npj aging最新文献

This study investigated how the timing and duration of 30% caloric restriction (CR) affect ovarian aging in mice. Mice were assigned to one of four groups: ad libitum (AL) control, long-term CR (3-11 months; CR/CR), early short-term CR (3-7 months; CR/AL), and late short-term CR (7-11 months; AL/CR). Long-term CR reduced body mass, improved insulin sensitivity, preserved the ovarian primordial follicle reserve, and attenuated ovarian macrophage infiltration compared to AL-fed mice. Metabolic benefits from CR were quickly reversed upon returning to AL feeding. Short-term CR, whether initiated early or late, did not preserve the ovarian reserve. Some benefits were observed with an early start CR, including reduced ovarian collagen deposition at 7 months and reduced macrophage infiltration at 11 months. Our findings indicate that only long-term CR preserves the ovarian reserve. Short-term CR positive effects on other ovarian aging hallmarks depended on an early age of onset.

The biological aging acceleration predicts both morbidity and mortality, while few investigations have examined its utility in evaluating transitions, e.g. development patterns, of atrial fibrillation (AF) and dementia. We aimed to investigate the utility of biological aging acceleration in predicting transitions of AF and dementia. A total of 402,955 participants (mean [SD] age: 56.5 [8.1] years; men: 45.9%) in the UK Biobank were included. Biological age was calculated using the phenotypic age, based on the chronological age and 9 biomarkers. A multi-state survival analysis was conducted to examine transition patterns between AF and dementia. The increased biological aging acceleration was consistently associated with all transition patterns between AF and dementia, including transitions from incident AF or dementia to the comorbidity. Strong linear associations were observed. Our findings highlight the overlooked utility of biological aging acceleration in evaluating the transitions of AF and dementia in the general population.

Thyroid cancer (THCA) shows rising incidence and aggressiveness in young-onset cases. Through integrated single-cell, transcriptomic, and proteomic analyses, we identified age-specific tumor-associated macrophage (TAM) genes, including OLR1 and SIGLEC1, linked to metastasis and immune dysfunction. These TAM biomarkers were validated at the protein level, highlighting their prognostic and therapeutic potential. Our findings reveal key TAM-driven mechanisms in young-onset THCA progression, warranting further clinical investigation.

Before human genome sequencing, a genome-wide study of sibling centenarian pairs identified a longevity-associated locus on chromosome 4. Here, we mapped the genes in this locus and identified a collagen gene, COL25A1. Introducing an SNP linked to longevity that changes a serine predicted to be phosphorylated to leucine in COL25A1, into col-99, the C. elegans ortholog, extended lifespan. These col-99(gk694263[S106L]) SNP-mutants exhibited enhanced innate immune-related transcriptional responses, and their lifespan extension was abolished by inhibiting the p38 MAPK pathway. YAP-1, a transcriptional co-activator responsive to extracellular matrix changes, was essential for this longevity. Mechanistically, we find that this SNP modifies furin-mediated cleavage of this transmembrane collagen in vitro, and expressing the cleaved extracellular domain of COL-99 alone was sufficient to prolong C. elegans' lifespan. These findings reveal a potential mechanism by which a human centenarian-associated SNP in COL25A1 influences furin cleavage and shedding of the collagen ectodomain to promote healthy longevity.

Kininogen-1 (KNG1) is an important pro-inflammatory and pro-oxidant factor, but its precise role in skin aging remains inadequately elucidated. Quantitative 4D proteomic-sequencing analysis identified upregulated KNG1 in 3- and 15-month-old C57BL/6J mouse skin, with immunohistochemical staining corroborating its increase in intrinsic aging. KNG1 overexpression in murine skin reduced dermal thickness, collagen fibre content, elastic fibre density, aging marker Lamin B1, and increased oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), while KNG1 knockdown ameliorated these aging-associated phenotypes. Protein-protein interaction analysis revealed the underlying mechanisms. KNG1 regulates elastic fibre degradation through membrane metallo-endopeptidase (MME) activity, modulates collagen fibre degradation via matrix metallopeptidase 1 (MMP1) and matrix metallopeptidase 9 (MMP9), and elevates oxidative stress through epoxide hydrolase 2 (EPHX2). Thus, KNG1 may serve as an intrinsic skin aging biomarker, promoting collagen fibre degradation through MMP1/MMP9, elastic fibre breakdown through MME, and oxidative stress through EPHX2. KNG1 downregulation may represent a prospective anti-aging target.

