a higher risk of functional decline were dementia and urinary incontinence, whereas the presence of a geriatrician was a protective factor. ConclusionBoth resident and facility characteristics are associated with the risk of functional decline in NH residents. Increasing the quality of healthcare by involving a geriatrician in residents’ care might be an important strategy to improve the outcome of this vulnerable population.

    更新日期:2019-12-20
  • Patterns of Home Environmental Modification Use and Functional Health: The Women’s Health Initiative
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-14
    Welti L, Beavers K, Mampieri A, et al.

    BackgroundWe examined common patterns of home environmental modification (HEM) use and associated major (including disability-, cardiovascular-, and cancer-related) health conditions and events among older women. MethodsWomen, age 78.6±6.3 years (n=71,257), self-reported utilization of 9 types of HEMs (hand rails, grab bars, ramps, non-slip surfaces, tacking carpets/rugs, decreasing clutter, increasing lighting, raised sink/counter heights, other). Concurrent history of major health conditions and events was collected. Odds ratios (OR) were estimated based on overall HEM use and four latent classes [low HEM use (56%), rails/grab bars (20%), lighting/decluttering (18%), high HEM use (5%)], adjusted for age, marital status, race/ethnicity, education, depression, and obesity. Results55% of women reported using any HEM (overall), with strongest associations among disability-related conditions. ADL limitations were strongly associated with high HEM use (OR 8.16, 95% CI 6.62–10.05), railing/grab bar use (OR 4.02, 95% CI 3.26–4.95), and lighting/declutter use (OR 1.87, 95% CI 1.40–2.50) versus low HEM use. Recent falls were positively associated with overall HEM use (OR 1.79, 95% CI 1.72, 1.87); high HEM use (OR 2.89, 95% CI 2.64–3.16), railings/grab bars use (OR 2.32, 95% CI 2.18–2.48), and lighting/declutter use (OR 1.93, 95% CI 1.79–2.08) were positively associated with recent falls. Modest associations were observed between HEM use and select (i.e., atrial fibrillation, heart valve disease, stroke) cardiovascular outcomes. ConclusionsAmong older women, disability-related conditions, including functional limitations and recent falls, were strongly associated with overall HEM use, high HEM use, and railings/grab bar use.

    更新日期:2019-12-17
  • Everyday Discrimination and Kidney Function Among Older Adults: Evidence from the Health and Retirement Study
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-15
    Cobb R, Thorpe R, Jr, Norris K.

    BackgroundWith advancing age there is an increase in the time of and number of experiences with psychosocial stressors that may lead to the initiation and/or progression of chronic kidney disease (CKD). Our study tests whether one type of experience, everyday discrimination, predicts kidney function among middle and older adults. MethodsThe data were from 10,973 respondents (ages 52-100) in the 2006/2008 Health and Retirement Study, an ongoing biennial nationally representative survey of older adults in the United States. Estimated glomerular filtration rate (eGFR) derives from the Chronic Kidney Disease Epidemiology Collaboration equation. Our indicator of everyday discrimination is drawn from self-reports from respondents. Ordinary Least Squared regression (OLS) models with robust standard errors are applied to test hypotheses regarding the link between everyday discrimination and kidney function. ResultsEveryday discrimination was associated with poorer kidney function among respondents in our study. Respondents with higher everyday discrimination scores had lower eGFR after adjusting for demographic characteristics (B=-1.35, p<.05), and while attenuated, remained significant (B=-.79, p<.05) after further adjustments for clinical, health behavior, and socioeconomic covariates. ConclusionsOur study suggests everyday discrimination is independently associated with lower eGFR. These findings highlight the importance of psychosocial factors in predicting insufficiency in kidney function among middle-aged and older adults.

    更新日期:2019-12-17
  • The Prevalence of Orthostatic Hypotension: A Systematic Review and Meta-Analysis
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2018-08-29
    Saedon N, Pin Tan M, Frith J, et al.

    BackgroundOrthostatic hypotension (OH) is associated with increased risk of falls, cognitive impairment and death, as well as a reduced quality of life. Although it is presumed to be common in older people, estimates of its prevalence vary widely. This study aims to address this by pooling the results of epidemiological studies. MethodsMEDLINE, EMBASE, PubMed, Web of Science, and ProQuest were searched. Studies were included if participants were more than 60 years, were set within the community or within long-term care and diagnosis was based on a postural drop in systolic blood pressure (BP) ≥20 mmHg or diastolic BP ≥10 mmHg. Data were extracted independently by two reviewers. Random and quality effects models were used for pooled analysis. ResultsOf 23,090 identified records, 20 studies were included for community-dwelling older people (n = 24,967) and six were included for older people in long-term settings (n = 2,694). There was substantial variation in methods used to identify OH with differing supine rest duration, frequency and timing of standing BP, measurement device, use of standing and tilt-tables and interpretation of the diagnostic drop in BP. The pooled prevalence of OH in community-dwelling older people was 22.2% (95% CI = 17, 28) and 23.9% (95% CI = 18.2, 30.1) in long-term settings. There was significant heterogeneity in both pooled results (I2 > 90%). ConclusionsOH is very common, affecting one in five community-dwelling older people and almost one in four older people in long-term care. There is great variability in methods used to identify OH.

    更新日期:2019-12-13
  • Protein Intake and Functional Integrity in Aging: The Framingham Heart Study Offspring
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2018-09-24
    Hruby A, Sahni S, Bolster D, et al.

    BackgroundHigher protein intake is linked to maintenance of muscle mass and strength, but few studies have related protein to physical function and disability in aging. MethodsIn participants of the Framingham Heart Study Offspring, we examined associations between protein intake (g/d), estimated from food frequency questionnaires, and maintenance of functional integrity, as a functional integrity score based on responses to 17 questions from Katz Activities of Daily Living, Nagi, and Rosow-Breslau questionnaires, repeated up to five times (1991/1995–2011/2014) over 23 years of follow-up. Cox proportional hazard models were used to estimate risk of incident loss of functional integrity (functional integrity score ≤ 15th percentile). ResultsIn 2,917 participants (age 54.5 [9.8] years), baseline protein intake was 77.2 (15.6) g/d. The functional integrity score (baseline, mean 98.9, range 82.4–100.0) was associated with objective performance (gait speed, grip strength) and lower odds of falls, fractures, and frailty. Across follow-up, there were 731 incident cases of loss of functional integrity. In fully adjusted models, participants in the highest category of protein intake (median 92.2 g/d) had 30% lower risk of loss of functional integrity (hazard ratio [95% confidence interval] 0.70 [0.52, 0.95], p trend = .03), versus those with the lowest intake (median 64.4 g/d). However, sex-stratified analyses indicated the association was driven by the association in women alone (hazard ratio [95% confidence interval] 0.49 [0.32, 0.74], p trend = .002) and was nonsignificant in men (hazard ratio [95% confidence interval] 1.14 [0.70, 1.86], p trend = .59). ConclusionsHigher protein intake was beneficially associated with maintenance of physical function in middle-aged, high-functioning U.S. adults over the span of two decades. This association was particularly evident in women.

    更新日期:2019-12-13
  • Metabolic Effects of Breaking Prolonged Sitting With Standing or Light Walking in Older South Asians and White Europeans: A Randomized Acute Study
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2018-11-07
    Yates T, Edwardson C, Celis-Morales C, et al.

