Background Sleep has been proven to be associated with various chronic diseases and aging. However, many individuals fail to achieve recommended sleep durations on weekdays and opt for compensatory sl...

Mohri et al. show that, in response to genotoxic stress, melanocyte stem cells undergo senescence-associated differentiation, causing their depletion and protecting them against melanomagenesis. This process is suppressed by carcinogens.

The Human Cell Aging Transcriptome Atlas contains single cell RNA-sequencing data from 3,475 human samples and interactive tools to explore age-related alterations in gene expression and go term enrichment in a diverse set of tissues and cell types.

Xiong et al. integrated genetic analysis of multi-omics data with GWASs to construct a comprehensive molecular landscape of nine organ-specific aging clocks and four blood-based epigenetic clocks. Thi...

Aging, a complex biological process, entails sequential changes in organisms that elevate the risk of frailty, disease, and mortality, affecting individuals at the level of cellular, organ, and organism. This process is influenced by genetic diversity, socioeconomic status, healthcare infrastructure, lifestyle choices, and cultural practices. Gerontology delves into the factors shaping longevity, aging processes, and aging from both evolutionary and individual perspectives. Centenarians and supercentenarians serve as models for studying exceptional longevity, offering insights into the aging process and resistance to age-related diseases. This research investigates common genetic variations (SNPs) shared among 3 centenarians and 18 supercentenarians, individuals aged 110 years or older. 754,520 SNPs were found to be common among all the 21 samples. Utilizing SNPnexus, a genetic variant annotation tool, we annotated coding variants and assessed potential disease susceptibilities associated with these variants. Ensembl was used as an annotation system, we annotated 1,607,122 variants, and found 11,348 coding variants. Among them, 4980 had non-synonymous variants, and 110 variants were observed to have deleterious effects. These deleterious SNPs were linked with 79 genes among them 16 novel variants were identified in 9 genes. The population frequency comparison using the 1000 Genomes Project and gnomAD revealed that a subset of these common, non-synonymous SNPs and deleterious SNPs had minor allele frequencies (MAF) below 1% or were absent entirely, suggesting potential rare variants specific to this cohort. In addition, we also found statistically significant (p < 0.05) 148 enriched pathways, among them the top enriched pathways such as extracellular matrix (ECM) remodeling, signal transduction, disease-associated pathways, sensory processing and metabolism of proteins and RNA. These preliminary findings may help prioritize candidate variants and genes for future studies on larger cohorts with appropriate controls can help in understanding the genetic basis of exceptional longevity.

Background Aging is a complex biological process characterized by progressive molecular alterations across multiple organ systems, significantly influencing disease susceptibility and mortality. Unraveling molecular interactions driving aging is crucial for interventions promoting healthy aging and mitigating senescence. However, the systemic mechanisms governing both inter-organ interactions and organ-specific aging trajectories remain incompletely characterized. Methods To investigate the molecular dynamics of aging, we conducted a systematic multi-omics analysis of 400 tissue samples collected from 10 organs (brain, heart, intestine, kidney, liver, lung, muscle, skin, spleen, and stomach) in mice at four distinct life stages: 4, 8, 12, and 20 months (from youth to elderly). Proteomic profiling was performed using data-independent acquisition (DIA) technology, while metabolomic analysis was performed in both positive and negative ion modes. Differential expression analysis of proteins and metabolites was employed to construct a comprehensive multi-organ aging dataset. Results Proteomic profiling across ten organs at four age stages identified a total of 14,763 protein groups (PGs). Of these, 18 proteins, including Ighm, C4b, and Hpx, exhibited consistent age-related differential expression patterns across all ten organs. Functional enrichment analysis highlighted the humoral immune response as a primary driver of age-related expression changes. Additionally, this study mapped a set of age-unique proteins, such as Hp, Egf, and Arg, with distinct expression patterns in aging organs. Metabolic analysis identified 3779 metabolites, with key aging-related metabolites such as NAD+, inosine, xanthine, and hypoxanthine showing significant expression changes across multiple organs. Pathway enrichment analysis revealed consistent alterations in purine metabolism, pyrimidine metabolism, riboflavin metabolism, and nicotinate/nicotinamide metabolism during multi-organ aging. Conclusions This study provides a multi-omics atlas of multi-organ aging, revealing both intra- and inter-organ similarities and heterogeneities. These findings offer valuable insights into the molecular mechanisms underlying geriatric health decline and serve as a foundational resource for organism-systematic early warning and targeted interventions against aging-associated pathologies.

