MicroRNAs (miRNAs) are potent regulators of multiple biological processes. Previous studies have demonstrated that miR-146a-5p increases in normal mice during aging, while long-living Ames dwarf (df/df) mice maintain youthful levels of this miRNA. The aim of this study was to elucidate the involvement of miR-146a-5p in modulating cellular senescence and apoptosis in visceral adipose tissue of df/df

To estimate dopaminergic dysfunction in patients with Parkinson disease (PD) during the premotor stage and to investigate the effect of genetic factors on the trajectories. Using longitudinal dopamine transporter single-photon emission computed tomography data from 367 sporadic PD (sPD), 72 LRRK2 (G2019S), and 39 GBA (N370S) PD patients in the Parkinson’s Progression Markers Initiative (PPMI) study

The beneficial effects of regular physical activity in promoting health and preventing chronic diseases are well documented. The relationship between regular physical activity and the risk of pneumonia is uncertain. We aimed to evaluate the magnitude and specificity of the prospective association between regular physical activity and the risk of pneumonia using a systematic review and meta-analysis

Accumulation of senescent cells may drive age-associated alterations and pathologies. Senolytics are promising therapeutics that can preferentially eliminate senescent cells. Here, we performed a high-throughput automatized screening (HTS) of the commercial LOPAC®Pfizer library on aphidicolin-induced senescent human fibroblasts, to identify novel senolytics. We discovered the nociceptin receptor FQ

Gait disturbance and imbalance are the major symptoms of Parkinson disease (PD), with fall being the most undesirable consequence. However, few effective evidence-based treatments are available for alleviating these symptoms and preventing falls. Cholinesterase inhibitors (ChEIs) are a well-established treatment for PD dementia with possible impacts on gait, balance, and fall reduction. The present

Background Cerebral small vessel disease (cSVD) is a late consequence of cerebral microvascular dysfunction (MVD). MVD is hard to measure in the brain due to its limited accessibility. Extracerebral MVD (eMVD) measures can give insights in the etiology of cerebral MVD, as MVD may be a systemic process. We aim to investigate whether a compound score consisting of several eMVD measures is associated

In the last decades, the scientific community spared no effort to elucidate the therapeutic potential of mesenchymal stromal cells (MSCs). Unfortunately, in vitro cellular senescence occurring along with a loss of proliferative capacity is a major drawback in view of future therapeutic applications of these cells in the field of regenerative medicine. Even though insight into the mechanisms of replicative

INTRODUCTION Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population, data on infants and adolescents with DS are missing. METHODS Neuronal-derived extracellular vesicles (nEVs) were

Protein-coding variants in the GBA gene modulate susceptibility and progression in ~10% of patients with Parkinson’s disease (PD). GBA encodes the β-glucocerebrosidase enzyme that hydrolyzes glucosylceramide. We hypothesized that GBA mutations will lead to glucosylceramide accumulation in cerebrospinal fluid (CSF). Glucosylceramide, ceramide, sphingomyelin, and lactosylceramide levels were measured

Parkinson’s disease (PD) is one of the most common neurodegenerative disease, and is so far not considered curable. PD patients suffer from several motor and non-motor symptoms, including gastrointestinal dysfunctions and alterations of the enteric nervous system. Constipation and additional intestinal affections can precede the classical motor symptoms by several years. Recently, we reported effects

The pathophysiology of Alzheimer's disease (AD) remains to be elucidated. The amyloid hypothesis holds explanatory power but has limitations. This article suggests that amyloid deposition and increased permeability of the blood-brain barrier are independent early events in the disease process, which together fashion a distinct microglial activation phenotype. Downstream events including, phagocytosis

INTRODUCTION Alzheimer's disease (AD) is associated with altered metabolites. This study aimed to determine the validity of using circulating metabolites to differentiate AD from other dementias. METHODS Blood metabolites were measured in three data sets. Data set 1 (controls, 27; AD, 28) was used for analyzing differential metabolites. Data set 2 (controls, 93; AD, 92) was used to establish a diagnostic

INTRODUCTION Motoric cognitive risk (MCR), a clinical syndrome characterized by slow gait speed and subjective cognitive complaints, has been associated with dementia risk. The neuropathological features underlying MCR remain poorly understood. METHODS The Atherosclerosis Risk in Communities (ARIC) community-based cohort study classified participants using standardized criteria as MCR+/- and mild cognitive

INTRODUCTION Early detection of cognitive decline in older adults is a public health priority. Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA), a multisite study, is validating cognition, emotion, motor, and sensory modules of the National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in the aging spectrum from cognitively

INTRODUCTION Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration. METHODS We examined the effect of intensive (< 120 mm Hg) versus standard (< 140 mm Hg) BP control on longitudinal

