Delirium is a serious neuropsychiatric condition that lacks an effective treatment intervention. A confusional state often brought on by acute illness, delirium is associated with acute inflammation and metabolic dysfunction. NAD+ is a metabolite involved in both cellular energy generation and immunomodulation, that has previously been found to promote metabolic function and reduce inflammation. Whether

Growth-differentiation factor 15 (GDF15), a cytokine with the ability to regulate metabolic and inflammatory activity, is negatively associated with physical and cognitive function, and increases in circulation with age. Mechanistically, the expression of GDF15 is stimulated by mitochondrial stress across multiple tissues. We hypothesized elevations in basal circulating GDF15 were negatively associated

Background Sensory and cognitive function can impact physical performance, but the relationship of multiple sensory impairments (SIs) with mobility in older adults is not well understood. We hypothesized that severity and number of SIs would be associated with worse timed physical mobility performance, and that cognitive processing speed would mediate the association. Methods Participants (N = 832)

Background Previous studies have identified links between air pollution, insulin resistance (IR), and hypertension risk, but the mediating role of IR in the relationships between air pollution exposure and hypertension remains unexplored. Methods This national cross-sectional study included 10,405 middle-aged and older adults from 120 Chinese cities. Long-term air pollution exposure was estimated using

Aging varies across individuals, highlighting the need for better markers of functional decline. This study investigates the hypothesis that T cell energy metabolism is correlated with functional health in older adults. We used flow cytometry-based profiling to examine energy metabolism, focusing on mitochondrial OXPHOS activity (MitoDep, expressed as percentage), in peripheral CD4 and CD8 T cell subsets

Background Laboratory studies have demonstrated that mice with α-klotho gene deficiency experience a shortened lifespan, but epidemiological evidence linking circulating α-klotho levels and mortality remain inconclusive. This study aimed to examine the association between α-klotho and mortality and to explore how liver fibrosis mediate this association. Methods The participants were selected from the

Background The association of metformin with mortality has been mixed, and no prior study has determined whether metformin initiation is associated with exceptional longevity, defined as survival to ages 90 and older. Methods We performed a new-user, active comparator cohort study using the target trial emulation framework among the Women’s Health Initiative cohort to determine whether metformin versus

BACKGROUND This study aims to assess the evolution of cognitive performances over a five-year follow-up period in community-dwelling older people with negative plasma p-tau181 levels and to determine whether frailty could discriminate between those who experience cognitive decline and those who do not, in the p-tau negative groups. METHODS This is a five-year analysis of the Multidomain Alzheimer Prevention

Geroscience is an emerging interdisciplinary field that explores the biological connections between aging and the development of chronic diseases, with the ultimate goal of identifying interventions to extend healthspan and delay age-related conditions. Recognizing the growing importance of this field, the Canadian Translational Geroscience Network (CTGN, geroscience.ca) was officially launched during

BACKGROUND Temporal relationships between physical and cognitive decline with aging are poorly understood, and little is known about the underlying mechanisms linking these conditions. We hypothesized that plasma biomarkers of Alzheimer’s disease and related dementias (ADRD) may be associated with mobility performance in older adults who are cognitively unimpaired. METHODS We constructed separate linear

Despite the growing burden of knee osteoarthritis (KOA) on aging populations, our mechanistic understanding of this disease remains lacking. Though KOA is a whole joint disease, the impact of intra-articular structures, like the infrapatellar fat pad (IFP), on cartilage health is unclear. This study investigated the effect of age on paracrine communication between IFPs and chondrocytes. To isolate

BACKGROUND Long COVID incidence and risk factors in older adults need to be better characterized to identify risk mitigation strategies. Our aim was to quantify the incidence of Long COVID in a population-based sample of older adults and to describe the association between COVID-19 vaccination and Long COVID risk. METHODS This cohort study included Medicare fee-for-service beneficiaries ≥ 66 years

Background Changes in the immune system are a potential biological mechanism of aging. We investigated the association of circulating immune cell subsets with age at death and survival to age 90. Methods Immune cell phenotypes were measured at baseline in 1,625 adults, aged 70 to 85 years, in the Cardiovascular Health Study. We selected five primary immune cell subsets: gamma-delta T-cells, natural

Background Promoting cognitive health and preventing deficits is crucial for improving the population level health and reducing economic burdens. Biological aging, influenced by DNA methylation (DNAm), plays a key role in predicting cognitive performance and brain aging. A more recent body of literature shows that social engagement, and volunteering in particular, may play an important role in modifying

Background Although gait speed typically declines with age, some individuals manage to maintain higher walking speeds well into older age. To better understand healthy longevity, we propose a novel exceptional aging phenotype of super movers, individuals 80 years or older with walking speeds comparable to individuals three decades younger. Methods We conducted a retrospective cohort study to examine