Despite suppressive anti-retroviral therapy (ART), some older people with HIV show adverse ageing phenotypes, and the underlying mechanisms remain incompletely understood. We recruited 30 men with HIV aged ≥ 50 years and 15 well-matched men without HIV and performed histological analyses on skeletal muscle biopsies and plasma biomarker measurement, in combination with clinical and functional assessments. Men with HIV showed higher frequencies of frailty, pre-frailty, sarcopenia, and pre-sarcopenia when compared to men without HIV. When assessing skeletal muscle, men with HIV had decreased mitochondrial complex I and IV protein abundance and myofibre regeneration, whilst fibrosis was increased, and plasma TNFα and MCP-4 levels were elevated. Spearman correlation analyses suggested that inflammation and mitochondrial respiratory chain deficiency may result in a damage response in skeletal muscle with resolution by fibrosis rather than regeneration. These findings thus provide plausible rationales for adverse ageing phenotypes in older men with HIV, including frailty and sarcopenia.

Osteoporosis, primarily characterized by low bone mineral density (LBMD), is a major skeletal disorder among postmenopausal women (PMW), yet its global burden remains poorly quantified. Leveraging data from the Global Burden of Disease (GBD) Study 2021, we assessed the LBMD burden in PMW across 204 countries and territories between 1990 and 2021. Metrics included deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs), with temporal trends evaluated via estimated annual percentage change (EAPC). We found that in 2021, LBMD was responsible for 219,552 deaths and 7.76 million DALYs in PMW globally, with age-standardized DALY rates reaching 979.2 per 100,000 population. Compared to premenopausal women, PMW experienced a 15.17-fold higher mortality, a 5.84-fold higher burden in DALYs, and a 6.29-fold higher burden in YLDs. While age-standardized rates (ASR) for deaths and DALYs showed slight declines from 1990 to 2021, the absolute number of LBMD-related deaths more than doubled, increasing from 91,941 in 1990 to 219,552 in 2021, largely driven by global population aging. South Asia experienced the greatest burden, with India reporting the highest DALYs rates. The burden was highest in women aged ≥80 years and increased most rapidly in those aged ≥95. Regions with a high Socio-demographic Index (SDI) exhibited lower mortality rates but disproportionately higher levels of disability, whereas low-SDI regions bore a greater burden of mortality. Projections to 2045 suggest a sustained rise in deaths and disability, despite modest rate reductions. These findings underscore the urgent need for age-tailored, equity-focused interventions to mitigate fracture risk and improve musculoskeletal health among aging female populations worldwide.

Early detection of Alzheimer's disease remains complex and costly despite advancements in neurobiological markers. We propose an innovative approach based on the topological and kinetic analysis of verbal exchanges to distinguish patients from healthy individuals. Without requiring full transcription, we leverage a convolutional network capable of identifying discursive patterns indicative of cognitive impairments. Our experiments, conducted with 80 participants, demonstrate performance levels exceeding 95% in cross-validation, comparable to computational approaches relying on biological markers. This robust and minimally invasive methodology could be easily integrated into clinical protocols, enhancing current diagnostics. It also holds the promise of cost-effectively extending monitoring to other neurodegenerative or psychiatric diseases.

Lifespan extension has not prevented age-related decline. We propose that diet acts as a molecular modulator of aging, influencing inflammation, the microbiome, and systemic resilience. Biological age markers and AI-powered multi-omics reveal actionable dietary targets, including food-derived signals and Nutrition Dark Matter. We highlight precision nutrition and the EIT Food Healthy Aging Think & Do Tank as pathways to align science, policy, and practice for healthy aging.

The relationship between epigenetic age acceleration (EAA) and midlife cognitive function remains unclear, with limited causal evidence. We investigated this association in 1252 Black and White middle-aged adults from the Bogalusa Heart Study (BHS) and conducted a two-sample Mendelian randomization (MR) analysis using GWAS summary statistics for EAA (N = 34,710) and cognition (N ≤ 106,162). In BHS, higher Hannum age acceleration, PhenoAge acceleration, and GrimAge acceleration (GrimAA) were each associated with slower processing speed (p < 0.05). Additionally, GrimAA was linked to lower global cognition scores (p < 0.001), independent of covariates. MR analysis suggested a potential link, showing that genetically predicted GrimAA was nominally associated with slower processing speed (p = 0.05). These findings suggest that epigenetic aging, particularly GrimAA, is independently associated with lower cognitive function in midlife and may play an important role in cognitive impairment, especially in processing speed.