BACKGROUND identifying drug-related hospital admissions (DRAs) in older people is difficult. A standardised chart review procedure has recently been developed. It includes an adjudication team (physician and pharmacist) screening using 26 triggers and then performing causality assessment to determine whether an adverse drug event (ADE) occurred (secondary to an adverse drug reaction, overuse, misuse

Growing evidence has suggested that the gut-brain axis plays an important role in the pathogenesis of Parkinson’s disease (PD), and that this role is mediated by the interactions between bile acids (BAs) and intestinal microbiota. Given that cholecystectomy can lead to alterations in BAs and gut microbiota, we investigated whether cholecystectomy is linked to a higher risk of PD. We constructed a cohort

Skin α-synuclein deposition is considered a potential biomarker for Parkinson’s disease (PD). Real-time quaking-induced conversion (RT-QuIC) is a novel, ultrasensitive, and efficient seeding assay that enables the detection of minute amounts of α-synuclein aggregates. We aimed to determine the diagnostic accuracy, reliability, and reproducibility of α-synuclein RT-QuIC assay of skin biopsy for diagnosing

BACKGROUND Gait and cognition decline with advancing age, and presage the onset of dementia. Yet, the relative trajectories of gait and cognitive decline in aging are poorly understood - particularly among those with the Motoric Cognitive Risk (MCR) syndrome. This study compared changes in simple and complex gait performance and cognition, as a function of age and MCR. METHODS We examined gait and

BACKGROUND Hip- and wrist-worn ActiGraph accelerometers are widely used in research on physical activity as they offer an objective assessment of movement intensity across the day. Herein we characterize and contrast key structured physical activities and common activities of daily living via accelerometry data collected at the hip and wrist from a sample of community-dwelling older adults. METHODS

BACKGROUND There is no evidence on the specific beneficial association of the main types of olive oil consumption with frailty. OBJECTIVE The aim was to assess the relationship between olive oil consumption and incident frailty in community-dwelling older adults. DESIGN Prospective cohort. SETTING Participants were recruited in 2008-10 and follow-up through 2013. SUBJECTS In total, 1,896 older adults

Chronological age (CA) is determined by time of birth, whereas biological age (BA) is based on changes on a cellular level and strongly correlates with morbidity, mortality, and longevity. Type 2 diabetes (T2D) associates with increased morbidity and mortality; thus, we hypothesized that BA would be increased and calculated it from biomarkers collected at routine clinical visits. Deidentified data

BACKGROUND COVID-19-related physical distancing measures necessitated widespread adoption of virtual care (i.e. telephone or videoconference), but patients, caregivers and healthcare providers raised concerns about its implementation and sustainability given barriers faced by older adults. OBJECTIVE To describe barriers and facilitators experienced by people accessing and providing virtual care in

BACKGROUND there is little research on preferences in students and newly qualified healthcare professionals for working with people with dementia. Understanding the development of these preferences can help inform strategies to increase workforce capacity in response to current suboptimal dementia care and the increasing numbers of people with dementia. OBJECTIVE to explore the factors that influence

BACKGROUND brain imaging done as part of standard care may have clinical utility beyond its immediate indication. Using delirium as an exemplar, we determined the predictive value of baseline brain imaging variables [white matter changes (WMC) and atrophy] for delirium risk on long-term follow-up after transient ischemic attack (TIA)/stroke in a population-based cohort study. METHODS surviving TIA/stroke

Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP11), has been shown to have rejuvenation and anti-aging properties, but little information is available regarding the role of GDF11 in reproductive system to date. In this study, we first confirmed the bioavailability of recombinant GDF11 (rGDF11) by oral delivery in mice. We also showed that dietary intake of

The community of bacteria that colonize the urinary tract, the urinary microbiome, is hypothesized to influence a wide variety of urinary tract conditions. Older adults that reside in nursing homes are frequently diagnosed and treated for urinary tract conditions such as urinary tract infection (UTI). We investigated the urinary microbiome of older adults residing in a nursing home to determine if

Identification of individuals with increased risk of major adverse cardiovascular events (MACE) is important. However, algorithms specific to the elderly are lacking. Data were analysed from a randomised trial involving 18,548 participants ≥ 70 years old (mean age 75.4 years), without prior cardiovascular disease events, dementia or physical disability. MACE included coronary heart disease death, fatal

Aging-induced pathological alterations of the circulatory system play a critical role in morbidity and mortality of older adults. While the importance of cellular and molecular mechanisms of arterial aging for increased cardiovascular risk in older adults is increasingly appreciated, aging processes of veins are much less studied and understood than those of arteries. In this review, age-related cellular