Beyond their essential roles in regulating reproduction and development, sex hormones play a crucial role in the aging processes. Observational studies have indicated that low sex hormone concentrations in older age are associated with adverse health events. DNA methylation age acceleration (DNAmAA) estimated from epigenetic clocks quantifies differences in biological aging. DNAmAA was previously shown

Background PM2.5 pollution is expected to worsen in many places due to climate change, as a result of hotter temperatures, less precipitation, and increases in wind speed. PM2.5 exposure has adverse effects on humans that may accelerate the aging process, such as worsening cognitive functioning and cardiometabolic disease. Less is known about whether physical and mental health conditions mediate the

Background Physical resilience (PR), the ability to recover from health adversities, is thought to buffer health challenges during aging. However, PR’s association with mortality and its ability to offset the negative effects of genetic susceptibility to shorter lifespan remain unknown. Methods Data on 3,041 individuals (age: 60+) from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K)

Oxidative stress and mitochondrial dysfunction are proposed to play prominent roles in the biology of aging. Human studies are limited and confounded by metabolic disturbances associated with age-related diseases. In this study we have measured biomarkers of oxidative and mitochondrial stress in blood samples from up to 864 participants in the longitudinal Dunedin Multidisciplinary Health and Development

Background Emerging research suggests the potential combined effects of statin medication and fine particulate matter exposure on cardiovascular disease (CVD) risk among older adults. These findings underscore the need for further detailed investigations. This cohort study aims to examine the combined effects of adherence to statins and particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) exposure

BACKGROUND Intentional weight-loss improves physical function among older adults with obesity, despite the associated lean mass loss. However, prior studies have not assessed impacts of weight-loss on physical function and body composition among older adults with type 2 diabetes mellitus (T2DM) and obesity, a population at high-risk for sarcopenia and functional decline. Our objective was to examine

Background Past research has highlighted the association of family longevity, support, functioning, and health and well-being factors in predicting longevity. Based on the Georgia Adaptation Model that examined the impact of clusters of bio-psycho-social predictors on extreme longevity and adaptation, the current study aimed to employ seven clusters of behavioral and social predictors on longevity

Background Identifying effective risk assessment strategies and prediction models for frail populations is crucial for precise mortality risk identification and improved patient management. This study aimed to evaluate whether prediction models incorporating survey data combined with biomarkers, physical measurements, or both could enhance mortality risk prediction in frail individuals than survey-only

Background Visual contrast sensitivity (CS) is critical to many functions in older adults and is associated with brain network community structure, but the direction of the relationship between CS and the brain remains unclear. Methods We evaluated whether baseline binocular CS predicts 30-month functional brain network organization in 172 community-dwelling older adults (mean age 76.4±4.8 years, 56

BACKGROUND The Claims-based Frailty Index (CFI) has been developed and validated using Medicare claims data. However, whether CFI can be applied to structured EHR data has not been studied. METHODS We applied the CFI to a structured EHR dataset (Explorys dataset) and a Medicare fee-for-service (FFS) 5% sample data and compared the prevalence of frailty from each dataset, using the cohort of older adults

Prior research has examined associations of exposure to air pollution and heat with epigenetic alterations separately; however, these two exposures commonly used to measure climate change typically co-occur. We examine joint effects of exposure to elevated PM2.5 and heat on DNA methylation (DNAm). Data come from the 2016 Health and Retirement Study DNAm Sample (N=3,947) and census tract level annual

Background Although regular visits to dentists improve oral health status, few studies have reported an association between dental checkups and all-cause mortality in older adults. This 3-year retrospective cohort study aimed to clarify an association between dental checkups and all-cause mortality in older adults. Methods A total of 946,709 older adults aged ≥75 years, community-based residents in

The decrease of tissue resiliency with aging is due, in part, to changes in the retention of stem cell/progenitor populations that act to restore and maintain tissue quality with age or injury. In mice, the Celsr1 gene has been identified as a regulator of quiescent stem cells, while in zebrafish, celsr1a mutants demonstrate an essential function in maintaining adult stem cell populations within the

Background Excessive daytime sleepiness (EDS) and long sleep duration are common in older adults and are related to dementia pathology. This study aims to assess the effect of EDS and long sleep duration on all-cause dementia and cognitive decline. Methods We identified longitudinal studies assessing the relationship between EDS and/or long sleep duration on cognitive decline/dementia published up

Background Older adults with exceptional longevity – and their offspring – are protected from age-related diseases and have a prolonged health span. Prior research suggests that offspring of parents with exceptional longevity have larger temporal and sensorimotor cortices in mid to late-adulthood – but the association between brain health and parental longevity is not well understood in older adults

