Aging & Longevity

CONCLUSIONS: DS are common in later life and are frequently persistent. Minor DS often persist or worsen, underscoring their role as a key risk factor. Major DS frequently remits only partly. Early, targeted interventions could be informed by modifiable determinants that may also help to allocate scarce mental health resources effectively.

The growing epidemiological burden of multimorbidity among older adults underscores an urgent need to develop interventions that can address multiple age-related diseases (ARDs) at once. Yet, the biological mechanisms driving their co-occurrence remain poorly understood. In this study, we conducted a multivariate genome-wide association analysis to dissect the shared genetic architecture of five common ARDs: heart attack, high cholesterol, hypertension, stroke, and type 2 diabetes. We defined...

Aging is a complex biological process characterized by molecular changes across multiple biological scales. While these alterations have been extensively studied in humans and rodents, the molecular changes associated with aging in dogs remain underexplored despite their relevance as a model for human aging. In this study, we profiled gene expression (n = 16,273 genes) and protein abundance (n = 2041 proteins) in whole blood and blood plasma from 40 laboratory beagles across young (3-5 years...

Olfactory impairment is common in older age and is a known early feature of several dementia diseases. Blood-based biomarkers of Alzheimer's disease (AD) now offer a scalable method for detecting pathophysiological mechanisms related to olfactory decline in the general population. However, few studies have examined how these biomarkers relate to long-term olfactory trajectories. Most existing work has been limited to cross-sectional settings. In this population-based study, we used biomarker...

Decreased resting cerebral blood flow and cerebrovascular reactivity (CVR) are important age-related factors associated with an increased risk of stroke or dementia. However, these declines may be exaggerated by a sedentary lifestyle or blunted by engaging in more aerobic-based physical activity. The objective of the present project was to explore differences in resting middle cerebral artery velocity (MCAv), CVR, moderate-to-vigorous intensity physical activity (MVPA), light-intensity physical...

Aging significantly impacts motor performance, especially in multi-joint movement tasks where the nervous system needs to adequately coordinate mechanical interactions between joints. Effective coordination of multiple joints relies on intact feedforward control to predict movement dynamics in the initial phase of the movement, and on feedback control to fine-tune the execution in the final phase. The effect of aging on these specific control mechanisms remains controversial. Here, we...

CONCLUSIONS: Pair 2 Care may provide an innovative strategy to improve family caregiver health outcomes such as quality of life among Black caregivers of Black people living with dementia to promote health equity. As a next step, a fully powered trial is needed to determine Pair 2 Care intervention efficacy.

The global aging of the population, coupled with an increasing prevalence of sedentary lifestyle and overnutrition, is fueling an alarming rise in the worldwide obesity rates. Besides its well-known bodily consequences, obesity is increasingly recognized as a risk factor for cognitive impairment, dementia, mood disorders, and emotional distress, suggesting a possible role of adiposity in the pathogenesis of both neurodegeneration and neuropsychiatric diseases. Despite the growing research...

The etiopathogenesis of Parkinson's Disease (PD) remain poorly understood, particularly the roles of aging and the gut-brain axis. This study investigated the impact of aging on the development of PD hallmarks, including neurodegeneration and inflammation, in both the central (CNS) and enteric (ENS) nervous system of mice following exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Young (2-4 months) and adult (7-12 months) mice were treated with either saline or MPTP (four...

The significance of DNA hydroxymethylation in replicative senescence of mesenchymal stem cells (MSCs) and aging-related osteoporosis remains unknown. Here, we reveal 5hmC levels positively regulate MSC self-renewal and osteoblast differentiation. Mechanistically, PARP1 recruits TET1 to hydrolyze methylated nucleotides on DNMT1 exons, aiding CTCF in preventing DNMT1 alternative splicing in early MSCs. Additionally, ATM phosphorylates TRIM37 at Th203, promoting its nuclear entry and the...

Epigenetic Clocks have been trained to predict chronological age, healthspan and lifespan. Such clocks are often analysed in relation to disease outcomes - typically using small datasets and a limited number of clocks. Here, we present a large-scale (n = 18,859), unbiased comparison of 14 widely used clocks as predictors of 174 incident disease outcomes and all-cause mortality over 10-years of follow up. Second- and third-generation clocks significantly outperform first-generation clocks, which...

The central nervous system, comprised of the brain, spinal cord, and nerves, includes the autonomic nervous system (ANS) that regulates involuntary functions. Within the ANS, the sympathetic and the parasympathetic nervous systems (SNS and PNS, respectively) control the same bodily functions, but in opposing directions. For example, the sympathetic nervous system elicits our "fight or flight" response, while the parasympathetic system supports "rest and repair" mechanisms in the broadest...

N6-methyladenosine (m⁶A) is the most prevalent RNA modification and plays diverse roles in mammalian cells. However, its significance in human trophoblast lineage commitment and placenta development remains poorly understood. Here we show that METTL3, the primary enzyme responsible for m⁶A depositions, specifically marks cytotrophoblasts in human placenta, and exhibits defective expression in cytotrophoblasts from preeclampsia patients. Through in-depth in vitro investigation, we identify...

Battery health often evolves from an initial regime of slow capacity decay to a fast decay regime, due to catastrophic electrochemical reactions to cause the battery failure. The signals of such failure, however, often emerge much earlier during cycling, an early detection of which may help prevent the failure through real-time adjustment of cycling procedures. Here we demonstrate the integration of machine learning module directly into electrochemical battery test stations to constantly detect...

Senescent cells, characterized by a state of irreversible proliferative arrest and inflammatory profile, have emerged as drivers of age-related decline. Growing evidence suggests that alterations in mitochondrial function and morphology play a key role in the induction and maintenance of senescence, as well as in promotion of the proinflammatory senescence-associated secretory phenotype (SASP). In this review, we seek to survey the relationship between mitochondrial dysfunction and senescence,...

Single-cell multiomics provides critical insights into how disease-associated variants identified through genome-wide association studies (GWASs) influence transcription factor eRegulons within a specific cellular context; however, the regulatory roles of genetic variants in aging and disease remain unclear. Here, we present scMORE, a method that integrates single-cell transcriptomes and chromatin accessibility with GWAS summary statistics to identify cell-type-specific eRegulons associated with...

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CONCLUSIONS: Cumulative risks during the COVID-19 pandemic escalated, with pandemic responses such as lockdowns increasing the adverse effects of social isolation and loneliness on positive affect of very old adults. Our pooled-multi-sample design allows a quantitative investigation of an understudied population, offering researchers new insights and an empirical strategy to utilize.

CONCLUSIONS: Incident diabetes was associated with accelerated progression of frailty in older adults, particularly in the domain of instrumental activities of daily living. Regular functional assessments and targeted interventions following diabetes diagnosis was important, especially for high-risk subgroups including the oldest-old, unmarried individuals, and those with lower BMI.

Brain aging can cause cognitive and motor disabilities which often correlate with changes in dendritic branch, axon collateral, and synapse numbers. However, from invertebrates to mammals, age-related decline is typically restricted to specific neuron types or brain parts, indicating differential vulnerability. The rules to pinpoint the susceptibility of distinct brain elements to aging remain largely unknown. Here, we combine longitudinal studies with neuroanatomical, electrophysiological, and...