Aging & Longevity

CONCLUSIONS: This study highlights the complex web of interrelations linking dementia with social, behavioural, and health-related factors in later life. Rather than implying causal direction, these findings illustrate how multiple factors cluster and coexist within older adults' lives. These interconnections may inform the design of holistic strategies that integrate employment opportunities, physical activity promotion, social participation, sleep health, and cerebrovascular prevention into...

CONCLUSION: Cognitive decline over four years was associated with an increased risk of mortality among older women. Further studies should explore whether declines earlier in life or among men are also associated with an increased risk of mortality.

The gut microbiome may shape how diet influences cognitive aging, but population-based evidence remains limited. In 784 older adults living in rural China (70-98 years old) with fecal metagenomics and structured dietary assessment, a modified healthful plant-based diet index (mHPDI) is associated with distinct gut microbial structure and taxonomic shifts (15 species, 17 genera). Among participants with repeated cognitive measurements, higher mHPDI is associated with better global cognition, with...

Aging and biological sex are critical moderators of sleep quality, which contributes significantly to age-related cognitive decline and Alzheimer's disease (AD) risk. This study investigated how age and sex moderated the relationship between subjective sleep quality and resting-state functional connectivity (rsFC) within networks associated with hyperarousal and cognitive processing. Using an exploratory-confirmatory approach across two datasets (N = 95 and N = 1244), we examined connectivity of...

Aging is a major risk factor for numerous diseases, including degenerative and metabolic disorders. Cumulative mitochondrial damage, elevated reactive oxygen species (ROS), and impaired mitophagy are hallmarks of aging. In this study, we generated a Drosophila version of the mito-SRAI reporter to monitor mitophagy in vivo and demonstrated an age-dependent decline in muscle mitophagy, accompanied by the accumulation of insoluble proteins, increased ROS levels, and mitochondrial damage....

The neurotransmitter system (NTS) composed of neurotransmitter receptors and transporters is associated with a variety of diseases and disorders. The identification of disease-associated NTS features is important for understanding disease mechanisms and for prioritizing potential therapeutic targets. The differences in the composition of NTS in aging and different diseases are not well understood. Here, we show how to integrate multi-omics data at scale, including single-cell and spatial...

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Werner (WRN) is the only human RecQ helicase family member with DNA exonuclease activity. WRN promotes genome stability through its functions in DNA replication, repair and telomere maintenance, the deficiency of which presents clinically as Werner syndrome, causing premature aging and cancer predisposition. The main DNA double strand-break sensor Ku70/80 heterodimer (Ku) is a known partner of WRN, which stimulates its nuclease activity. However, the molecular basis of Ku-WRN interplay is...

As global aging intensifies, elucidating reproductive health's epigenetic aging associations is crucial. However, the impact of reproductive history on multi-generational DNA methylation (DNAm) clocks remains insufficiently characterized, representing a significant gap in understanding biological vs. chronological aging divergence. This study analyzed 1117 U.S. women aged 50 or older from NHANES 1999-2002 to examine associations between reproductive history and 12 DNA methylation (DNAm)...

As age is a significant risk factor for multiple neurodegenerative diseases, investigating normal brain aging may help identify molecular events contributing to increased disease risk over time. Single-nucleus RNA sequencing (snRNA-seq) enables analysis of gene expression changes within specific cell-types, offering insights into the molecular mechanisms underlying aging. However, most brain aging snRNA-seq datasets use age-matched controls from studies focused on pathology and sample cortical...

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Cellular senescence is a hallmark of age-related disorders, including cancer, in which senescence contributes to tumor progression and treatment resistance. Targeting senescent cells therapeutically requires noninvasive methods to longitudinally monitor senescence burden. Here, we present an injectable nanoprobe for noninvasive detection of therapy-induced senescence in lung cancer and pulmonary fibrosis via urine testing. Using human biopsy samples, clinical transcriptomic datasets and mouse...

Optimal sleep has a vital role in promoting healthy ageing and enhancing longevity. Here we propose Sleep Chart to assess the relationship between self-reported sleep duration and 23 biological ageing clocks derived from in vivo imaging¹, plasma proteomics² and metabolomics³. First, a systemic, U-shaped pattern emerges between sleep duration and biological age gaps across nine brain and body systems and three omics technologies. The sample-specific lowest biological age gaps are achieved between...

The human brain relies on a complex network of connections to function, with white matter acting as the primary communication highway between different brain regions^(1,2). Disruptions in these critical communication pathways are linked to several neurological, psychiatric and developmental disorders^(3,4). Although clinicians have long used standard growth charts to track physical development⁵, with more recent work translating these to whole-brain and grey matter measurements^(6-9), there has...

Genomic stability is critical for cellular function; however, in the central nervous system, highly metabolically active differentiated neurons are challenged to maintain their genome over the organismal lifespan without replication. DNA damage in neurons increases with chronological age and accelerates in neurodegenerative disorders, resulting in cellular and systemic dysregulation. Distinct DNA damage response strategies have evolved with a host of polymerases. The Y-family translesion...

Transition toward senescence is a cellular response to various forms of stress. This phenomenon is evolutionarily conserved across species, from insects to humans. Senescent cells (SCs) permanently withdraw from the cell cycle and undergo physiological changes, notably the acquisition of a robust secretory activity characterized by the release of numerous molecules, including cytokines, chemokines, and metalloproteinases. Through this program, termed Senescence-Associated Secretory Phenotype,...

Impaired immune clearance of senescent fibroblasts is a putative driver of pulmonary fibrosis. Exhausted natural killer (NK) cells have been implicated in this process, yet the underlying immune evasion mechanisms remain poorly understood. Using single-cell RNA sequencing (scRNA-seq) and spectral flow cytometry, we identified natural killer group 2 member A (NKG2A) as the predominant inhibitory checkpoint receptor expressed on NK cells in fibrotic lung diseases. Mechanistic in vitro coculture...

Although mitochondrial function is essential for life in multicellular organisms, work from multiple model organisms has demonstrated that a mild impairment of mitochondrial function can increase lifespan. In C. elegans, a mutation in the isp-1 gene, which encodes the Rieske iron sulfur protein in Complex III of the mitochondrial electron transport chain, results in increased lifespan, enhanced resistance to stress and slow physiologic rates. While the molecular mechanisms involved are...

Advanced age is a well-known risk factor for severe complications in surgical patients with critical illnesses, partly due to declined intestinal mucosal defense, but the underlying mechanism remains largely unknown. Our study provided direct evidence from older human and mouse small intestines of the adverse impact of aging on Paneth cell functionality by impaired mitochondrial metabolism. Mechanistic investigation revealed a specific elevation of Paneth cell enriched microRNA-152 (miR-152) in...