BACKGROUND Cancer is inversely associated with dementia. Using simulations, we examined whether this inverse association may be explained by dementia diagnosis timing, including death before dementia diagnosis and differential diagnosis patterns by cancer history. METHODS We used multistate Markov simulation models to generate cohorts 65 years of age and free of cancer and dementia at baseline; follow-up

BACKGROUND Indices of multimorbidity and deficit accumulation (i.e. frailty indices) have been proposed as markers of biological aging. If true, changes in these indices over time should predict downstream changes in cognition and physical function, and mortality. METHODS We examined associations that 8-year changes in 1) a multimorbidity index comprised of nine chronic diseases and 2) a frailty index

Substantial variability and severity of dysarthric patterns across Parkinson’s disease (PD) patients may reflect distinct phenotypic differences. We aimed to compare patterns of speech disorder in early-onset PD (EOPD) and late-onset PD (LOPD) in drug-naive patients at early stages of disease. Speech samples were acquired from a total of 96 participants, including two subgroups of 24 de-novo PD patients

INTRODUCTION We examined the temporal sequence of the core features in probable dementia with Lewy bodies (DLB). METHODS In 488 patients with probable DLB, the onset of each core feature and time to diagnosis was determined for men and women, and a pathologic subgroup (n = 209). RESULTS REM sleep behavior disorder (RBD) developed before the other core features in men and women. Men were more likely

Small extracellular vesicles (sEVs) obtained from mesenchymal stromal cells (MSCs) promote neurological recovery after middle cerebral artery occlusion (MCAO) in young rodents. Ischemic stroke mainly affects aged humans. MSC-sEV effects on stroke recovery in aged rodents had not been assessed. In a head-to-head comparison, we exposed young (4–5 months) and aged (19–20 months) male Sprague–Dawley rats

Here we introduce Local Topological Recurrence Analysis (LoTRA), a simple computational approach for analyzing time-series data. Its versatility is elucidated using simulated data, Parkinsonian gait, and in vivo brain dynamics. We also show that this algorithm can be used to build a remarkably simple machine-learning model capable of outperforming deep-learning models in detecting Parkinson’s disease

INTRODUCTION Molecular responses in the brains of persons with mild cognitive impairment (MCI), the earliest transitional state between normal aging and early Alzheimer's disease (AD), are poorly understood. METHODS We examined AD-related neuropathology and transcriptome changes in the neocortex of individuals with MCI relative to controls and temporal responses to the mild hypoxia in mouse brains

INTRODUCTION We aimed to investigate bidirectional associations between cognitive impairment and late age-related macular degeneration (AMD). METHODS Participants in the Age-Related Eye Disease Study 2 (AREDS2) received annual eye examinations and cognitive function testing (e.g., Modified Telephone Interview for Cognitive Status [TICS-M]). We examined bidirectional associations between cognitive impairment

INTRODUCTION People with Down syndrome (DS) are predisposed to Alzheimer's disease (AD). The amyloid hypothesis informs studies of AD. In AD-DS, but not sporadic AD, increased APP copy number is necessary, defining the APP gene dose hypothesis. Which amyloid precursor protein (APP) products contribute needs to be determined. METHODS Brain levels of full-length protein (fl-hAPP), C-terminal fragments

INTRODUCTION Housing insecure veterans are aging, but the prevalence of Alzheimer's disease and related dementias (AD/ADRD) in the population is unknown. METHODS We calculated the prevalence of AD/ADRD diagnoses in 2018 among veterans that experienced homelessness, were at-risk for homelessness, or were stably housed. We determined acute care (emergency department, hospitalizations, psychiatric hospitalizations)

Metabolites, the biochemical products of the cellular process, can be used to measure alterations in biochemical pathways related to the pathogenesis of Alzheimer's disease (AD). However, the relationships between systemic abnormalities in metabolism and the pathogenesis of AD are poorly understood. In this study, we aim to identify AD-specific metabolomic changes and their potential upstream genetic

BACKGROUND Several guidelines have suggested alternative glycemic markers for hemoglobin A1c among older adults with limited life expectancy or multiple coexisting chronic illnesses. We evaluated associations between fructosamine, albumin-corrected fructosamine (AlbF) and fasting plasma glucose (FPG) and mortality in the diabetic and non-diabetic subpopulations, compared which marker better predicts

BACKGROUND Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. METHODS In the U.S and Australia, 19,114 community-dwelling individuals aged ≥70 years (U.S minorities ≥65 years)

BACKGROUND Investigate the longitudinal relationship between physical frailty, the clinical representation of accelerated biological aging, and antidepressant medication response in older adults with depressive illness. METHODS An 8-week randomized placebo-controlled trial (escitalopram or duloxetine) followed by 10-months of open antidepressant medication treatment (augmentation, switch strategies)

