Aging & Longevity

Blood inflammatory marker studies in aging and Alzheimer's disease (AD) research have faced numerous interpretative and methodological challenges that have hindered the field's understanding of the relationship between immune network regulation/dysregulation and aging health factors. We examined how blood inflammation markers directly relate to each other in typical aging, cognitively unimpaired adults using a conditional network analytic modeling approach. We further evaluated how blood...

Changes in peripheral CD8^(+) T cells are a hallmark of immune aging. However, the role of aged non-infiltrating CD8^(+) T cells in brain aging remains to be fully defined. Here, we showed that aged circulating CD8^(+) T cells and their secreted factors drove hippocampal-dependent cognitive decline. Using heterochronic parabiosis and transcriptomics analysis, we observed that peripheral CD8^(+) T cells maintained properties intrinsic to their age. Systemic exposure of young mice to aged CD8^(+)...

A critical challenge in sepsis treatment lies in its complex immune microenvironment, characterized by concurrent hyperinflammation and immunosuppression. This imbalance is jointly driven by dysregulated neutrophil programmed death and abnormal activation of the PD-1/PD-L1 immune checkpoint. Therefore, precisely modulating neutrophil fate and blocking this immune checkpoint are highly promising therapeutic strategies. We engineered an artificial exosome nano-decoy (AT@NV-PD1) that homes to...

Ageing is an inevitable, yet highly heterogeneous process shaped by genetic, epigenetic, and environmental influences. While most individuals experience progressive functional decline, a minority exhibits accelerated degeneration due to rare pathogenic mutations, whereas others achieve exceptional healthy longevity. This continuum-from progeroid syndromes to centenarians-provides a unique framework to examine how deleterious and protective genetic variants differentially modulate conserved...

The Hallmarks of Aging framework has become a widely accepted schema within geroscience, organizing diverse mechanisms of cellular and molecular decline. This article examines whether the Hallmarks function as a scientific paradigm and, beyond that, whether they have enabled genuine scientific progress-an angle largely absents from current literature. Drawing on models from the philosophy of science, the article evaluates the framework's status and impact from multiple perspectives. From Kuhn,...

CONCLUSIONS AND IMPLICATIONS: Participation in community gatherings is associated with reduced LTC costs among older adults with mild disabilities under the LTCI system. These programs may promote more efficient use of care resources and support municipal strategies to contain LTC costs.

CONCLUSIONS AND IMPLICATIONS: Home care and dementia were the primary drivers of nursing home entry in Sweden between 2020 and 2022, while social factors played a smaller role. Further investigations should ensure that those with dementia who are living alone or have multimorbidity are receiving adequate care. With continued population aging, it is essential that we monitor and adapt our policies and systems to ensure needs dictate access to care.

Mutations accumulate with age in most human tissues. While some undergo clonal expansion and contribute to disease, the mutational burden tolerated by a normal cell without functional decline remains unknown. Here, we repeatedly treat proliferating human primary fibroblasts with the point mutagen N-ethyl-N-nitrosourea, and analyze mutation burden by single-cell whole-genome sequencing. Mutation burden increases linearly to ~56,000 single-nucleotide variants per cell, with only a modest reduction...

Dielectric elastomers are soft electroactive polymers capable of large-strain actuation with the moniker artificial muscle. However, current dielectric elastomers exhibit limited operational stability when operated at strain and energy density in the neighborhood of natural muscles, due to mechanical fatigue or electrical breakdown. In this work, we design a dielectric elastomer comprising a bimodal network structure and zwitterionic side groups to overcome electro-mechanical instability and...

Age-related decline of the neuromuscular junction (NMJ), the peripheral synapse that controls muscle contraction, contributes to muscle weakness and impaired motor function in aging. The NMJ comprises a motor axon terminal, a skeletal muscle fibre, and terminal Schwann cells (tSC). Neurotrophin signalling is essential for mature NMJ organisation, with the p75 receptor acting as a key regulator of its morphology and function. However, the potential contribution of p75 to age-related NMJ decline...

