Aging & Longevity

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%),...

Sex differences in obesity are well recognized; however, the identification of sex-specific obesity genes and the mechanisms through which they affect obesity development remain elusive. Here, we identify a germ-cell-specific gene C2orf74, whose expression is responsive to high-fat diet (HFD) and promotes HFD-induced obesity in male mice by restraining lipolysis and limiting the browning of white adipocytes through suppression of androgen receptor signaling, but not in females. Additionally,...

Skin aging, the most visible and accessible manifestation of organismal aging, reflects systemic physiological decline, compromising barrier integrity, immune defense, and regenerative capacity-functions essential for overall tissue homeostasis and longevity. Understanding why and how the skin ages offers crucial insights into tissue homeostasis and systemic aging. Here, we dissect the multi-layered mechanisms of skin aging across the epidermis, dermis, and appendages, highlighting how intrinsic...

Programmed degradation of maternal proteins is essential for the oocyte-to-embryo transition (OET). While pharmacological inhibition studies have established the importance of proteasomes in ovarian reserve maintenance, oocyte maturation and fertilization, the physiological impact of intrinsic proteasome insufficiency and underlying molecular mechanisms remain poorly understood. In mice, endolysosomal vesicular assemblies (ELVAs), specialized membraneless compartments composed of proteasomes,...

Identifying physiological sweet spots (optimal ranges for homeostasis) is essential for precision medicine. However, traditional statistical methods often rely on globally linear or locally jagged models that struggle to capture the smooth, non-linear nature of biological regulation in high-dimensional data. We present the Quantile Feature Selection Network (Q‑FSNet), a neural network-based framework that integrates quantile regression, feature selection, and uncertainty estimation to identify...

INTRODUCTION: Physical activity may enhance cognition in older adults, yet evidence from randomized controlled trials (RCTs) on mechanistic pathways remains inconclusive.

During wakefulness, neuromodulators operate largely independently to support behavior and cognition. By contrast, sleep reorganizes their activity into a coordinated brain rhythm. During sleep, the major neuromodulators-norepinephrine, acetylcholine, serotonin, and dopamine-exhibit synchronized fluctuations with a periodicity of ~50 seconds. These oscillations appear as recurrent bursts of fast (10 to 30 hertz) electroencephalography activity and are phase-coupled to cerebrospinal fluid flow....

In this cross-sectional cohort we analyzed data from 4260 "health enthusiasts" who purchased at least one saliva-based DNA epigenetic test between 2020 and 2025 and completed detailed lifestyle and supplement questionnaires. A proprietary 9-CpG clock with a mean absolute error of 5.4 years served as the primary biomarker of biological age. High prevalence (71%) of supplement use in this cohort increased our power to study the effects of supplements compared to earlier studies that focused on the...

T cells are central to adaptive immunity, and continuously sense, generate, and respond to mechanical forces. Advances in mechanoimmunology show that T-cell behavior is tightly shaped by the physical properties of their environment, including stiffness, viscoelasticity, ligand arrangement, and tissue topography. T-cell activation depends not only on biochemical signals but also on forces transmitted through the T-cell receptor, coreceptors, and mechanosensitive ion channels, which converge on...

CONCLUSIONS: Living arrangement, social activity and residence were the most significant factors associated with the types of LTC utilization by older adults in China. Overall, enabling and predisposing factors had a greater influence than the need factors. These findings not only demonstrate the potential value of ML for LTC policy development, but also provide empirical support for the Chinese government to adopt targeted interventions that enhance LTC service accessibility and affordability.

Transcription factor (TF) modules interact to regulate key biological processes and cell-state transitions in normal physiology and disease. Understanding these modules and how they evolve over time can be accomplished by constructing gene regulatory networks (GRNs). To identify context-specific TF subnetworks, we developed ChEA-KG, which generates enriched TF regulatory subnetworks for input gene sets. ChEA-KG is based on a GRN connecting 1559 human TFs via 131 181 signed and directed edges...

Cellular senescence induced by internal and external stimuli features stable cell cycle arrest and SASP, closely linked to aging and various age-related diseases. It is accompanied by lipid metabolism disorders and epigenetic abnormalities, which interact closely to modulate senescence. This review summarizes their crosstalk in senescence and relevant diseases, aiming to offer new insights and therapeutic targets for alleviating cellular senescence and treating age-related diseases.

Intestinal stem cells (ISCs) continuously renew the gut epithelium by producing specialised cell types, yet the mechanisms that couple ISC renewal with lineage commitment remain poorly characterised. Here, we identify a self-limiting transcriptional program, mediated by the zinc-finger transcription factor Chronophage (Cph), that promotes both ISC maintenance and differentiation into enteroendocrine (EE) cells in the Drosophila midgut. Cph expression is transiently induced by the proneural...

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Telomere capping largely depends on telomere length. Abnormally short telomeres are prone to activate DNA damage checkpoint, undergo unscheduled chromosomal fusions through nonhomologous end-joining (NHEJ) and be resected. All these processes are mediated by the Mre11-Rad50-Xrs2^(NBS1) (MRX^(MRN)) complex. The response to telomere length is thought to correlate with the number of DNA-bound telomeric proteins but the mechanisms translating this number into functional protection remain unclear....

Recent work leveraging omics and imaging data now enables the estimation of aging at the level of individual organs. Emerging findings suggest that organs age at different rates, which may be linked to environmental exposures and genetic factors. However, premature aging in one organ may also drive aging in connected organs within multi-organ aging networks. Here, we outline methods for measuring organ-specific biological age and discuss insights derived from recent progress in multi-organ aging...

Biological age may provide a more informative metric of individual physiological function and life expectancy, compared to chronological age. Proteomic aging clocks are predictive models trained using high-dimensional proteomic data to quantify biological age. Owing to the central biological role of proteins and their established clinical utility as druggable targets and prognostic biomarkers, proteomics is particularly promising for the assessment of aging. In this Review, we provide an...

Aging impairs coordinated organelle dynamics essential for lipid metabolism, causing a decline in intracellular metabolic flexibility. However, the drivers of organelle collapse and their temporal order remain unclear. Here we identify peroxisomal function as a critical regulator of metabolic flexibility during youth and low-energy states. Using Caenorhabditis elegans, we show that fasting robustly induces peroxisomal function in youth, whereas this response is blunted during aging. Loss of...

Intrinsic capacity (IC) is a crucial determinant of healthy aging, operationalized through five essential functional domains -- locomotion, cognition, vitality, psychological, and sensory capacities. Integrating geroscience principles with IC assessment in preclinical models with accelerated aging profiles can support bidirectional translation. This narrative review aimed to summarize measurement approaches for each IC domain and to show how IC evolves longitudinally in mouse and fish models. A...

CONCLUSIONS: Observational analyses link diabetes and prediabetes to poorer balance performance, and genetic evidence supports an association between diabetes liability and increased fall risk.