Aging & Longevity
Computational precision nutrition for sarcopenia and associated multimorbidity in ageing
Sarcopenia is the age-related progressive decline in both skeletal muscle mass and function. It acts as an exacerbator of multimorbidity, engaging in bidirectional pathological cycles with multiple chronic diseases, and contributes substantially to increased mortality, disability and healthcare costs. Current nutritional support is often limited by a generic one-size-fits-all approach that fails to account for substantial inter-individual variation across genetics, metabolism, lifestyle, gut...
Deep learning-derived magnetic resonance imaging masseter muscle volume is associated with oral impairment and cognitive frailty in older Japanese adults
CONCLUSIONS: CNN-derived masseter muscle parameters from magnetic resonance imaging were inversely correlated with oral impairment in older adults. This approach enables scalable and objective oral phenotyping from imaging data and highlights its potential application in large-scale epidemiological studies of aging and functional decline.
A multi-scale framework to advance experimental models of skin aging
Skin aging is a multifactorial, multiscale process driven by the interplay between intrinsic cellular decline and extrinsic environmental exposures. Increasing evidence positions the skin as a dynamic interface and sensitive "window" reflecting systemic aging. However, research remains fragmented across scales, and existing models fail to capture the full complexity of systemic regulation. In this review, we introduce a hierarchical four-dimension framework of skin aging to systematically...
High-intensity interval training preferentially improves cardiac function via enhanced histone lactylation and macrophage polarization in SAMP8 mice
Aging is associated with progressive cardiac dysfunction, characterized by increased myocardial fibrosis, chronic inflammation, and impaired myocardial structure. Exercise is a well-established, cost-effective intervention for age-related cardiovascular decline, yet the underlying epigenetic mechanisms remain to be fully elucidated. Recent studies have implicated histone lactylation as a regulatory mark that modulates macrophage polarization and inflammatory responses. Histone lactylation, a...
Construction and Validation of Plasma Protein-Based Musculoskeletal Biological Age and Genetic and Environmental Risk Profiles
The musculoskeletal system is key to aging. Nonetheless, existing protein-based musculoskeletal aging clocks have limited predictive performance and fail to characterize genetic or environmental determinants. We first constructed a musculoskeletal protein pool by integrating transcriptomic enrichment, protein functional annotation, and literature expertise. Two musculoskeletal aging clocks-MSKAge and MSKAgeMort-were then developed using proteomic data of 21,070 UK Biobank participants....
An aging essential 8: closing the gap between geroscience and the public it serves
Longevity science has advanced faster than the public's capacity to interpret it. Biological age tests, longevity clinics, and consumer wearables now reach millions of people, yet no shared framework exists to tell an individual what those numbers mean or what to do about them. Cardiovascular medicine encountered a comparable problem and resolved it not with a new therapeutic but with a communication instrument: Life's Essential 8, which distilled a contested risk landscape into eight components...
Linking modifiable risk factors to vascular and neurodegenerative brain changes
Dementia reflects vascular and neurodegenerative processes in late life, yet studies often examine risks and outcomes individually. This study tested whether the cumulative burden of risks relate to vascular brain injury and cognitive performance and whether brain markers are associated with part of these associations through cross-sectional indirect pathways. Cross-sectional data were drawn from 38,414 older adults in the National Alzheimer's Coordinating Center database. A composite index...
Aging limits neuronal regeneration from glia in the mouse retina
Reprogramming resident glia into neurons holds great therapeutic promise for neurodegenerative diseases across the central nervous system, yet these strategies have been developed largely in young animals. Because aging is the primary risk factor for neurodegeneration, whether glia-to-neuron reprogramming remains effective in aged tissue is a critical unanswered question. Here, using the retina as an accessible part of the central nervous system, we show that aging is a major barrier to...
Plasma engineered carbon molecular sieve membranes for precise and stable hydrogen permeation
Carbon molecular sieve (CMS) membranes represent a high-performance alternative to polymers, surpassing the trade-off limits between permeability and selectivity typically seen in conventional polymeric membranes. Their efficacy stems from a precise molecular sieving mechanism, enabling exceptional gas separation performance. However, a challenge persists in fine-tuning their microporous structure to achieve effective kinetic separation of gas molecule pairs with small differences in kinetic...
Development of mitochondrial mutator pigs exhibiting increased mitochondrial DNA mutations and premature aging via prime editing
The accumulation of mitochondrial DNA (mtDNA) mutations is a primary driver of mitochondrial dysfunction, which is intrinsically linked to aging and various pathologies. POLG, the catalytic subunit of DNA polymerase gamma, is essential for mtDNA replication; notably, a deficiency in its proofreading function precipitates the accumulation of mtDNA mutations. In this study, by combining prime editing with somatic cell nuclear transfer technology, we successfully generated a mitochondrial mutator...