    BackgroundProlonged sitting is common in older adults and is associated with insulin resistance and poor cardiometabolic health. We investigate whether breaking prolonged sitting with regular short bouts of standing or light walking improves postprandial metabolism in older white European and South Asian adults and whether effects are modified by ethnic group. MethodsThirty South Asian (15 women) and 30 white European (14 women) older adults (aged 65–79 years) undertook three experimental conditions in random order. (a) Prolonged sitting: continuous sitting during an observation period if 7.5 hours consuming two standardized mixed meals. (b) Standing breaks: sitting interrupted with 5 minutes of standing every 30 minutes (accumulating 60 minutes of standing over the observation period). (c) Walking breaks: sitting interrupted with 5 minutes of self-paced light walking every 30 minutes (accumulating 60 minutes of walking). Blood samples (glucose, insulin, triglycerides) and blood pressure were sampled regularly throughout each condition. ResultsCompared with prolonged sitting, walking breaks lowered postprandial insulin by 16.3 mU/L, (95% CI: 19.7, 22.0) with greater reductions (p = .029) seen in South Asians (22.4 mU/L; 12.4, 32.4) than white Europeans (10.3 mU/L; 5.9, 14.7). Glucose (0.3 mmol/L; 0.1, 0.5) and blood pressure (4 mm Hg; 2, 6), but not triglycerides, were lower with walking breaks, with no ethnic differences. Standing breaks did not improve any outcome. ConclusionsBreaking prolonged sitting with short bouts of light walking, but not standing, resulted in clinically meaningful improvements in markers of metabolic health in older adults, with South Asians gaining a greater reduction in postprandial insulin. Trial RegistrationNCT02453204

    更新日期:2019-12-13
  • Geriatric Health Charts for Individual Assessment and Prediction of Care Needs: A Population-Based Prospective Study
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2018-12-04
    Santoni G, Calderón-Larrañaga A, Vetrano D, et al.

    BackgroundGeriatric health charts that are similar to pediatric growth charts could facilitate monitoring health changes and predicting care needs in older adults. We aimed to validate an existing composite score (Health Assessment Tool [HAT]) and provide provisional age-specific reference curves for the general older population. MethodsData came from the Swedish National study on Aging and Care in Kungsholmen (N = 3,363 participants aged 60 years and over examined clinically at baseline and 3 years later). HAT was validated by exploring its relationship with health indicators (logistic regression) and comparing its ability to predict care consumption with that of two of its components, morbidity and disability (receiver operating characteristic curve areas). A flowchart was developed to obtain individual-level HAT scores (nominal response method). Sex-specific health charts were derived by graphing seven percentile curves of age-related HAT change (logistic quantile regression). ResultsHAT scores above the age- and sex-specific median were related to good performance in chair-stand tests (odds ratio [OR] = 2.62, 95% confidence interval [CI]: 2.07–3.31), balance and grip tests (interaction balance grip test, OR = 1.15, 95% CI: 1.05–1.25), and good self-rated health (OR = 2.19, 95% CI: 1.77–2.71). Receiver operating characteristic curve areas (HAT vs number of chronic disorders) were formal care, 0.76 versus 0.58 (p value < .001); informal care, 0.74 versus 0.59 (p value < .001); hospital admission, 0.70 versus 0.66 (p value < .001); primary care visits, 0.71 versus 0.69 (p value > .05); and specialty care visits, 0.62 versus 0.65 (p value < .001). HAT consistently predicted medical and social care service use better than disability. ConclusionsHAT is a valid tool that predicts care consumption well and could be useful in developing geriatric health charts to better monitor health changes in older populations.

    更新日期:2019-12-13
  • Childhood Cognition and Age-Related Change in Standing Balance Performance From Mid to Later Life: Findings From a British Birth Cohort
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2018-12-08
    Blodgett J, Kuh D, Hardy R, et al.

    BackgroundCognitive processing plays a crucial role in the integration of sensory input and motor output that facilitates balance. However, whether balance ability in adulthood is influenced by cognitive pathways established in childhood is unclear, especially as no study has examined if these relationships change with age. We aimed to investigate associations between childhood cognition and age-related change in standing balance between mid and later life. MethodsData on 2,380 participants from the MRC National Survey of Health and Development were included in analyses. Repeated measures multilevel models estimated the association between childhood cognition, assessed at age 15, and log-transformed balance time, assessed at ages 53, 60–64, and 69 using the one-legged stand with eyes closed. Adjustments were made for sex, death, attrition, anthropometric measures, health conditions, health behaviors, education, other indicators of socioeconomic position (SEP), and adult verbal memory. ResultsIn a sex-adjusted model, 1 standard deviation increase in childhood cognition was associated with a 13% (95% confidence interval: 10, 16; p < .001) increase in balance time at age 53, and this association got smaller with age (cognition × age interaction: p < .001). Adjustments for education, adult verbal memory, and SEP largely explained these associations. ConclusionsHigher childhood cognition was associated with better balance performance in midlife, with diminishing associations with increasing age. The impact of adjustment for education, cognition and other indicators of SEP suggested a common pathway through which cognition is associated with balance across life. Further research is needed to understand underlying mechanisms, which may have important implications for falls risk and maintenance of physical capability.

    更新日期:2019-12-13
  • Moderation of the Association Between Chronic Medical Conditions and Functional Limitations Over Time by Physical Activity: Effects of Age
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-01-21
    Rector J, Marceau K, Friedman E, et al.

    BackgroundAge-related accumulation of chronic medical conditions increases disability in older adults. Physical activity potently combats chronic conditions and disability. However, it is unclear whether activity maintenance alleviates the effects of chronic conditions on disability and if this buffering effect differs with age. This study examined whether long-term physical activity can forestall functional limitations in the face of accumulating chronic conditions among middle-aged and older adults. MethodsParticipants (n = 2,119; 54.7% female) were from the Survey of Midlife Development in the United States. Self-reported physical activity, number of chronic conditions, and functional limitations were obtained across 18–20 years. Functional limitations were regressed against the change in chronic conditions, physical activity, and their interaction over time in a multilevel model of change. Baseline age was added as an additional moderator. ResultsFaster accumulation of chronic conditions [B(SE) = 2.08(0.32), p < .001] and steeper declines in activity [B(SE) = −2.29(0.41), p < .001] were associated with greater increases in functional limitations over time. Among those with faster-than-average increases in conditions, those who maintained activity had a slower progression of functional limitations, compared to those whose activity declined more rapidly [B(SE) = −11.18(3.96), p = .005]. Baseline age moderated the buffering effect of activity maintenance; older adults were protected against functional limitations only when conditions accumulated slowly [B(SE) = 0.23(0.08), p = .005]. ConclusionThis study provides evidence for an age-dependent buffering effect of activity maintenance on the longitudinal relationship between chronic conditions and functional limitations. Intervention strategies using physical activity to forestall disability should target midlife adults and consider the rate of condition accumulation.

    更新日期:2019-12-13
  • Living Longer, With or Without Disability? A Global and Longitudinal Perspective
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-01-09
    Lee J, Lau S, Meijer E, et al.