Background Previous epidemiological studies have revealed a relationship among planetary health diets (PHDs), diet-related greenhouse gas emissions (GHGEs), and mortality. However, these studies did not include older adults from non-Western countries. This study examined these associations in Japanese older adults. Methods This prospective study included 8043 adults aged ≥65 years from the Kyoto–Kameoka

BACKGROUND Benign prostatic hyperplasia (BPH) is a widely observed disorder in older men, with substantial evidence indicating that cellular senescence serves a pivotal function in its progression. This investigation seeks to pinpoint cellular senescence-related genes causally connected with BPH and to examine their expression and regulatory networks across distinct prostate cells. METHODS Using exposure

Background Type 2 diabetes (T2D) is characterised by elevated levels of metabolic and inflammatory markers but less is known about other molecular alterations that occur with ageing. We aimed to assess the associations of DNA methylation-based measures of ageing (epigenetic ageing) with prevalent and incident T2D in a large sample of middle-aged and older Australians. Methods We used data from 5403

Subclinical depression is common in older adults, especially in females, and may correlate with a higher likelihood of health events and poor prognosis. However, the underlying neurobiology remains unclear. This study, employing resting-state functional magnetic resonance imaging (rs-fMRI), identified alterations in temporal dynamics of intrinsic brain activity in older women with subthreshold depression

Background Recent epidemiological studies have linked the central nervous system (CNS) to osteoarthritis (OA), suggesting that targeting the CNS could offer new therapeutic strategies. This study aimed to validate the correlation between brain structures and OA risk, and to identify key causal genes by integrating brain transcriptomic and proteomic data with OA genome-wide association studies (GWAS)

Cardiorespiratory fitness declines with ageing and is a major risk factor of cardiometabolic diseases and early death. Although the benefits of regular exercise are well established, whether maximal oxygen uptake (V̇O2max) is associated with biological ageing remains unclear. Given that telomere shortening is a hallmark of ageing, the purpose of this systematic review and meta-analysis was to determine

Background The association of cumulative blood pressure (BP) with progression rate of depressive symptoms and functional impairment remained largely unknown, and this study aims to explore whether higher cumulative BP is associated with a faster rate of aggravation of depressive symptoms and functional impairment. Methods This longitudinal cohort study adopted data from the English Longitudinal Study

Background Despite the rising global burden of mental disorders, their impact on complication risk following hip fracture surgery remains unclear. We examined reoperation and mortality risks after hip fracture surgery, investigating patients with and without moderate to severe mental disorders. Methods Using a nationwide cohort design, we identified patients undergoing hip fracture surgery from the

Background Physical activity (PA) engagement declines with age in late adulthood. Therefore, understanding factors underlying PA engagement is needed for PA promotion in older adults. Executive function is a potential key neurocognitive resource that supports PA engagement. The current study aims to provide neurobiological evidence for this hypothesis by examining the role of the executive function

BACKGROUND Falls are the leading cause of accidental injury among older adults. Current fall prevention programs are useful but do not target the key variable for injury (i.e., impact force). An approach, which has shown promise in robust older adults, is to teach safe-falling strategies to reduce impact forces. In this single-blinded, pilot randomized controlled trial, we explored the feasibility

Background Some short-term vitamin D supplementation trials suggest benefits on cognitive performance, but apart from observational studies, there is little evidence whether long-term vitamin D supplementation can prevent development of dementia. We investigated whether vitamin D3 supplementation could affect the incidence of diagnosed dementia in a generally healthy population. Methods The study included

The age-related loss of muscle mass is partly driven by a reduction in serial sarcomere number (SSN), and further SSN loss occurs during immobilization. SSN is associated with optimal force and power production and muscle passive tension, thus immobilization-induced SSN loss is especially a concern for older individuals who are often subjected to forced muscle disuse with illness and injury. We previously

BACKGROUND Most population-based studies and clinical fall-risk screenings depend on self-reported balance information. This study investigated the congruency between self-reported balance information and performance-based balance measure (Romberg Test of Standing Balance on Firm and Compliant Support Surfaces, RTSBFCSS). It also explored predictors of congruency between these balance measures. METHODS

Increased cellular damage in aging tissues releases circulating cell-free genomic DNA (ccf-gDNA) into the bloodstream, and these fragments are associated with a higher risk of frailty and dementia. We hypothesized that identifying the tissue of origin for ccf-gDNA using methylation signatures can distinguish subgroups of participants with distinct clinical outcomes, biological aging rates, and energy

Background The pathophysiology of delirium remains incompletely understood. The relationship between preoperative plasma concentrations of p-tau181, p-tau231, p-tau217, and T-tau proteins and postoperative delirium needs further validation. We aimed to verify whether these markers can identify and predict the occurrence and severity of postoperative delirium. Methods 172 older adults undergoing laparoscopic

