Aging & Longevity

Macroautophagy/autophagy is a well-established homeostatic mechanism that contributes to the integrity of multiple regulatory biological activities including but not limited to the gastro-intestinal tract and cognitive integrity. Autophagy also plays a central role in tissue regeneration, metamorphosis and development whereas defects in autophagy are associated with a wide range of disorders including metabolic diseases such as diabetes, organ pathophysiologies including liver, lung and heart...

Age-related endothelial dysfunction in the cerebral microcirculation contributes significantly to the pathogenesis of vascular cognitive impairment and dementia (VCID). Time-restricted eating (TRE) has emerged as a promising lifestyle intervention with beneficial effects on metabolic and vascular health; however, the mechanisms by which TRE influences the brain microvasculature remain incompletely understood. In particular, the role of circulating factors induced by TRE in modulating endothelial...

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Tendinopathy is a common condition that causes long-term pain. The inflammatory microenvironment (inflamed soil) promotes the ingrowth of sensory nerves (a key pain trigger) and induces functional impairments in tendon stem/progenitor cells (TSPCs) (dysfunctional seeds). These interconnected processes collectively drive the progression of tendinopathy, which is frequently accompanied by persistent pain. Here, we develop a multifunctional nanoplatform (MSM-DTM) by integrating macrophage-sensory...

Skeletal muscle aging is a complex biological process that involves coordinated changes in multiple cell types. Recent breakthroughs in single-cell sequencing technology have provided new perspectives regarding this process. Here, we systematically summarize current progress in single-cell technology with respect to skeletal muscle aging. We focused on specific molecular characteristics and interaction networks of muscle fiber, satellite and immune cells during aging. Aging skeletal muscles...

Tumor senescence is a durable cell-cycle arrest triggered by oncogenic signalling, DNA damage and therapeutic stress. Although senescence can restrain malignant expansion, heterogeneous senescence-associated secretory programs can also promote tumor progression, immune evasion and treatment resistance. Crucially, the composition, magnitude and persistence of these secretory programs vary across cell types, microenvironmental niches and treatment phases, making binary detection of "senescent...

The nucleus is a highly organized and dynamic organelle, with hierarchical layers ranging from nucleosome positioning to chromatin domains and higher-order 3D genome topology. Viewed over time as the 4D nucleome, this organization enables precise and context-dependent transcriptional control. In the heart, dynamic nuclear architecture orchestrates precise transcriptional programmes that control lineage commitment and the establishment of cardiac cell types crucial not only for heart development,...

In senescent cells, functional alterations in organelles like mitochondria and lysosomes are well characterized, but senescence-associated changes in Golgi function are not. An RNA interference screen revealed that silencing subunits of the coatomer protein I (COPI) complex, critical for intracellular transport involving the Golgi, reduced extracellular vesicle uptake. In proliferating WI-38 fibroblasts, silencing COPI constituents COPA, COPB1, COPB2, or COPD induced ATF4 production and...

Changes in gene expression have been observed in the aging human brain, but our understanding of the underlying regulatory mechanisms remains limited. To unravel these complexities, we analyzed single-nucleus gene expression, chromatin accessibility, DNA methylation, and three-dimensional (3D) chromatin architecture from human hippocampal tissues spanning the adult lifespan. We identified both linear and nonlinear dynamic gene regulatory programs during aging. Between the ages of 50 to 75,...

Aging tissues gradually lose cellular diversity due to stem cell exhaustion. A new PLOS Biology study utilizes advanced lineage tracing to track intestinal stem cell lineages across the life span. The findings reveal clonal attrition happens in early ages.

CONCLUSION: Older adults with intact tactile sensation showed stronger hand dexterity-cognitive associations, highlighting sensorimotor integrity as relevant for early screening and functional evaluation. Stratified patterns suggest possible cognitive group differences that merit further study.

Cellular senescence is a context-dependent cellular state characterised by persistent cell-cycle arrest, epigenetic remodelling, metabolic reprogramming and acquisition of a senescence-associated secretory phenotype. Transient senescence contributes to embryogenesis, tissue repair and tumour suppression, whereas persistent senescent cell populations accumulate with advancing age across multiple tissues, in part owing to declining immune-mediated clearance and intrinsic resistance to apoptosis,...

Global population ageing is increasing the burden of chronic disease, functional decline, and loss of independence. For most organs, decline in function starts during the 5th decade of life. Micronutrient (MN) insufficiencies/deficiencies are common and may accelerate biological ageing. MNs are required to support multiple physiologic processes, including mitochondrial homeostasis. Age-related declines in organ function are tightly linked to mitochondrial dysfunction, oxidative stress,...

Heterochronic parabiosis improves physiological and cognitive function in aging rodents; these benefits appear to be derived from the removal of aged blood plasma components and the addition of younger ones. In humans, removing plasma from older individuals with Alzheimer's disease (AD) and replacing it with saline and albumin delayed cognitive deterioration in a large clinical trial. However, mimicking heterochronic parabiosis in humans by removing large volumes of a patient's blood plasma and...

CONCLUSIONS: AGE-PAIRS demonstrates the feasibility of engaging physician alumni as mentors in early geriatrics education and suggests that structured intergenerational mentorship can support empathy and professional identity formation. Future work will integrate AGE-PAIRS more deeply into graded coursework, add structured mentor reflections, expand participation across all class years, and evaluate higher-level outcomes such as geriatrics knowledge, clinical performance, and interest in...

INTRODUCTION: Fidelity of detailed information retrieved from long-term memory (LTM) declines in aging due to changes affecting learning and remembering processes. Such behavioral deficits correspond with functional alterations in the hippocampal formation. However, it is unclear whether age-related decline in high-fidelity retrieval alters functional connections between hippocampal and cortical regions.

CONCLUSIONS AND IMPLICATIONS: Among community-dwelling older adults, MRI-derived muscle quality deteriorated substantially faster than muscle quantity over 4 years and more closely paralleled declines in physical performance. These findings suggest that age-related muscle deterioration is driven primarily by qualitative degeneration rather than simple loss of muscle mass and support the use of imaging-based muscle quality measures as sensitive biomarkers of biological muscle aging.

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CONCLUSION: HBDL-based free-weight resistance training is a safe, feasible, and effective strategy to improve body composition, trunk extensor function, and mobility in older women.

Homotypic targeting is the inherent ability of cells to preferentially interact with cells of the same type, a phenomenon seen in cell adhesion, tissue formation and immune responses. However, its potential remains underexploited. Here we report a strategy to substantially enhance homotypic targeting through extracellular vesicles secreted by cells. By engineering the surface of small extracellular vesicles (sEVs) with lanthanides, we amplify specific cell-sEV interactions by more than 25-fold,...