    BackgroundSignificant gains in life expectancy have been achieved, but living longer does not necessarily mean the years gained are productive and healthy. Different theories predict different patterns of time trends in old-age disability prevalence. MethodsUsing the Gateway to Global Aging Data, which provides internationally harmonized longitudinal data from the Health and Retirement Study and its sister surveys, we compare time trends (from 2004 to 2014) in disability prevalence across countries. ResultsDisability prevalence varies greatly across countries, and divergent time trends are observed across countries. For countries such as Belgium, Czechia, and Mexico, we observe an increase of disability prevalence, whereas in countries such as Denmark, England, Greece, Korea, Poland, and Sweden, we observe a substantial decrease in disability prevalence. Looking further into the severity of disability, we often observe differential trends in prevalence, but there is no evidence supporting the dynamic equilibrium hypothesis that predicts increased prevalence of modest disability but a decrease in severe disability prevalence. ConclusionsSignificant gains in life expectancy have translated into different gains in healthy years of life across different countries. Diverse time trends in disability prevalence across countries reaffirm that the expansion of late-life disability is not inevitable.

    更新日期:2019-12-13
  • Comparison of Mobility Indices for Predicting Early Death in Older Patients With Cancer: The Physical Frailty in Elderly Cancer Cohort Study
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-02-04
    Pamoukdjian F, Aparicio T, Zebachi S, et al.

    BackgroundTo assess and compare the ability of five mobility indices to predict 6-month mortality in older patients with cancer. MethodsAll consecutive ambulatory older patients with cancer referred for a geriatric assessment before a cancer treatment decision were included in a prospective two-center cohort study (Physical Frailty in Elderly Cancer) between 2013 and 2017. The mobility indices compared were the short physical performance battery, gait speed, hand grip strength, the one-leg stance balance test, and repeated falls. The primary endpoint was 6-month overall mortality. The adjusted hazard ratio (95% confidence interval [CI]) for each mobility index was estimated using a multivariate Cox proportional hazard model adjusted for sex, the Cumulative Illness Rating Scale for Geriatrics, the body mass index, cancer site/extension, and the provision of supportive care alone. The models’ predictive performances were assessed in terms of Harrell’s C index, net reclassification improvement, and the standardized net benefit. ResultsA total of 603 patients included (mean age: 81.2 ± 6.1 years; women: 54%; metastatic cancer: 45%). In multivariate analyses, an impairment in any of the mobility indices (with the exception of repeated falls) was independently associated with 6-month mortality following a geriatric assessment; the adjusted hazard ratio [95% CI] ranged from 2.35 [1.34–4.13] for the one-leg stance balance (C index: 0.74) to 3.03 [1.93–4.76] for the short physical performance battery (C index: 0.77). For each mobility index, inclusion in the multivariate model improved significantly the latter’s prediction of 6-month mortality. ConclusionsAmong mobility tests, short physical performance battery had the best discriminative value for predicting 6-month mortality in older patients with cancer.

    更新日期:2019-12-13
  • A Regression Tree for Identifying Risk Factors for Fear of Falling: The International Mobility in Aging Study (IMIAS)
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-02-08
    Curcio C, Wu Y, Vafaei A, et al.

    BackgroundWe determine the best combination of factors for predicting the risk of developing fear of falling (FOF) in older people via Classification Regression Tree (CaRT) analysis. MethodsCommunity-dwelling older adults living in Canada, Albania, Brazil, and Colombia were from International Mobility in Aging Study (IMIAS). In 2014, 1,725 participants (aged 65–74) were assessed. With a retention rate of 81%, in 2016, 1,409 individuals were reassessed. Risk factors for FOF were entered into the CaRT: age, sex, education, self-rated health, comorbidity, medication, visual impairment, frailty, cognitive deficit, depression, fall history, Short Physical Performance Battery (SPPB), walking aid use, and mobility disability measured by the Nagi questionnaire. ResultsThe classification tree included 12 end groups representing differential risks of FOF with a minimum of two and a maximum of five predictors. The first split in the tree involved impaired physical function (SPPB scores). Respondents with less than 8 in SPPB score and mobility disability had 82% risk of developing FOF at the end of 2-year follow-up. Between 23.2% and 82.3% of the risk of developing FOF in 2 years of follow-up were explained by only five variables: age, sex, self-rated health, functional impairment measured by SPPB, and mobility disability. In those with no functional impairment or mobility disability, levels of education, sex, and self-rated health were important predictors of FOF in the future. ConclusionThis classification tree included different groups based on specific combinations of a maximum of five easily measurable predictors with emphasis on impaired physical functioning risk factors for developing FOF.

    更新日期:2019-12-13
  • Trends in Risk of Limitations in Instrumental Activities of Daily Living Over Age in Older Persons With and Without Multiple Chronic Conditions
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-02-17
    Mueller-Schotte S, Zuithoff N, Van der Schouw Y, et al.

    BackgroundTo investigate trends over age by comorbidity status for the risk of limitations in individual activities of daily living for community-living older persons. MethodsA longitudinal population-based study was conducted in 9,319 community-living Dutch persons aged 60 years and older. Self-reported multiple chronic conditions (MCC) and nine instrumental activities of daily livings (IADLs) were assessed in 15 studies of the Dutch National Care for the Elderly Program (TOPICS-MDS). Risks of limitations in IADLs, odds ratios (per 5 years), and rate ratios (per 5 years) were calculated with mixed logistic and negative binomial regression models with age as the underlying timescale, stratified by number of MCC (no, 1–2, ≥ 3 MCC), and corrected for confounders. ResultsAt inclusion, the number of IADL limitations was highest for the “≥3 MCC” group (2.00 interquartile range [1.00–4.00]) and equal for “no MCC” or “1–2 MCC” (1.00 interquartile range [0.00–2.00]). Trends of individual IADLs depicted a higher risk in IADL limitation with increasing age over 2 years of follow-up, except for handling finances for the “no MCC” group. The longitudinal age effect on IADL limitations varied subject to MCC, being strongest for the “no MCC” group for most IADLs; grooming and telephone use were almost unaltered by age and MCC. ConclusionWe observed a decline in IADL functioning with increasing age over 2 years of follow-up in persons with and without MCC. The impact of MCC on IADL decline varied per IADL activity.

    更新日期:2019-12-13
  • Mechanistic target of rapamycin signaling in mouse models of accelerated aging
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-03-01
    Lee J, Kennedy B, Liao C, et al.

    The mechanistic target of rapamycin (mTOR) is an essential nutrient-sensing kinase that integrates and regulates a number of fundamental cellular processes required for cell growth, cell motility, translation, metabolism, and autophagy. mTOR signaling has been implicated in the progression of many human diseases, and its dysregulation has been reported in several pathological processes, especially in age-related human diseases and mouse models of accelerated aging. In addition, many studies have demonstrated that the regulation of mTOR activity has a beneficial effect on longevity in several mouse models of aging. However, not all mouse models of accelerated aging show positive effects on aging-associated phenotypes in response to targeting mTOR signaling. Here, we review the effects of interventions that modulate mTOR signaling on aging-related phenotypes in different mouse models of accelerated aging and discuss their implications with respect to aging and aging-related disorders.

    更新日期:2019-12-13
  • Next Generation Strategies for Geroprotection via mTORC1 Inhibition
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-02-22
    Dumas S, Lamming D, Salmon A.

    Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) with the pharmaceutical rapamycin prolongs the lifespan and healthspan of model organisms including rodents, with evidence now emerging that rapamycin and its analogs may also have rejuvenative effects in dogs and humans. However, the side effects associated with long-term rapamycin treatment, many of which are due to inhibition of a second mTOR complex, mTORC2, have seemed to preclude the routine use of rapamycin as a therapy for age-related diseases. Here, we discuss recent findings suggesting that strong, chronic inhibition of both mTOR complexes may not be necessary to realize the geroprotective effects of rapamycin. Instead, modestly but specifically inhibiting mTORC1 via a variety of emerging techniques, including intermittent or transient treatment with rapamycin derivatives, or specific dietary regimens, may be sufficient to promote health and longevity with reduced side effects. We will also discuss prospects for the development of new molecules that, by harnessing the detailed molecular understanding of mTORC1 signaling developed over the last decade, will provide new routes to the selective inhibition of mTORC1. We conclude that therapies based on the selective inhibition of mTORC1 may soon permit the safer treatment of diseases of aging.

    更新日期:2019-12-13
  • Organizational Innovation for Developing New Medicines That Target Aging and Age-Related Conditions
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-03-06
    Ford G, Lord J, Ferguson M, et al.

    The imperative to develop pharmacological strategies that increase healthspan, reduce years spent with disability, and prevent and treat age-related diseases and conditions is well recognized (1). The current approach to drug development is to target individual diseases and undertake clinical trials in participants without significant comorbidities or disabilities. Most patients who receive drug therapies in real life tend to be older people with multimorbidity, frailty, and polypharmacy and thus are not well served by this drug discovery model. Even in those older people with a single phenotypic disease, the situation is complicated by the fact that their disease will often have a multifactorial pathogenesis underpinned by the biological drivers of aging. The importance of including real life older people in clinical trials of drugs that target single diseases is well recognized, but the need to shift the drug discovery approach towards addressing the unique problems of older people such as multimorbidity, frailty, and sarcopenia is less well recognised (2). Moreover, there is a growing appreciation that it may be possible to treat the underlying biological process of aging, thereby influencing the onset of a suite of age-related conditions and diseases with a single intervention (3). The aging process and the complex needs of the older population create both an opportunity and a challenge to develop innovative approaches to drug discovery and clinical trials.

    更新日期:2019-12-13
  • Is Rapamycin a Dietary Restriction Mimetic?
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-03-11
    Unnikrishnan A, Kurup K, Salmon A, et al.

    Since the initial suggestion that rapamycin, an inhibitor of target of rapamycin (TOR) nutrient signaling, increased lifespan comparable to dietary restriction, investigators have viewed rapamycin as a potential dietary restriction mimetic. Both dietary restriction and rapamycin increase lifespan across a wide range of evolutionarily diverse species (including yeast, Caenorhabditis elegans, Drosophila, and mice) as well as reducing pathology and improving physiological functions that decline with age in mice. The purpose of this article is to review the research comparing the effect of dietary restriction and rapamycin in mice. The current data show that dietary restriction and rapamycin have different effects on many pathways and molecular processes. In addition, these interventions affect the lifespan of many genetically manipulated mouse models differently. In other words, while dietary restriction and rapamycin may have similar effects on some pathways and processes; overall, they affect many pathways/processes quite differently. Therefore, rapamycin is likely not a true dietary restriction mimetic. Rather dietary restriction and rapamycin appear to be increasing lifespan and retarding aging largely through different mechanisms/pathways, suggesting that a combination of dietary restriction and rapamycin will have a greater effect on lifespan than either manipulation alone.

    更新日期:2019-12-13
  • Brain Protein Synthesis Rates in the UM-HET3 Mouse Following Treatment With Rapamycin or Rapamycin With Metformin
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-03-13
    Reid J, Linden M, Peelor F, III, et al.

    Treatment with the mechanistic target of rapamycin (mTOR) inhibitor, rapamycin (RAP), alone and in combination with the antidiabetic drug, metformin (RAP+MET), extends lifespan in mice. The mechanisms underlying lifespan extension are unclear. One possibility is improved capacity for proteostatic maintenance. We have previously characterized peripheral protein synthesis rates following treatment with RAP. However, it is unknown if RAP+MET elicits similar changes, or if either treatment affects protein synthesis in the brain. We hypothesized that 8 weeks of treatment with RAP and RAP+MET would alter brain protein synthesis rates to reflect proteostatic processes. Using the stable isotopic tracer, deuterium oxide (D2O), we demonstrate in UM-HET3 mice that protein synthesis rates measured in whole brain were unaffected by treatment in young male mice, whereas RAP+MET decreased mitochondrial protein synthesis in young females. Conversely, RAP increased mitochondrial protein synthesis rates in older females. Activity through the AMPK/mTOR pathway was affected in a sex-specific manner in young mice, and minimal changes were observed in the older cohort. Thus, we establish D2O for measurements of biogenesis in the brain. These results provide initial insights into the effects of RAP and RAP+MET on brain protein synthesis. Additionally, these data emphasize that responses to slowed aging treatments vary with sex and age.

    更新日期:2019-12-13
  • Elevated Plasma Growth and Differentiation Factor 15 Is Associated With Slower Gait Speed and Lower Physical Performance in Healthy Community-Dwelling Adults
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-03-15
    Semba R, Gonzalez-Freire M, Tanaka T, et al.

    BackgroundGrowth and differentiation factor 15 (GDF-15) has been associated with obesity, muscle wasting, and cachexia. The receptor for GDF-15 was recently identified in the brainstem and regulates food intake and metabolism. The relationship of plasma GDF-15 with the age-associated decline of muscle mass and strength, gait speed, and physical performance in adults has not been well characterized. MethodsPlasma GDF-15, grip strength, 6-m gait speed, 400-m walking test time, lower extremity physical performance score, appendicular lean mass, and fat mass were measured in 194 healthy adult participants, aged 22–93 years, of the Baltimore Longitudinal Study of Aging. ResultsPlasma GDF-15 concentrations increased with age (p < .001) and were higher in whites compared with blacks and Asians (p = .04). Adults with higher plasma GDF-15 had slower 6-m gait speed, longer 400-m walking time, and lower physical performance score in multivariable analyses adjusting for age and race. Plasma GDF-15 was not associated with grip strength, appendicular lean mass, or fat mass. ConclusionsElevated plasma GDF-15 is associated with slower gait speed, higher 400-m walking time, and lower physical performance in very healthy community-dwelling adults. The relationship between plasma GDF-15 and sarcopenia-related outcomes may be stronger in the population not selected to be healthy, and this hypothesis should be tested in a representative population.

    更新日期:2019-12-13
  • The Association Between Self-Reported and Performance-Based Physical Function With Activities of Daily Living Disability in the Canadian Longitudinal Study on Aging
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-05-13
    Mayhew A, Griffith L, Gilsing A, et al.

    BackgroundPhysical function limitations precede disability and are a target to prevent or delay disability in aging adults. The objective of this article was to assess the relationship between self-report and performance-based measures of physical function with disability. MethodsBaseline data (2012–2015) from the Canadian Longitudinal Study on Aging (n = 51,338) was used. Disability was defined as having a limitation for at least one of 14 activities of daily living. Physical function was measured using 14 questions across three domains (upper body, lower body, and dexterity) and five performance-based tests (gait speed, timed up and go, single leg stance, chair rise, and grip strength). Logistic regression was used to assess the relationship between physical function operationalized as (i) at least one limitation, (ii) presence or absence of limitations in each individual domain/test, and (iii) number of domains/tests with limitations, with disability. ResultsIn the 21,241 participants with self-reported function data, the odds of disability were 1.87 (95% CI: 1.56–2.24), 6.78 (5.68–8.08), and 14.43 (11.50–18.1) for one, two, and three limited domains, respectively. In the 30,097 participants with performance-based measures of function, the odds of disability ranged from 1.53 (1.33–1.76) for one test limited to 14.91 (11.56–19.26) for all five tests limited. ConclusionsBoth performance-based and self-report measures of physical function were associated with disability. Each domain and performance test remained associated with disability after adjustment for the other domains and tests. Disability risk was higher when the number of self-report domains and performance-based limitations increased.