Trajectory-based identification of cognitive-performance phenotypes across adulthood from psychophysiological testing
CONCLUSION: Elastic principal trees represent cognitive-performance profiles as connected branches and provide a graph-ordering coordinate unavailable from ordinary discrete clustering. The results are exploratory, cross-sectional, and non-diagnostic and should not be generalized to neurodegenerative aging without older, clinically characterized, longitudinal cohorts. Among the examined alternatives, the original full-feature six-PC solution was retained for interpretation because the...
Proteostasis breakdown and aggregate diversity in aging and neurodegenerative disease
Protein aggregation and proteostasis decline are central features of aging and neurodegenerative disease, arising from progressive impairment of protein quality-control systems and transitions into aggregation-prone states. During aging, diverse proteins, including metabolic and proteostasis-related factors, gradually accumulate in aggregated forms as proteostasis capacity declines. Although these aggregates often remain compatible with cellular function, increasing aggregate burden...
Sex-specific aging clocks from a large-scale human phenome reveal distinct aging transitions and circulating signatures
Aging is a primary risk factor for chronic diseases, yet its progression varies among individuals and between sexes. Here, under the X-Age Project, we profiled the clinical aging phenome of the Multicentric Chinese Aging Study (mCAS) through a cross-sectional analysis of 172 clinical measures from more than 100,000 participants aged 18-98 years across three centers. These profiles enabled sex-specific clinical aging clocks that revealed divergent aging trajectories between women and men during...
cGAS-deficient mice display premature aging associated with derepression of LINE1 elements and inflammation
Aging-associated inflammation is a driver of multiple age-associated diseases. Cyclic GMP-AMP synthase (cGAS) contributes to inflammaging by responding to endogenously-derived cytoplasmic DNA in aged cells. Although cGAS-knockout (KO) mice are viable, their aging has not been characterized. Unexpectedly, we found that cGAS KO mice exhibit an accelerated-aging phenotype, with induction of inflammation in multiple organs. cGAS KO mice display shortened median lifespan and increased frailty...
Longevity medicine cuts 'desire paths' in primary care
No abstract
A geroprotective probiotic and its functional metabolite counteract inflammaging to extend healthspan
The gut microbiome profoundly influences host aging, yet the specific microbes and mechanisms governing divergent aging trajectories remain elusive. In this study, we delineated enterotype-specific gut microbial remodeling during aging and developed a microbiome-based aging clock (MicroAge) to track biological aging trajectories. We identified Bifidobacterium pseudocatenulatum (B. pseudocatenulatum) as a candidate geroprotective species consistently depleted during aging across both sexes and...
Elevated contractility drives implantation failure in mouse embryos from aged females
Women in their mid-30s experience a marked decline in fertility. The origin of these fertility defects resides in the implantation capacity of the embryo itself, but the mechanistic basis of this impairment is not well understood. Here we identify a core mechanical defect in embryos from aged females that impairs their implantation competence. Using mouse models, we find that reproductive ageing drives excessive contractility in the trophectoderm, the outer epithelial lineage that enables...
Oligodendrocyte dysfunction in human age-related cognitive decline
Cognitive decline in aging impacts quality of life, for which therapeutic interventions are lacking. Why some individuals experience more severe cognitive decline with aging is unclear. Here we uncover a role for the brain's myelin-forming cells-oligodendrocytes-in explaining this variance. By investigating neuropathological and transcriptomic changes in human white matter associated with individual rates of cognitive decline in aging, we find that worse cognitive trajectories unexpectedly...
Partial reduction of the mitochondrial lipoyltransferase LipT2 promotes longevity and redox remodeling in Drosophila
Lipoic acid is an essential cofactor for mitochondrial multienzyme complexes, and mutations in the lipoyltransferase LIPT2 cause severe metabolic and neurological defects in humans. In Drosophila, two independent lipT2 loss-of-function alleles cause severe physiological abnormalities in homozygotes. Here, we show that heterozygotes for these same alleles exhibit significantly extended lifespan and delayed age-dependent decline in locomotor performance. Metabolic analysis revealed no major...
Unveiling intervention targets: urban-rural disparities in depression-anxiety symptoms networks among Chinese older adults living alone
CONCLUSIONS: Central and bridge symptoms may represent effective intervention targets for anxiety and depressive symptoms in older adults living alone. Clinical interventions should consider geographic disparities in symptom presentation.
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