Aging & Longevity

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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Somatic mosaicism originates from postzygotic errors and creates a unique genomic landscape in every cell and individual. The health impacts of somatic mutations range from neutral to severe, responsible for most cancers and contributing to neurodevelopmental, neurodegenerative and other multifactorial diseases. The molecular mechanisms driving this variability are diverse, dominated by replication errors of DNA polymerase ε in CpG contexts and by spontaneous cytosine deamination followed by...

Sarcopenia is characterized by the progressive loss of skeletal muscle mass and strength, accompanied by impaired regenerative capacity. This study examined age-related changes in skeletal muscle regeneration and the associated expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and myogenin (MyoG). Male C57BL/6 mice aged 3, 13, and 23 months were subjected to barium chloride (BaCl(2))-induced tibialis anterior muscle injury. In parallel, C2C12 cells were exposed to...

Acute liver failure (ALF) is a life-threatening condition often leading to hepatic encephalopathy (HE), a neuropsychiatric disorder characterized by cognitive deficits and motor dysfunction due to elevated ammonia levels and neuroinflammation. This study investigates the therapeutic potential of resveratrol (RSV), a SIRT1 activator, in mitigating the cognitive and motor impairments associated with ALF-induced HE. SIRT1 is an NAD+-dependent class III histone deacetylase and mammalian ortholog of...

Aging is an inevitable physiological process characterized by progressive functional decline and degenerative alterations across organ systems. Metabolic disturbance, particularly the disruption of substance and energy metabolism, is increasingly recognized as a central hallmark of aging. Emerging evidence suggests that dysregulation of the urea cycle (UC) contributes to aging-related pathological processes, including cognitive impairment; however, its role in astrocyte-mediated brain aging...

CONCLUSIONS: In this nationally representative cohort, high psychological resilience measured before death was associated with lower symptom burden across multiple domains in the last year of life. Resilience assessment may help identify individuals at risk for distressing end-of-life experiences and inform interventions to bolster late-life resilience.