    更新日期:2019-12-13
  • Branched-Chain Amino Acids Have Equivalent Effects to Other Essential Amino Acids on Lifespan and Aging-Related Traits in Drosophila
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-03-20
    Juricic P, Grönke S, Partridge L, et al.

    Branched-chain amino acids (BCAAs) have been suggested to be particularly potent activators of Target of Rapamycin (TOR) signaling. Moreover, increased circulating BCAAs are associated with higher risk of insulin resistance and diabetes in both mice and humans, and with increased mortality in mice. However, it remains unknown if BCAAs play a more prominent role in longevity than do other essential amino acids (EAAs). To test for a more prominent role of BCAAs in lifespan and related traits in Drosophila, we restricted either BCAAs or a control group of three other EAAs, threonine, histidine and lysine (THK). BCAA restriction induced compensatory feeding, lipid accumulation, stress resistance and amelioration of age-related gut pathology. It also extended lifespan in a dietary-nitrogen-dependent manner. Importantly, the control restriction of THK had similar effects on these phenotypes. Our control diet was designed to have every EAA equally limiting for growth and reproduction, and our findings therefore suggest that the level of the most limiting EAAs in the diet, rather than the specific EAAs that are limiting, determines the response of these phenotypes to EAA restriction.

    更新日期:2019-12-13
  • Rationale and Study Design of a Randomized Clinical Trial of Metformin to Prevent Frailty in Older Adults With Prediabetes
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-03-19
    Espinoza S, Musi N, Wang C, et al.

    BackgroundFrailty is a geriatric syndrome that leads to poor health outcomes with aging. Previous studies have demonstrated that insulin resistance and inflammation predict frailty onset. Metformin is a widely used, well-tolerated drug that improves insulin sensitivity and displays anti-inflammatory properties. It is also known to prevent diabetes onset in adults with prediabetes. We hypothesize that metformin in older adults with prediabetes will promote healthy aging and prevent frailty. Here we describe an ongoing placebo-controlled, double-blinded clinical trial of metformin for the prevention of frailty in older adults with prediabetes. MethodsOlder adults aged more than 65 years are randomized to metformin or placebo and are followed for 2 years. Prediabetes, required for inclusion, is assessed by 2-hour oral glucose tolerance test. Exclusion criteria are baseline frailty (Fried criteria), diabetes, dementia, untreated depression, active malignancy, or severe cardiovascular, pulmonary, and neurologic diseases. Primary outcome is frailty; secondary outcomes are physical function (Short Physical Performance Battery), systemic and skeletal muscle tissue inflammation, muscle insulin signaling, insulin sensitivity (insulin clamp), glucose tolerance (oral glucose tolerance test), and body composition (dual-energy x-ray absorptiometry). Subjects are followed every 3 months for safety assessments and every 6 months for frailty assessment (Fried criteria) and oral glucose tolerance test, and every 12 or 24 months for secondary outcomes. Enrollment of 120 subjects (completers) will take place over a 2-year period. ConclusionMetformin is being examined in this study as a potential therapeutic agent to prevent frailty in older adults with prediabetes. Findings from this trial may have future implications for the screening and potential treatment of prediabetes in older patients with metformin for the prevention of frailty.

    更新日期:2019-12-13
  • Differential Effects of Rapamycin and Metformin in Combination With Rapamycin on Mechanisms of Proteostasis in Cultured Skeletal Myotubes
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-03-31
    Wolff C, Reid J, Musci R, et al.

    mTOR inhibition extends life span in multiple organisms. In mice, when metformin treatment (Met) is added to the mTOR inhibitor rapamycin (Rap), median and maximal life span is extended to a greater degree than with Rap or Met alone. Treatments that extend life span often maintain proteostasis. However, it is less clear how individual tissues, such as skeletal muscle, maintain proteostasis with life span–extending treatments. In C2C12 myotubes, we used deuterium oxide (D2O) to directly measure two primary determinants of proteostasis, protein synthesis, and degradation rates, with Rap or Met+Rap treatments. We accounted for the independent effects of cell growth and loss, and isolated the contribution of autophagy and mitochondrial fission to obtain a comprehensive assessment of protein turnover. Compared with control, both Rap and Met+Rap treatments lowered mitochondrial protein synthesis rates (p < .001) and slowed cellular proliferation (p < .01). These changes resulted in greater activation of mechanisms promoting proteostasis for Rap, but not Met+Rap. Compared with control, both Rap and Met+Rap slowed protein breakdown. Autophagy and mitochondrial fission differentially influenced the proteostatic effects of Rap and Met+Rap in C2C12 myotubes. In conclusion, we demonstrate that Met+Rap did not increase protein turnover and that these treatments do not seem to promote proteostasis through increased autophagy.

    更新日期:2019-12-13
  • Rapamycin Affects Palmitate-Induced Lipotoxicity in Osteoblasts by Modulating Apoptosis and Autophagy
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-06-18
    Al Saedi A, A. Goodman C, E. Myers D, et al.

    Bone marrow fat infiltration is one of the hallmarks of aging and osteoporotic bones. Marrow adipocytes produce substantial amounts of palmitic acid (PA). PA is toxic to bone-forming osteoblasts in vitro, affecting their differentiation, function, and survival. Since rapamycin (RAP)-induced inhibition of target of rapamycin complex 1 (mTORC1) activates autophagy and prevents apoptosis, we hypothesized that RAP may preserve osteoblast viability and reduce PA-induced lipotoxicity. Normal human osteoblasts were incubated with RAP in the presence of a lipotoxic concentration of PA or vehicle for 24 and 48 hours. Expression of LC3 protein levels and the phosphorylation of the direct mTORC1 target p70S6K1-T389 were quantified by Western blot. Lysosomes and autophagosomes were studied using confocal fluorescence imaging, lysotracker, and live-cell imaging. RAP reduced PA-induced apoptosis. In addition, PA-induced autophagosome formation increased substantially over the time-course, an effect that was significantly regulated by the presence of RAP in the media. In addition, LC3I/II ratios were higher in PA-induced cells with RAP whereas p70S6K1-T389 were lower in PA and RAP together. In summary, this study highlights the role of the RAP-sensitive mTORC1 pathway in normal human osteoblasts under lipotoxic conditions. RAP-associated therapies could, potentially, be targeted for specific roles in osteoporosis and aging bone.

    更新日期:2019-12-13
  • TORwards a Victory Over Aging
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-09-23
    Lamming D, Salmon A.

    For over two thousand years, tales of a so-called “Fountain of Youth” have reflected the human desire to extend life span and health span. The discovery that calorie restriction (CR) can extend the life span of rodents and even non-human primates has excited the imagination and provided valuable insights into the aging process, yet is of limited clinical use due to the inability of most people to adhere to such an abstemious diet. A decade ago, the National Institute on Aging Interventions Testing Program identified rapamycin, an inhibitor of the protein kinase mTOR (mechanistic Target Of Rapamycin) purified from bacteria discovered on Easter Island in the 1970s, as capable of extending the life span of mice (1). While not the proverbial fountain of youth, the ability of rapamycin to extend life span when treatment was started in middle age was a clear demonstration that developing pharmaceuticals to extend human life span might truly be possible. Since then, numerous studies from multiple labs have demonstrated that rapamycin can extend the life span of mice, even if given transiently or intermittently, with short-term rapamycin treatment also protecting or rejuvenating rodent tissues (2). In this special issue, we have collected a series of primary papers and reviews at the cutting edge of research into understanding the potent biological effects of rapamycin and how these can be translated into effective therapeutic options for age-related disease.