Researchers are testing multiple treatments for the rare genetic conditions

This Review discusses the effects of three age-associated stressors—loss of proteostasis, oxidative damage and dysregulated nutrient sensing—on global protein synthesis and highlights how altered translation is used by the cell as a stress sensor.

Aging, a universal biological process in complex organisms, is increasingly recognized to be driven by progressive loss of epigenetic information, as proposed in the Information Theory of Aging (ITOA)...

A DNA repair function in a cytosolic sensor demonstrates a potential role in naked mole-rat longevity

Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that na...

Li S, et al. J Vet Sci. 2025 Oct;26(S1):S5-S21. https://doi.org/10.4142/jvs.25181

We estimated 11 organ-specific proteomic aging using the elastic net regularization model. Our findings revealed that organ-specific proteomic aging is influenced by lifestyle factors and baseline he...

Marriage has been a hot topic since ancient times forever, yet there is little research evidence on marital status as an important socio-behavioral fa…

Cells can enter a stress response state termed cellular senescence that is involved in various diseases and aging. Detecting these cells is challenging due to the lack of universal biomarkers. This r...

Neurodegenerative diseases (NDDs) pose significant challenges in early detection and treatment due to their complex pathophysiology and heterogeneous clinical presentations. MicroRNAs (miRNAs), small noncoding RNAs that regulate gene expression, have emerged as promising diagnostic biomarkers and therapeutic targets in NDDs. Pathological examination of affected tissues reveals early synaptic dysfunction, protein misfolding, and neuroinflammation occur prior to overt clinical symptoms, highlighting the importance of sensitive diagnostics approaches in prodromal stages. This review summarizes for researchers on the role of miRNAs in NDDs by examining their diagnostic potential in biofluids such as blood and cerebrospinal fluid, and their therapeutic applicability through inhibition or replacement strategies. Literature from peer-reviewed databases was assessed with a focus on recent advances in molecular detection platforms, computational modeling of miRNA–mRNA interactions, and preclinical/clinical investigations.More than 2600 human miRNAs have been identified, collectively regulating over half of mammalian protein-coding genes. Quantitative methodologies, particularly reverse transcription quantitative PCR (RT-qPCR), enable reliable miRNA profiling, facilitating early diagnosis and prognosis of NDDs. Therapeutic strategies, including antagomirs, mimics, sponges and viral or non-viral delivery systems, show promise in modulating disease pathways. However, significant challenges remain, including variability in miRNA extraction and quantification protocols, off-target effects, delivery barriers across the blood brain barrier and limited reproducibility across studies. MiRNAs represent a class of molecular tools with potential to transform diagnostics and therapeutics in NDDs. Future research should prioritize methodological standardization, validation in large multicenter cohorts, and improved computational approaches to elucidate miRNA-mediated regulatory networks in NDDs. Replication studies and translational research are essential harnessing the the full clinical utility of miRNAs in the management of Alzheimer disease, Parkinson disease and other NDDs.

Background Accelerated aging is a dynamic process, yet few studies examined the association of changes in accelerated aging with cardiovascular disease (CVD) and mortality. This study aims to evaluate this association in three prospective cohorts from China and the UK. Methods Data were drawn from the Kailuan cohort (n = 107,830), the Dongfeng-Tongji (DFTJ) cohort (n = 14,032), and the UK Biobank (n = 316,087). Accelerated aging was assessed by PhenoAge and Klemera-Doubal method (KDM) age, measured at baseline (Kailuan cohort: 2006–2009; DFTJ cohort: 2008–2010; UK Biobank: 2006–2010) and the first follow-up (Kailuan cohort: 2010–2013; DFTJ cohort: 2013; UK Biobank: 2012–2013). Changes in accelerated aging were classified as persistent accelerated aging, recovery from accelerated aging, delayed accelerated aging, and stable non-accelerated aging. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Meta-analysis was performed to summarize estimates across three cohorts. Results Median follow-up periods were 10.3–15.9 years across three cohorts. When defining accelerated aging by PhenoAge, baseline accelerated aging was significantly associated with increased risks of CVD (pooled HR: 1.41, 95% CI: 1.25, 1.60) and mortality (pooled HR: 1.47, 95% CI: 1.33, 1.63). Compared to participants with persistent accelerated aging, participants recovering from accelerated aging (pooled HR of CVD: 0.76, 95% CI: 0.72, 0.81; pooled HR of mortality: 0.84, 95% CI: 0.78, 0.89), delaying accelerated aging (pooled HR of CVD: 0.75, 95% CI: 0.70, 0.79; pooled HR of mortality: 0.77, 95% CI: 0.72, 0.83) or maintaining non-accelerated aging (pooled HR of CVD: 0.59, 95% CI: 0.48, 0.71; pooled HR of mortality: 0.58, 95% CI: 0.55, 0.62) exhibited decreased risks of both CVD and mortality. When defining accelerated aging by KDM age, the results remained consistent with those of PhenoAge. Conclusions Accelerated aging is a significant risk factor for CVD and mortality. Recovering from or delaying accelerated aging, or maintaining non-accelerated aging, was associated with reduced risks of CVD and mortality. Graphical Abstract

