Aging & Longevity

Singapore's rapidly aging population and increasing healthcare demands highlight the need for projections to inform policy planning. Here we adapted a previously published dynamic Markov microsimulation model, the Future Elderly Model, to estimate disease trajectories and healthcare expenditure among adults aged 51 years and older in Singapore. The model simulated four long-term lifestyle interventions aligned with the Healthier SG program from 2020 to 2050. Our projections indicate an...

Aging is associated with the accumulation of molecular damage, functional decline, increasing disease prevalence, and ultimately mortality. Although our system-wide understanding of aging has significantly progressed at the genomic and transcriptomic levels, the availability of large-scale proteomic datasets remains limited. To address this gap, we have conducted an unbiased quantitative proteomic analysis in male C57BL/6J mice, examining eight key organs (brain, heart, lung, liver, kidney,...

More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions....

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from...

Aortic stenosis (AS) is the most prevalent valve disease in developed countries, with its incidence rising in the aging population. The current criteria for aortic valve replacement (AVR) are based on subjective symptoms and left ventricular ejection fraction (LVEF), which may not adequately reflect left ventricular (LV) dysfunction. This highlights the necessity for objective biomarkers to evaluate subclinical LV dysfunction. Serum angiotensin-converting enzyme 2 (sACE2) has emerged as a...

Nicotinamide riboside (NR) is a precursor to NAD^(+), a vital molecule for cellular energy metabolism whose levels decline with age. Aging is associated with loss of cognitive and immune function, alterations in hematological parameters, and increased vulnerability to stress. Although NR supplementation can mitigate age-related declines, it remains uncertain whether these positive effects persist when the organism is exposed to chronic physiological stress. We investigated this by exposing aged...

BACKGROUND: Frailty is a significant clinical syndrome affecting aging populations, leading to increased risks of negative outcomes such as falls, disability, hospitalization, and premature mortality. The concept has evolved from a simplistic view to a complex view that incorporates physical, psychological, cognitive, and social domains. Early intervention is crucial, yet research on the interactions among these domains is limited. This study protocol aims to outline various combinations of...

BACKGROUND: Frailty is the deterioration of physiological functions due to aging, linked to negative outcomes. Frailty, being a reversible and dynamic state, calls for individualized and comprehensive management. Goal Attainment Scaling (GAS) is a personalized method for establishing and assessing progress towards individual goals, suitable for older adults with complex requirements. We focus on attaining personalized intervention goals for elderly patients with frailty, correcting frailty...

During cognitive tasks, older adults often show increased frontoparietal neural activity and functional connectivity. Cognitive reserve accrued from positive life choices like long-term musical training can provide additional neural resources to help cope with the effect of aging. However, the relationship between cognitive reserve and upregulated neural activity in older adults remains poorly understood. In this study, we measured brain activity using functional magnetic resonance imaging...

Attenuating protein synthesis promotes longevity in multiple species. However, numerous studies indicate that aging drives a decrease in protein synthetic capacity. These observations hint at potential, unexplored benefits of stimulating protein synthesis in old age. In this work, we focus on Maf1, a repressor of protein synthesis genes transcribed by RNA Polymerase (Pol) III, such as the 5S rRNA and tRNAs, and its role in aging. We show that the knockdown of Maf1 extends lifespan in Drosophila....

Macroautophagy/autophagy activation protects renal proximal tubular epithelial cells (PTECs) against acute kidney injury (AKI) induced by various challenges. The mechanism that regulates autophagy in PTECs, however, remains incompletely understood. Here, we report that VMP1 (vacuole membrane protein 1) plays an essential role in enabling PTECs to maintain high autophagic flow under AKI conditions. VMP1 in PTECs is strongly upregulated in AKI patients but not chronic kidney disease patients. The...

We know vanishingly little about how long-lived apes experience senescence in the wild, particularly with respect to their foraging behaviors. Chimpanzees use tools during foraging, and given the cognitive and physical challenges presented by tool use, tool-use behaviors are potentially at a heightened risk of senescence, though this has never been investigated in wild individuals. Accordingly, we sampled data from a longitudinal video archive that contained footage of wild chimpanzees using...

Aging is a complex biological process driven by genetic and immune-mediated mechanisms, yet the causal roles of immune-cell-specific gene regulation remain unclear. In this study, we integrate single-cell expression quantitative trait loci (sc-eQTL) data with Mendelian randomization (MR) and colocalization analyses to identify immune-mediated regulatory mechanisms and therapeutic targets for aging. Using data from 14 immune cell types, we systematically evaluated 8733 eGenes for causal effects...

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To understand observed spatial distributions of white-matter (WM) aging, developmentally driven theories termed "retrogenesis" have gained traction, positing that WM tract development order predicts order of declines, with later developing regions expected to deteriorate first, i.e., "last-in-first-out." Alternatively, regions that develop most rapidly may decline most rapidly in aging, i.e., "gains-predict-loss." The validity of such theories remains uncertain, partly due to lack of clarity in...

Sporadic Alzheimer's disease and some forms of frontotemporal lobar degeneration (FTLD-tau) are neurological disorders of later life where cognitive deficits follow from the progressive accumulation of microtubule-associated tau protein. Disease-related tau accumulation is marked by altered subcellular distribution and rearrangement of this natively unstructured protein into alternative conformational forms, including highly organized fibrillar assemblies. With a partial analogy to effects seen...

CONCLUSIONS: Depressive symptoms moderated the mediation of ADL on an indirect, negative correlation between DSI and SP. The findings contribute to existing knowledge by illustrating the fundamental mechanisms connecting DSI and SP. These Findings highlight the need for integrated interventions targeting both sensory impairment and mental health to mitigate SP decline in aging populations.

CONCLUSION: The study adds to a growing body of research demonstrating the feasibility and utility of online cognitive testing for reaching large cohorts of individuals across the adult lifespan. We report findings that mirror the existing literature on cognitive aging, but also provide unique insights into the trajectory of cognitive functioning. We discuss the benefits, challenges, and future promise of web-based testing.

CONCLUSIONS AND IMPLICATIONS: This study highlights how capitation rates positively influence care quality in nursing homes within the MLTSS context. The findings provide valuable insights for policymakers, health care administrators, and managed care organizations seeking to optimize care quality in MLTSS programs.

Patient genomics and mouse functional genetics have revealed that senescence is a barrier to metastatic progression of prostate cancer. Many efforts focus on eliminating senescent cells, whereas others aim to elucidate distinct characteristics that set them apart from normal and aging cells. Here, we discuss how exploration of the redox state of senescent cells could help define new markers and pro-oxidant vulnerabilities, drawing analogy to what is known about the redox sensitivity of...