    更新日期:2019-12-13
  • James Edgar Paullin: Pioneer in Geriatrics and Gerontology
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-10-05
    Newman A.

    In this issue of the Journal of Gerontology: Medical Sciences, we celebrate the 75th anniversary of the Gerontological Society of America with reflections on articles from 1946, the inaugural year of the journal. The field of medical gerontology or geriatrics has its roots in the British National Health Service in the 1930s (1) and was first established in the United States in the 1940s. In spite of the needs engendered by the aging of the population, controversies continue today as to the role of the discipline in modern medicine. In reviewing the issue, I was struck by a number of articles that discussed the need for geriatrics and gerontology in much the same way as today, including the article: “The Relationship of Medical Practice to Gerontology” by James E. Paullin (2).

    更新日期:2019-12-13
  • Corrigendum to: Next Generation Strategies for Geroprotection via mTORC1 Inhibition
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-09-30
    Dumas S, Lamming D.

    In the article “Next generation strategies for geroprotection via mTORC1 inhibition,” the citation provided for the 9th reference was incorrect. Reference 9 should cite:

    更新日期:2019-12-13
  • Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-07-29
    Mau T, O’Brien M, Ghosh A, et al.

    The National Institute on Aging (NIA)-sponsored Interventions Testing Program (ITP) has identified a number of dietary drug interventions that significantly extend life span, including rapamycin, acarbose, and 17-α estradiol. However, these drugs have diverse downstream targets, and their effects on age-associated organ-specific changes are unclear (Nadon NL, Strong R, Miller RA, Harrison DE. NIA Interventions Testing Program: investigating putative aging intervention agents in a genetically heterogeneous mouse model. EBioMedicine. 2017;21:3–4. doi:10.1016/j.ebiom.2016.11.038). Potential mechanisms by which these drugs extend life could be through their effect on inflammatory processes often noted in tissues of aging mice and humans. Our study focuses on the effects of three drugs in the ITP on inflammation in gonadal white adipose tissue (gWAT) of HET3 mice—including adiposity, adipose tissue macrophage (ATM) M1/M2 polarization, markers of cellular senescence, and endoplasmic reticulum stress. We found that rapamycin led to a 56% increase of CD45+ leukocytes in gWAT, where the majority of these are ATMs. Interestingly, rapamycin led to a 217% and 106% increase of M1 (CD45+CD64+CD206−) ATMs in females and males, respectively. Our data suggest rapamycin may achieve life-span extension in part through adipose tissue inflammation. Additionally, HET3 mice exhibit a spectrum of age-associated changes in the gWAT, but acarbose and 17-α estradiol do not strongly alter these phenotypes—suggesting that acarbose and 17- α estradiol may not influence life span through mechanisms involving adipose tissue inflammation.

    更新日期:2019-12-13
  • Differential Effects of Rapamycin on Glucose Metabolism in Nine Inbred Strains
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-07-04
    Reifsnyder P, Te A, Harrison D, et al.

    Studies in mice suggest that rapamycin has a negative impact on glucose homeostasis by inducing insulin resistance. However, results have been inconsistent and difficult to assess because the strains, methods of treatment, and analysis vary among studies. Using a consistent protocol, we surveyed nine inbred strains of mice for the effect of rapamycin on various aspects of glucose metabolism. Across all strains, rapamycin significantly delayed glucose clearance after challenge. However, rapamycin showed no main effect on systemic insulin sensitivity. Analysis of individual strains shows that rapamycin induced higher glucose values at 15 minutes post-challenge in 7/9 strains. However, only three strains show rapamycin-induced reduction in glucose clearance from 15 to 120 minutes. Although pancreatic insulin content was reduced by rapamycin in seven strains, none showed reduced serum insulin values. Although one strain showed no effects of rapamycin on glucose metabolism (129), another showed increased systemic insulin sensitivity (B6). We suggest that rapamycin likely inhibits insulin production and secretion in most strains while having strain-specific effects on glucose clearance without altering systemic insulin sensitivity. This strain survey indicates that genetic differences greatly influence the metabolic response to rapamycin.

    更新日期:2019-12-13
  • Testing the Geroscience Hypothesis: Early Days
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-13
    Kritchevsky S, Justice J.

    In this issue, Espinoza and colleagues present the design of a 2-year randomized, double-blind, controlled, clinical trial testing whether 2,000 mg/day of metformin retards the advancement of frailty in prediabetic older adults. Demonstrating that any drug can deflect the progression of frailty would be a major milestone in geriatrics, but this study is also important within the larger frame of geroscience which hypothesizes that human health can be improved by directly targeting the biology of aging (1). Support for this hypothesis is found in studies of model organisms, which show that targeting these pathways in a variety of ways—including the administration of metformin—can increase health span and lifespan (2). The study by Espinoza is one of the few rigorously designed trials to test a drug in a context that has direct implications for evaluating the geroscience hypothesis.

    更新日期:2019-12-13
  • Accelerating the Search for Interventions Aimed at Expanding the Health Span in Humans: The Role of Epidemiology
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-11-13
    Newman A, Kritchevsky S, Guralnik J, et al.

    BackgroundExtensive work in basic and clinical science suggests that biological mechanisms of aging are causally related to the development of disease and disability in late life. Modulation of the biological mechanisms of aging can extend both life span and health span in animal models, but translation to humans has been slow. MethodsSummary of workshop proceedings from the 2018–2019 Epidemiology of Aging Workshop hosted by the Intramural Research Program at the National Institute on Aging. ResultsEpidemiologic studies play a vital role to progress in this field, particularly in evaluating new risk factors and measures of biologic aging that may influence health span, as well as developing relevant outcome measures that are robust and relevant for older individuals. ConclusionsAppropriately designed epidemiological studies are needed to identify targets for intervention and to inform study design and sample size estimates for future clinical trials designed to promote health span.

    更新日期:2019-12-13
  • Longitudinal Association Between Perceived Fatigability and Cognitive Function in Older Adults: Results from the Baltimore Longitudinal Study of Aging
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-12
    Salerno E, Wanigatunga A, An Y, et al.

    BackgroundCognitive decline is consistently associated with diminished life satisfaction and inability to live independently. Identifying early, novel markers of cognitive decline is imperative for improving clinical detection and promoting long-term quality of life. Fatigability, one’s perceived exertion after a standardized walking task, has been associated with declines in physical function; however, it remains unclear as to whether these effects may also extend to cognitive function. MethodsWe examined whether perceived fatigability, assessed as the rating of perceived exertion (RPE) after a 5-minute slow-paced treadmill walk (0.67 m/s, 0% grade), is longitudinally associated with cognitive performance in the domains of memory, executive functions, language, and attention among 934 cognitively intact individuals aged > 50 years participating in the Baltimore Longitudinal Study of Aging (BLSA) (Mage=69.6±10.1, 51.9% female). Continuous associations between RPE and each domain (individual test and composite scores) were assessed using linear mixed effect models adjusted for demographics and comorbid conditions. ResultsIn fully adjusted models, higher fatigability at baseline was associated with declines in all cognitive domains over an average 2.2 years of follow up (p<0.04 for all). Longitudinally, increased fatigability over time was associated with worsened executive functions (β=-0.01, p=0.002). DiscussionThese findings suggest that perceived fatigability after a standardized walking task may aid in identification of individuals at a higher risk of future cognitive decline. Future research should examine underlying biological mechanisms contributing to this relationship as well as whether future interventions may target fatigability in mid-life to attenuate age-related cognitive decline.