Organelles spit out DNA contaminated with damaging components, leading to the activation of inflammatory enzymes, mouse experiments show.

The testis, with the highest number of transcriptionally active genes among human tissues, offers a unique window into how aging affects complex gene regulation. Recent advancements in single-cell RNA sequencing have enabled multi-species studies of aging-related transcriptome changes in testes. However, a comprehensive aging-related cross-species platform for analyzing testicular single-cell transcriptomes remains absent. To address this gap, we developed Aging-TCA (Aging-related Testicular Cell Atlas, available at http://tca.xielab.tech/)— a comprehensive online platform containing aging-related testicular single cell and spatial transcriptome profiles from human, cynomolgus monkey, mouse, and zebrafish across 89 samples and over 460, 000 testicular cells, nuclei or spots. Aging-TCA provides versatile tools for temporal and spatial analyzing testicular aging, including aging-related testicular gene expression visualization, cell-cell communication comparisons, cell-trajectory analysis, gene regulatory network analysis, testicular cell type auto-identification, time-series analysis, and spatial transcriptome comparisons. In summary, we provide a novel platform Aging-TCA for advancing cross-species research into testicular aging, facilitating future investigations in this field.

AbstractBackground. To estimate biological age, we developed a proteomic aging clock in cancer-free participants (CaPAC) and examined its association with

Aging | doi:10.18632/aging.206299. Francesco Neri, Shuyuan Zheng, Mark A. Watson, Pierre-Yves Desprez, Akos A. Gerencser, Judith Campisi, Denis Wirtz, Pei-Hsun Wu, Birgit Schilling

Cellular senescence has gradually been recognized as a key process, which not only inhibits the occurrence of early tumors but also promotes advanced malignant progression through secretory and immunomodulatory functions. Initially, cellular senescence manifested as irreversible cell cycle arrest, but now it encompasses a broader phenotype regulated by the p53-p21CIP1 and p16INK4A-Rb pathways. Although secretory phenotypes related to aging can recruit immune effectors to clear new tumor cells, persistent senescent cell populations often trigger chronic inflammation, promoting immune escape and fibrosis. In this review, we first discuss the molecular underpinnings of cellular senescence, highlighting its induction pathways and diverse physiological or pathological roles. We then examine the composition of the tumor microenvironment, where senescent cells accumulate and secrete pro-inflammatory cytokines, reshaping immune surveillance and extracellular matrix architecture. Against this backdrop, we explore how aging clocks refine our understanding of individual susceptibility to malignancy by distinguishing biological from chronological aging. We also present current therapeutic prospects, including senolytic agents targeting senescent stromal cells that promote tumor growth, and the utilization of aging clock metrics to tailor immunotherapies more effectively for older patients. Finally, we consider the major challenges facing clinical translation, from standardizing multi-omics data pipelines to clarifying the ethical implications of measuring biological age. By bridging senescence biology with geroscience and cutting-edge oncology, we posit that aging clocks may catalyze a transformation in cancer care, enabling more personalized, effective, and age-conscious treatment strategies.

Aging | doi:10.18632/aging.206318. Takashi Ohira, Naoyuki Kawao, Yuya Mizukami, Kiyotaka Okada, Akihito Nishikawa, Hisatoshi Yamao, Ayaka Yamada, Hiroshi Kaji

Aging is a complex process resulting in a decline in organ function. Here the authors proposes that chronic activation of tissue damage response mechanisms drives aging, with aged organs displaying features similar to those seen after acute injury. This provides a unifying framework for understanding the aging process and suggests new directions for treating age-related diseases.