Aging & Longevity

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...

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...

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...

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...

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...

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...

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...

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...

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...

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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...

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...

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...

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...

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.

Chronic intermittent hypoxia (CIH), a cardinal pathophysiological feature of obstructive sleep apnea (OSA), repeatedly exposes the heart to hypoxia-reoxygenation stress. The cardiac outcome of CIH, however, may depend on the biological state of the target myocardium. Here, we investigated whether a pre-existing aging-related myocardial susceptibility lowers the tolerance threshold for CIH-induced injury and whether Dynamin-related protein 1 (Drp1) contributes to the enhanced vulnerability of...

INTRODUCTION: The ability to perceive spatial changes is crucial for everyday life. However, the effects of age on multisensory integration in spatial change detection are still less researched. Here, we investigated whether audio-visual stimulation enhances spatial change detection compared to auditory-only processing, and whether older adults benefit more from multisensory stimulation than younger adults.

Stem cell-based therapies show promise for tissue regeneration but are limited by therapeutic instability, particularly in aged tissues. Here, multi-omics profiling of regenerating bone reveals marked depletion of S-adenosylmethionine (SAM), indicating epigenetic dysregulation associated with impaired repair. To address this, we develop a spatially compartmentalized, fusogenic nanovesicle system (SMNV), termed a "nanoconcentrisome," composed of SAM-loaded fusogenic liposomes encapsulating...

Aging is a complex biological process governed by conserved genetic and metabolic pathways. Increasing evidence has identified the gut microbiota as a critical modulator of host aging and healthspan. The Caenorhabditis elegans model provides a powerful system to elucidate the molecular determinants of this cross-kingdom dialogue. Recent advances in this model organism reveal that gut microbes may regulate aging through two distinct yet convergent mechanisms: (i) the production of small-molecule...

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