    更新日期:2019-12-13
  • The Roles of Body Composition and Specific Strength in the Relationship Between Race and Physical Performance in Older Adults
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-11
    Chiles Shaffer N, Simonsick E, Thorpe R, Jr, et al.

    BackgroundSocioeconomics may explain black–white differences in physical performance; few studies examine racial differences among socioeconomically similar groups. Performance is also affected by body composition and specific strength, which differ by race. We assessed whether racial differences in physical performance exist among older adults with high education and similar income and whether body composition and specific strength attenuate observed differences. MethodsCross-sectional analysis of 536 men (18% black) and 576 women (28% black) aged more than 60 years from the Baltimore Longitudinal Study of Aging. Body composition was evaluated using dual-energy x-ray absorptiometry. Specific strength was assessed by quadricep peak torque divided by height-normalized thigh cross-sectional area and grip strength divided by body mass index-normalized appendicular lean mass. Physical performance was assessed using usual gait speed and fast 400 m walk time. Sex-stratified linear regression models, adjusted for age, height, education, and recent income, determined whether body composition or specific strength attenuated associations between race and physical performance. ResultsBlacks were younger, with higher weight and appendicular lean mass. Black women had higher percent fat and specific strength. In both sexes, blacks had poorer physical performance after adjustment for socioeconomic factors. In women, neither body composition nor specific strength altered the association with gait speed. In men, neither body composition nor specific strength attenuated racial differences in either performance measure. ConclusionsPoorer physical performance among black compared to white older adults persists among persons with high education and similar income and cannot generally be attributed to differences in body composition or specific strength.

    更新日期:2019-12-11
  • Orthostatic hypotension and novel blood pressure associated gene variants in older adults: data from the TILDA Study
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-10
    Laird E, O’Halloran A, Fedorowski A, et al.

    Orthostatic hypotension (OH) is associated with increased risk of trauma and cardiovascular events. Recent studies have identified new genetic variants that influence orthostatic blood pressure (BP). The aim of this study was to investigate the associations of candidate gene loci with orthostatic BP responses in older adults. A total of 3,430 participants aged ≥50 years from The Irish Longitudinal Study on Ageing (TILDA) with BP measures and genetic data from twelve single-nucleotide polymorphism (SNP) linked to BP responses were analysed. Orthostatic BP responses were recorded at each 10 second interval and were defined as OH (SBP drop ≥20mmHg or DBP drop ≥10mmHg) at the time-points 40, 90 and 110 seconds. We defined sustained OH (SOH) as a drop that exceeded consensus BP thresholds for OH at 40, 90 and 110 seconds after standing. Logistic regression analyses modelled associations between the candidate SNP alleles and OH. We report no significant associations between OH and measured SNPs after correction for multiple comparisons apart from the SNP rs5068 where proportions of the minor allele was significantly different between cases and controls for SOH 40 (p=0.002). After adjustment for covariates in a logistic regression, those with the minor G allele (compared to the A allele) had a decreased incidence rate ratio (IRR) for SOH 40 (IRR 0.45, p=0.001, 95% CI 0.29-0.72). Only one SNP linked with increased natriuretic peptide concentrations was associated with OH. These results suggest that genetic variants may have a weak impact on OH but needs verification in other population studies.

    更新日期:2019-12-11
  • Sharp rise in fall-induced cervical spine injuries among older adults between 1970 and 2017
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-07
    Kannus P, Niemi S, Parkkari J, et al.

    BackgroundFall-induced injuries in older adults are a major public health challenge. MethodsWe determined the current trends in the number and age-adjusted incidence of fall-induced severe cervical spine injuries among older adults in Finland by taking into account all spersons 50 years of age or older who were admitted to Finnish hospitals for primary treatment of these injuries between 1970 and 2017. Similar patients aged 20-49 years served as a reference group. ResultsThe annual number of fall-induced severe cervical spine injuries among older Finnish adults rose steeply during the follow-up, from 59 in 1970 to 502 in 2017. The age-adjusted incidence of injury (per 100,000 persons) was higher in men than women throughout this period and showed a clear increase from 1970 to 2017: from 8.4 to 25.0 in men, and from 2.8 to 13.9 in women. In both sexes, the increase was most prominent in the oldest age group, persons aged 80 years or older. In the reference group, the injury incidence declined by time. ConclusionsThe number and incidence of fall-induced severe cervical spine injuries among older Finns showed a sharp rise between 1970 and 2017. An increase in the average risk of serious falls may partly explain the phenomenon. Effective fall and injury prevention measures are urgently needed since further aging of the population is likely to aggravate the problem in the near future.

    更新日期:2019-12-09
  • Yoga, Health-Related Quality of Life and Mental Well-Being: A Re-analysis of a Meta-analysis using the Quality Effects Model
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-09
    Kelley G, Kelley K.

    BACKGROUNDProvide robust and practically relevant information regarding the association between yoga, health-related quality-of-life (HRQOL) and mental well-being (MWB) in older adults. METHODSData were derived from a recent meta-analysis of 12 randomised controlled yoga trials representing 752 adults >60 years of age. Standardized mean difference effect sizes (ES’s) were pooled using the recently developed quality effects model and 95% compatibility intervals (CI). Small-study effects were examined using the Doi plot and Luis Furuya-Kanamori (LFK) index. Sensitivity and cumulative meta-analyses were conducted as well as percentile improvement, number needed to treat (NNT), and number to benefit. The GRADE instrument was used to assess the strength of the evidence. RESULTSYoga was associated with improvements in both HRQOL (ES = 0.51, 95% CI, 0.25-0.77, I2 =63.1%) and MWB (ES = 0.39, 95% CI, 0.15-0.63, I2 =56.2%). Percentile improvements were 19.5 for HRQOL and 15.3 for MWB while the NNT was 4 for HRQOL and 5 for MWB. An estimated 378,222 and 302,578 US yoga-practicing adults >65 years of age could potentially improve their HRQOL and MWB, respectively. Major asymmetry suggestive of small-study effects was observed for MWB but not HRQOL. Further examination for asymmetry revealed that greater improvements in MWB were associated with more (151 versus 68) minutes of yoga per week (p=0.007). Overall strength of evidence was considered “high” for HRQOL and “moderate” for MWB. CONCLUSIONSYoga is associated with improvements in HRQOL and MWB among older adults, with approximately 150 minutes or more per week possibly optimal.

    更新日期:2019-12-09
  • Non-cardiac-related morbidity, mobility limitation, and outcomes in older adults with heart failure
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-09
    Tisminetzky M, Gurwitz J, Fan D, et al.

