Aging & Longevity

In aging cells and animal models of premature aging, heterochromatin loss coincides with transcriptional disruption including the activation of normally silenced endogenous retroviruses (ERVs). Here we show that loss of heterochromatin maintenance and de-repression of ERVs result in a chronic inflammatory environment characterized by neurodegeneration and cognitive decline in mice. We identify distinct roles for HP1 proteins to ERV silencing where HP1γ is necessary and sufficient for H4K20me3...

Aging and cognitive impairment increase the risk for Alzheimer's disease (AD), and growing evidence suggests that transposable elements (TEs) in the genome play a role in aging and AD. The mechanisms of TE dysregulation in this context are unclear, but one possibility is that epigenetic changes, including DNA hypomethylation and/or reduced chromatin structure, underlie age- and AD-related TE activity. Therefore, the purpose of the present study was to generate a resource for studying TE...

The weight-adjusted waist index (WWI) is a novel anthropometric measure designed to better reflect central obesity than traditional indices such as body mass index and waist circumference (WC). This study examined the prospective association between WWI and cardiometabolic multimorbidity (CMM) and evaluated its predictive utility. We included 3,348 participants (mean age 63 years; 45.1% male) from the English Longitudinal Study of Ageing who were free from hypertension, coronary heart disease,...

People with dementia have complex medical, functional, and social needs and experience highly variable care quality and outcomes across the U.S. health care system. Community-based physicians, nurse practitioners, and physician assistants serve critical roles in diagnosing and managing dementia, yet little is known about this workforce and factors contributing to variability in care. The National Dementia Workforce Study (NDWS), sponsored by the National Institute on Aging, is conducting large...

CONCLUSION: Older adults who regularly play cards/mahjong have a lower risk of all-cause mortality, especially in the oldest groups. These leisure activities may promote longevity, but further research is needed to understand why.

Discrete genomic units can recombine into composite transposons that transcribe and transpose as single units, but their regulation and function are not fully understood. We report that composite transposons harbor bivalent histone marks, with activating and repressive marks in distinct regions. Genome-wide CRISPR-Cas9 screening, using a reporter driven by the hominid-specific composite transposon SVA (SINE [short interspersed nuclear element]-VNTR [variable number of tandem repeats]-Alu) in...

Metal anodes hold considerable promise for high-energy-density batteries but are fundamentally limited by electrochemical irreversibility caused by uneven metal deposition and dendrite formation, which compromise battery lifespan and safety. The chaotic ion flow (or ion flux vortex) near the electrode surface, driving these instabilities, has remained elusive due to limitations in conventional techniques such as scanning electron and atomic force microscopies, which are invasive and incapable of...

The recently proposed "900-day rule" in mouse aging studies-requiring lifespan extension over ultra-long-lived controls-aims to identify interventions that modulate intrinsic aging. While this standard raises scientific rigor, it may reduce relevance to how most organisms, including humans, actually age. In reality, aging unfolds under metabolically and immunologically stressful conditions-not in sterile, genetically uniform environments. Most people experience chronic inflammation, metabolic...

Africa stands at a decisive moment in which urgent action is essential to safeguard its brain health and economic stability. While Africa's population remains predominantly young, it is expanding and aging rapidly. This demographic shift is projected to drive a sharp rise in neurodegenerative diseases, including Alzheimer's, with profound health and economic costs-but brain health research, policy, funding and care across the continent remain critically underdeveloped. In this Perspective, we...

CONCLUSION: The findings of this study highlight healthcare providers' perceived facilitators and barriers to the integration of NCD care into HIV care platforms. The insights gained from this study hold the potential to inform tailored interventions, policy decisions, and capacity-building initiatives aimed at fostering successful integration and improving overall health care delivery to meet the needs of OALWH in resource-constrained settings.

No abstract

TNF receptor-associated factor 3 (TRAF3) is a signaling adaptor protein that is ubiquitously expressed but has highly distinct cell type-specific functions. TRAF3 plays critical roles in restraint of B lymphocyte activation, differentiation, and homeostatic survival. Consistent with such roles, loss-of-function mutations in TRAF3 have long been found in various human B cell malignancies. Mice lacking TRAF3 specifically in B cells have autoimmune manifestations, lymphadenopathy, and increased...

The evolution of continents is shaped by the growth and destruction of long-lived cratons, which serve as their stable cores. Processes for craton destruction are controversial because most invoked mechanisms occur frequently throughout Earth history, making the preservation of cratons for billions of years problematic. Here, we address this issue by presenting a crustal-scale analytical signal-amplitude model obtained from high-resolution airborne and shipborne magnetic data across cratons...

The desire to increase life expectancy, coupled with the decline in biological functions that occurs as we age, represents one of the most significant challenges facing our society. Age-related declines in biological functions contribute to frailty and morbidity, demanding innovative strategies to promote healthy aging. The circadian clock, which controls daily physiological processes, is intricately linked to aging and overall health. Circadian disruptions can lead to metabolic dysfunction,...

Δ133p53α is a naturally occurring isoform of the tumor suppressor protein p53. Δ133p53α functions as a physiological dominant-negative inhibitor of the full-length p53 protein (commonly referred to as p53). Δ133p53α preferentially inhibits p53-mediated cellular senescence, while it does not inhibit, or may even promote, p53-mediated DNA repair. Owing to this selective inhibitory activity that preserves genome stability, Δ133p53α represents a promising target for enhancement in the prevention and...

Mitochondrial dysfunction is a hallmark of aging and many age-related neurodegenerative diseases. Mild cognitive impairment (MCI) refers to a clinical condition characterized by noticeable cognitive decline that exceeds normal age-related changes but does not significantly interfere with daily functioning. MCI is often considered an early stage of neurodegenerative conditions, including Alzheimer's disease. We therefore investigated the relationship between mitochondrial function in peripheral...

CONCLUSIONS: The signatures verified through comprehensive functional genomics and genetic analyses may provide new targets for modulating the aging process and enhancing the quality of cell therapy products.

Tauopathies are neurodegenerative disorders characterized by the abnormal accumulation and aggregation of hyperphosphorylated tau protein. They can be primary or secondary depending on whether tau inclusions are the predominant pathology (e.g.: frontotemporal dementia related to tau) or are found with other proteinopathies (e.g.: Alzheimer's disease), respectively. Currently, there are no effective treatments to prevent or slow down progressive tau accumulation. Animal models play a critical...

CONCLUSION: A region-informed One-GMM method significantly improved CP segmentation accuracy over FS, providing a practical and accessible tool for CP quantification in AD and other research studies. Within this small cohort, no diagnostic group difference in CP volume was observed. An aging effect of CP volume was found within the CN group.

INTRODUCTION: A major contributor to age-related hearing loss is the decline of GABAergic inhibition, particularly in the inferior colliculus (IC), which is the midbrain hub of the central auditory system. The initial loss of inhibition is thought to be a compensatory mechanism in response to decreased peripheral excitation. However, the downregulation of inhibition in the IC persists with age and leads to functional disruptions and central neural gain. Neuropeptide Y (NPY) is co-expressed by a...