Vaginal aging is a multifactorial biological process characterized by structural, functional, and molecular alterations driven primarily by estrogen decline. This review summarizes current evidence on potential biomarkers across five domains: physiological parameters, imaging features, histological changes, and molecular alterations. We further discuss methodological challenges and future research directions necessary to establish standardized and clinically applicable biomarkers. Understanding...

Clove (Syzygium aromaticum) extracts promote longevity in several model systems, yet the underlying molecular mechanisms responsible for the pro-longevity remain poorly defined. This study utilized a Saccharomyces cerevisiae model to investigate how clove extracts modulate two primary hallmarks of cellular aging: oxidative damage and the decline of protein quality control systems. Clove extracts promoted increased chronological lifespan (CLS) of yeast cells. The change in longevity was...

Aging is accompanied by a progressive decline in intestinal barrier integrity, resulting in increased permeability to luminal microbes and microbial products and contributing to chronic low-grade inflammation ("inflammaging"). While epithelial and microbial changes have been extensively studied, the role of intestinal T cells as active regulators of barrier homeostasis during aging remains underappreciated. The gut harbors the largest population of T cells in the body, including diverse...

CONCLUSIONS: Loneliness emerged as the factor most consistently associated with emotional distress in older adults. These findings underscore the importance of designing public policies and psychosocial interventions focused on reducing unwanted loneliness and strengthening social connectedness in both institutional and community settings.

CONCLUSIONS: Self-reported driving concerns demonstrate predictive validity for future crashes, but a substantial minority of crash-involved drivers remain undetected by self-report. Education and TMT-B performance may serve as clinically actionable markers for identifying these "silent" at-risk drivers.

The global increase in neurodegenerative disorders such as Alzheimer's disease has prompted the search for effective non-pharmacological interventions. Chrono-exercise which is the physical training aligned with circadian rhythms has emerged as a novel strategy to strengthen cognitive resilience. This study explores the impact of chrono-exercises, incorporating aerobic, resistance, and combined modalities, performed at the early dark (ZT13) and early light (ZT1) phases in an aluminum chloride...

Depression and Alzheimer's Disease (AD) are both diagnosed in women twice as often as in men. Moreover, a history of untreated depression confers a 2-to-5-fold increase in the risk of developing dementia. Finally, biological factors such as sex differences in immune response increase rates of depressive pathology among women. Importantly, the prevalence of mid-to-late-life depression (MLD) worldwide and its misdiagnosis due to clinical overlap with AD hinder accurate assessment and timely...

Despite extensive research, molecular differences in human populations and the influence of ancestry, age, geography, and diet are poorly understood. We performed comprehensive multiomics profiling (including genomics, transcriptomics, proteomics, metabolomics, lipidomics, metallomics, glycomics, and microbiomics) on samples from 322 healthy individuals of European, East Asian, and South Asian ancestry across multiple continents. We identified ethnicity-associated molecular features linked to...

Lipid droplets (LDs) are lipid-storage organelles that have gained interest in neurodegenerative diseases, yet their physiological role in the brain is not fully understood. Classical LD detection using lipophilic dyes like BODIPY 493/503 (BD493) or antibodies against LD coat proteins typically reveals few LDs in healthy brain tissue. In contrast, our recently developed endogenous LD-reporter mouse showed numerous LDs in the developing and adult brain without staining. To understand this...

Cellular senescence is increasingly recognized as a fundamental driver of cardiovascular ageing; however, its molecular heterogeneity, cell-type specificity, and translational relevance remain incompletely understood. Accumulating evidence indicates that cardiovascular senescence is not a uniform or cell-autonomous process, but rather an emergent property of interacting endothelial, vascular smooth muscle, immune, and stromal cell networks shaped by metabolic stress, immune dysregulation, and...