    BackgroundTo examine the individual and combined associations of non-cardiac-related conditions and mobility limitation with morbidity and mortality in adults with heart failure (HF). MethodsWe conducted a retrospective cohort study in a large, diverse group of adults with HF from five U.S. integrated healthcare delivery systems. We characterized patients with respect to the presence of non-cardiac conditions (<3 vs ≥3) and/or mobility impairment (defined by the use/nonuse of a wheelchair, cane, or walker), categorizing them into four subgroups. Outcomes included all-cause death and hospitalizations for HF or any cause. ResultsAmong 114,553 adults diagnosed with HF (mean age: 73 years old, 46% women), compared with <3 non-cardiac conditions/no mobility limitation, adjusted hazard ratios (HR) for all-cause death among those with <3 non-cardiac conditions/mobility limitation, ≥3 non-cardiac conditions/no mobility limitation, ≥3 non-cardiac conditions/mobility limitation (vs.) were 1.40 (95% CI, 1.31-1.51), 1.72 (95% CI, 1.69-1.75), and 1.93 (95% CI, 1.85-2.01), respectively. We did not observe an increased risk of any-cause or HF-related hospitalization related to the presence of mobility limitation among those with a greater burden of non-cardiac multimorbidity. Consistent findings regarding mortality were observed within groups defined according to age, gender, and HF type (preserved, reduced, mid-range ejection fraction), with the most prominent impact of mobility limitation in those <65 years of age. ConclusionsThere is an additive association of mobility limitation, beyond the burden of non-cardiac multimorbidity, on mortality for patients with HF, and especially prominent in younger patients.

    更新日期:2019-12-09
  • Sex Differences in the Association Between Pentraxin 3 and Cognitive Decline: The Cardiovascular Health Study
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-06
    Miller L, Jenny N, Rawlings A, et al.

    BackgroundThe importance of systemic inflammation, measured by C-reactive protein, in cognitive decline has been demonstrated; however, the role of vascular inflammation is less understood. Pentraxin 3 (PTX3) is a novel marker of vascular inflammation. MethodsWe followed adults 65 and older, free of cardiovascular disease (CVD) for up to 9 years (n = 1,547) in the Cardiovascular Health Study. We evaluated the relationship between PTX3 and change in cognitive function, measured using the Modified Mini-Mental State Examination (3MSE), and incident cognitive impairment (3MSE < 80). Mediation by CVD events, and effect modification by sex and apolipoprotein E ɛ4 allele (APOE4) were also examined. ResultsThe average decline in 3MSE was 0.77 points per year. The association between PTX3 and change in 3MSE differed between women and men (p = .02). In the adjusted model, each standard deviation higher in PTX3 was associated with a 0.20 greater decline in 3MSE score per year in women over follow-up (95% CI: −0. 37, −0.03; p = .02), compared to no change in men (β = 0.07; 95% CI: −0.08, 0.22). CVD events had a minor effect on the associations. No effect modification by APOE4 was found, although we observed the association of PTX3 and cognitive impairment in women was attenuated and nonsignificant after adjustment for APOE4. There was a paradoxical protective association between PTX3 and reduced cognitive impairment in men, even after adjustment for APOE4. ConclusionsWe found that vascular inflammation was significantly associated with cognitive decline in older women, but not men.

    更新日期:2019-12-07
  • The Gut Microbiome as a Therapeutic Target for Cognitive Impairment
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-07
    Sun Y, Baptista L, Roberts L, et al.

    Declining cognitive functions in older individuals have enormous emotional, clinical and public health consequences. Thus therapeutics for preserving function and keeping older adults living independently are imperative. Aging is associated dysbiosis, defined as a loss of number and diversity in gut microbiota, which has been linked with various aspects of cognitive functions. Therefore, the gut microbiome has the potential to be an important therapeutic target for symptoms of cognitive impairment. In this review, we summarize the current literature regarding the potential for gut-targeted therapeutic strategies for prevention/treatment of the symptoms of cognitive impairment. Specifically, we discuss four primary therapeutic strategies: wild-type and genetically modified probiotics, fecal microbiota transplantation, physical exercise, and high-fiber diets and specifically link these therapies to reducing inflammation. These strategies may hold promise as treatment paradigms symptoms related to cognitive impairment.

    更新日期:2019-12-07
  • Unravelling the association between gait and mortality - one step at a time
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-06
    Dommershuijsen L, Isik B, Darweesh S, et al.

    BackgroundSlowness of walking is one of the very first signs of aging and is considered a marker for overall health that is strongly associated with mortality risk. In this study we sought to disentangle the clinical drivers of the association between gait and mortality. MethodsWe included 4,490 participants of the Rotterdam Study who underwent a gait assessment between 2009 and 2015 and were followed-up for mortality until 2018. Gait was assessed with an electronic walkway and summarized into the domains Rhythm, Phases, Variability, Pace, Tandem, Turning, and Base of Support. Cox models adjusted for age, sex, and height were built and consecutively adjusted for six categories of health indicators (lifestyle, musculoskeletal, cardiovascular, pulmonary, metabolic, and neurological). Analyses were repeated in comorbidity-free individuals. ResultsMultiple gait domains were associated with an increased risk of mortality, including Pace (HR per SD worse gait, adjusted for other domains: 1.34 [1.19-1.50]), Rhythm (HR: 1.12 [1.02-1.23]) and Phases (HR: 1.12 [1.03-1.21]). Similarly, a 0.1 m/s decrease in gait speed was associated with a 1.21 [1.15-1.27] times higher hazard of mortality (HR fully adjusted: 1.14 [1.08-1.20]). In a comorbidity-free subsample, the hazard ratio per 0.1 m/s decrease in gait speed was 1.25 [1.09-1.44]. Cause-specific mortality analyses revealed an association between gait speed and multiple causes of death. ConclusionsSeveral gait domains were associated with mortality risk, including Pace which primarily represents gait speed. The association between gait speed and mortality persisted after an extensive adjustment for covariates, suggesting that gait is a marker for overall health.

    更新日期:2019-12-06
  • The Unexplored World of Human Virome, Mycobiome, and Archaeome in Aging
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-12-05
    Barrera-Vázquez O, Gomez-Verjan J, Anderson R.

    In the last decades, improvements in different aspects of sanitation, medical care, and nutrition, among others, have permitted an increase in the average lifespan of human population around the world. These advances have stimulated an increased interest in the study of the aging process and age-sensitive characteristics, such as the microbial community that colonizes the human body (microbiome). The human microbiome is composed of bacteria (bacteriome), archaea (archaeome), fungi (mycobiome), and viruses (virome). To date, research has mainly been centered on the composition of the bacteriome, with other members remain poorly studied. Interestingly, changes in the composition of the microbiome have been implicated in aging and age-related diseases. Therefore, in the present perspective, we suggest expanding the scope to research to include the role and the possible associations that the other members of the microbiome could have in the aging organism. An expanded view of the microbiome would increase our knowledge of the physiology of aging and may be particularly valuable for the treatment and diagnosis of age-related diseases.

    更新日期:2019-12-05
  • Corrigendum to: The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-11-29
    Kuo C, Joaquim M, Kuchel G, et al.

    In the article, “The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects,” the first two sentences of the Funding section have been updated to the following:

    更新日期:2019-11-30
  • Age-Related Changes in Cognitive and Physical Performance
    J. Gerontol. A Biol. Sci. Med. Sci. (IF 4.711) Pub Date : 2019-11-27
    Rosano C.

    Dr. Boley’s considerations on peak of cognitive and physical performance across the lifespan (1) remain of high relevance for gerontologists today, 75 years after its initial publication on the Journal of Gerontological Medical Science.

    更新日期:2019-11-28
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