Seasonal variation in cognitive function and underlying cerebral hemodynamics in humans has been suggested, but not consistently shown in previous studies. We assessed cognitive function in 10,276 participants from the population-based Rotterdam Study, aged 45 years and older without dementia, at baseline and at subsequent visits between 1999 and 2016. Seasonality of five cognitive test scores and

In this study we investigated how the concentrations, pairwise correlations, and ratios of 202 free circulating blood metabolites and lipids vary with age in a panel of n=1882 subjects ranging from 48 to 94 years. We report a statistically significant sex-dependent association with age of a panel of metabolites and lipids involving, in women cohort, linoleic acid, α-linoleic acid, and carnitine, and

BACKGROUND Emerging evidence showed that bone metabolism and cardiovascular diseases (CVD) are closely related. We previously observed a potential immediate risk of cardiovascular mortality after hip fracture. However, whether there is an immediate risk of cardiovascular events after hip fracture is unclear. The aim of this study was to evaluate the risk for major adverse cardiovascular events (MACEs)

Epidemiological studies report beneficial associations of higher educational attainment (EDU) with Alzheimer’s disease (AD). Prior genome-wide association studies (GWAS) also reported variants associated with AD and EDU separately. The analysis of pleiotropic associations with these phenotypes may shed light on EDU-related protection against AD. We performed pleiotropic meta-analyses using Fisher’s

The elderly population is the most susceptible to SARS-CoV-2 infection and develops the worst clinical phenotype with severe pneumonia and cardiac complications. Older COVID-19 patients are also at higher risk of sudden death, mainly attributable to electrolyte disorders and to an uncontrolled inflammatory response. After the identification of ACE 2 as the receptor of SARS-CoV-2 in human cells, several

The study of immune system aging is of relevance, considering its myriad of interactions and role in protecting and maintaining body homeostasis. While mouse models have been extensively used to study immune system aging, little is known on how the main immune populations progress over time and what is the impact of sex. To contribute to filling this gap, male and female BALB/cByJ mice were longitudinally

The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multi-national, population-based multi-generational family study of the genetic and non-genetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (2006-2009) recruited 4,953 individuals from 539 two-generation families, selected from the upper 1% tail of the Family Longevity Selection Score

BACKGROUND Half of all physical disability, including activity of daily living (ADL) disability, among older adults occurs in the setting of hospitalization. This study examines whether appendicular lean mass (ALM) and grip strength, which are commonly included in various definitions of sarcopenia, are associated with development of hospital-associated ADL disability in older adults in the Health ABC

Dicarbonyl stress describes the increased formation of 1,2-dicarbonyl compounds and is associated with age-related pathologies. The role of dicarbonyl stress in healthy aging is poorly understood. In a preliminary study, we analyzed 1,2-dicarbonyl compounds, namely 3-deoxyglucosone (3-DG), glyoxal (GO) and methylglyoxal (MGO) in plasma of older (25 months, n=11) and younger (5 months, n=14) male C57BL/6J

AMP-activated protein kinase (AMPK) is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. AMPK is currently considered a promising target for preventing age-related diseases. Rubidium is one of the trace elements in human body. As early as the 1970s, RbCl has been was reported to have neuroprotective effects. In this work, we report the anti-aging effect

Methods to quantify biological aging are emerging as new measurement tools for epidemiology and population science and have been proposed as surrogate measures for healthy lifespan extension in geroscience clinical trials. Publicly available software packages to compute biological aging measurements from DNA methylation data have accelerated dissemination of these measures and generated rapid gains

There is an urgent need for interventions that can prevent or delay cognitive decline and dementia. Decades of epidemiological research have identified potential pharmacological strategies for risk factor modification to prevent these serious conditions, but clinical trials have failed to confirm the potential efficacy for such interventions. Our multidisciplinary international group reviewed seven

INTRODUCTION We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study). METHODS Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment

The role of cellular senescence in the development of asthma is not well known. We aimed to evaluate the susceptibility of mice with cellular senescence to asthma development and determine whether the mTOR pathway played an important role in this process. Cellular senescence was induced in mice by intranasal instillation of 2% cigarette smoke extract (CSE). Subsequently, a low dose (0.1 μg) of house

Age-dependent differences in methylation at specific cytosine-guanosine sites (CpGs) have been used in “epigenetic clock” formulas to predict age. Deviations of epigenetic age from chronological age are informative of health status and are associated with adverse health outcomes, including mortality. In most cases, epigenetic clocks are performed on methylation from DNA extracted from circulating blood