Aging & Longevity

To maintain protein homeostasis, which is essential for health, animals have developed complex protective mechanisms against various acute and chronic stresses. However, the coordination of responses to these protein stresses, especially their age-dependent changes, is not well understood. HSF-1 is a key regulator of protein homeostasis. Our study identifies PBS-7, a proteasome subunit, as its crucial regulator. In aged C. elegans, decreased PBS-7 binding reduces proteasome-mediated degradation...

CONCLUSION: Ubiquitination modification, autophagy process, cellular senescence and nervous system regulation may jointly contribute to the core molecular mechanism of ARHL. The hsa-miR-100-5p, hsa-miR-23b-3p, hsa-miR-373-3p, and hsa-miR-27b-3p may preliminarily act as key regulatory factors to participate in the pathophysiological process of ARHL, providing exploratory evidence for their potential application value as molecular markers.

Senescence is a tripartite cellular phenotype characterized by permanent growth arrest, resistance to apoptosis, and high secretory activity. Besides its physiological role in embryonic development and pathophysiological contribution to age-related tissue degeneration, in the context of tumor development senescence is an important suppressor mechanism, that counteracts accelerated proliferation. Among the many stressors that induce senescence is the external stimulation by cytokines. Although...

Aging is characterized by a progressive decline in physiological resilience and functional capacity, often accompanied by chronic, low-grade systemic inflammation, a phenomenon termed "inflammaging". This persistent inflammatory milieu contributes significantly to musculoskeletal degeneration, impaired neuromotor coordination, and reduced mobility, collectively diminishing quality of life, particularly among older adults. Key biological drivers of inflammaging include cellular senescence, immune...

During aging, stem cell persistence is favored over functionality, resulting in delayed responses to injury.

The genetic contribution to human longevity is greater than previously thought.

How heritable is human life span? If genetic heritability is high, longevity genes can reveal aging mechanisms and inform medicine and public health. However, current estimates of heritability are low-twin studies show heritability of only 20 to 25%, and recent large pedigree studies suggest it is as low as 6%. Here we show that these estimates are confounded by extrinsic mortality-deaths caused by extrinsic factors such as accidents or infections. We use mathematical modeling and analyses of...

DNA-protein cross-links (DPCs) are highly toxic DNA lesions that block replication and transcription, but their impact on organismal physiology is unclear. We identified a role for the metalloprotease SPRTN in preventing DPC-driven immunity and its pathological consequences. Loss of SPRTN activity during replication and mitosis lead to unresolved DNA damage, chromosome segregation errors, micronuclei formation, and cytosolic DNA release that activates the cyclic GMP-AMP synthase...

Plants display a wide range of life spans and aging rates. Although dynamic changes to DNA methylation are a hallmark of aging in mammals, it is unclear whether similar molecular signatures reflect rates of aging and organism life span in plants. In this work, we show that the short-lived model plant Arabidopsis thaliana exhibits a loss of epigenetic integrity during aging, which causes DNA methylation decay and the expression of transposable elements. We show that the rate of epigenetic aging...

Aging is characterized by a decline in the ability of tissue repair and regeneration after injury. In skeletal muscle, this decline is largely driven by impaired function of muscle stem cells (MuSCs) to efficiently contribute to muscle regeneration. We uncovered a cause of this aging-associated dysfunction: a cellular survivorship bias that prioritizes stem cell persistence at the expense of functionality. With age, MuSCs increased expression of a tumor suppressor, N-myc down-regulated gene 1...

The co-evolution of mitochondria and the nucleus established constant mito-nuclear communication that is essential for both cellular and organismal homeostasis. At the cell-autonomous level, mitochondrial perturbations activate retrograde pathways such as the mitochondrial unfolded protein response (UPR^(mt)) and the mitochondrial integrated stress response (ISR^(mt)), which couple organelle dysfunction to nuclear transcriptional programs, thereby promoting mitochondrial function and preserving...

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Cellular senescence contributes to aging and disease, and senolytic drugs that selectively eliminate senescent cells hold therapeutic promise. Although over 20 candidates have been reported, their relative efficacies remain unclear. Here we systematically compared 21 senolytic agents using a senolytic specificity index, identifying the Bcl-2 inhibitor ABT263 and the BET inhibitor ARV825 as most effective senolytics across fibroblast and epithelial senescence models. However, even upon extended...

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Leaf longevity is a fundamental plant trait that largely explains ecosystem functional dynamics in global pantropical moist forests. However, the signs, magnitudes, and mechanisms of the spatiotemporal variations in leaf longevity with ongoing climate change are still lacking. Using both ground measurements and gridded leaf age-dependent leaf area index data, we map the continental-scale variability of annual mean leaf longevity across pantropical moist forests over 2001-2023. We find a...

Human social connections are complex ecosystems formed of structural, functional and quality components. Weak social connections are associated with adverse age-related health outcomes, but we know little about the ageing-related processes underlying this. Using data from 7047 adults aged 50+ in the English Longitudinal Study of Ageing, we explore associations between diverse aspects of social connections and both older subjective age and accelerated physiological age using a validated...

CONCLUSIONS: The OAC-D identified five unique domains of depression, only one of which overlapped with DSM criteria. It demonstrated robust psychometric properties, providing a nuanced alternative to DSM-based measures and addressing the distinctive psychological challenges of cancer and aging.

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The potential of proteomic aging clocks for obesity research, and the extent of nonlinearity in longitudinal associations between body weight and biological aging, remain underexplored. We investigated how BMI at ages 18 and ~60, as well as changes in BMI from age 18 to ~60, relate to downstream epigenetic and proteomic aging. We also examined nonlinearity and interactions in these associations. Analyses were conducted in 401 Finnish twins with up to nine self-reported or measured BMI values...

CONCLUSION: These findings place mitochondrial proteome collapse at the center of aging and AD-seeded pathology, distinguish Aβ- and Tau-driven proteotoxic routes, and nominate a conserved panel of aggregation-prone proteins as mechanistic drivers and candidate biomarkers for early detection and intervention in AD.