Background To investigate whether differences between motoric cognitive risk syndrome (MCRS) and mild cognitive impairment (MCI) are of vascular origin, we compared the risk of incident cardiovascular disease in both groups in a population-based study. Methods We included 2710 dementia-free participants of the Rotterdam Study who underwent structured interviews, as well as gait and cognitive assessments

Background Assessing older drivers’ fitness-to-drive (FTD) is challenging, with decisions impacting mobility and health. This study aimed to validate the Candrive older driver risk stratification tool (RST) for screening medical FTD in an independent cohort of older adults from the Ozcandrive 8-year prospective study. Methods A convenience sample of drivers aged 75 and older residing in Melbourne,

Heterogeneity in aging is a fundamental biological process arising from multifactorial etiologies, including genetic, lifestyle, and socioeconomic factors. Modeling this heterogeneity in animal systems is critical for elucidating the underlying mechanisms of aging and for leveraging these insights in translational research. Here we present part II, a summary of the model organism research presented

Background The COVID-19 pandemic has had a profound impact on older adults, particularly those with existing comorbidities. To inform targeted healthcare strategies for this heterogeneous group, this study seeks to analyze and compare mortality trends among various geriatric age groups within the Veterans Affairs (VA) Health Care System, both during the COVID-19 era and the pre-COVID era, while accounting

The ABCB1 gene, encoding the ATP-dependent translocase ABCB1, plays a crucial role in the clearance of amyloid-beta (Aβ) peptides and the transport of cholesterol, implicating it in the pathogenesis of Alzheimer's disease. The study aims to investigate the association between polymorphisms in the ABCB1 gene and cognitive decline in individuals with MCI, particularly focusing on language function. A

Ageing-associated cognitive decline affects more than half of those in long-term residential aged care. Emerging evidence suggests that gut microbiome-host interactions influence the effects of modifiable risk factors. We investigated the relationship between gut microbiome characteristics and severity of cognitive impairment CI in 159 residents of long-term aged care. Severe CI was associated with

There is an urgent need to develop tools enabling older adults to live healthy, independent lives as long as possible. To address this need, the National Institute on Aging (NIA) Artificial Intelligence and Technology Collaboratories (AITC) for Aging Research were created to identify, develop, evaluate, commercialize, and disseminate innovative technologies and artificial intelligence (AI) methods

Scientific progress depends on the generosity of reviewers who assist editors by sharing their time and expertise in the peer review process. Lewis Lipsitz, Editor-in-Chief of The Medical Sciences Section of the Journal of Gerontology Series A, on behalf of the editorial leadership team, wishes to thank the following individuals for their assistance in reviewing manuscripts during 2024.

Background Emerging evidence supports the central role of the immune system in brain health, yet little is known about the role of circulating immune cells and cognitive function or brain health in dementia-free populations. We investigated the association of 43 immune cells with cognitive function, structural brain imaging, and incident dementia in Framingham Heart Study Offspring participants. Methods

Background Metabolic-inflammatory states are central to multiorgan mechanisms of aging, but precise functional biomarkers of physiological aging remain less clear. Methods In the Health, Aging and Body Composition study, we defined metabolomic profiles of the Healthy Aging Index (HAI), a composite of cardiovascular, lung, cognitive, metabolic, and renal function (0-10, with higher scores indicating

: Background The potential impacts of drug-induced modulation of mitochondrial function in humans remain unclear despite the high prevalence of “mito-modulatory” medication use among older adults. While these medications, such as statins and metformin, have undergone extensive characterization of their effects on mitochondrial function in vitro, the effects in humans are far more complex and poorly

Background Previous studies have reported an association between multimorbidity and cognitive function, however, the specific direction and underlying mechanism remain unclear. The study aimed to explore the direction of this association and to examine the role of physical activity and leisure activity among older adults. Methods Data from 5,546 dementia-free Americans aged 60 or above of 2008 (T1)

Background To investigate the potential role of lactate in the relationship between periodontitis and biological aging. Methods Cross-sectional data from 9,652 participants in the National Health and Nutrition Examination Survey 2009-2014 were analyzed. Periodontitis was categorized based on the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC/AAP) classification

Background The Life’s Essential 8 (LE8) is a composite metric including four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure). This study aimed to describe the cardiovascular health (CVH) metrics promoted by LE8 in nonagenarians and to investigate their relationship

The active peptide hormone Ang II (angiotensin II) mediates the vast majority of the RAS (renin-angiotensin system) action, mainly through activation of AT1R (Angiotensin II type-1 receptor). AT1R expression peaks in newborn males and decreases toward the adult age, and it is shown to exhibit an inhibitory effect on hCG (human chorionic gonadotropin)-stimulated steroidogenesis in LCs (Leydig cells)