Aging & Longevity

Chronological age incompletely captures heterogeneity in biological aging. In this prospective study of 45,819 UK Biobank participants, we developed a multimodal ocular aging index (MOAI) by integrating ophthalmic phenotypes with plasma proteomic and metabolomic profiles using machine learning. The MOAI quantifies divergence between ocular biological and chronological age. Over 13.80 years of follow-up, accelerated ocular aging was significantly associated with higher risks of incident...

Nanoscale twin boundaries (TBs) effectively restrict the free motion of dislocations by intersecting with other TBs to realize high strength. However, the dislocations parallel to the TBs can glide along the TBs, resulting in detwinning for low strength. Herein, we present a triple-interlocked-nanotwinned (TIT) strategy for overcoming these inherent deficiencies. An Mg-9Li alloy was used as a proof-of-concept. The treated alloy had a large volume fraction of TIT interfaces (65.7%). It not only...

Amino acids are fundamental to human physiology, yet their impact on growth, development, and aging remains elusive. Here, we introduce AmiAge, a biological age predictor constructed using a Random Forest model trained on the concentrations of 18 amino acids across individuals aged 1 to 89 years. Leveraging data from 9 studies encompassing over 11,000 in-house and more than 270,000 publicly available samples with diverse demographic and genetic backgrounds, AmiAge demonstrates robust accuracy....

Mammals share a laminar cerebral cortex, with excitatory neuron subtypes organized in distinct layers. Although this framework is conserved, subtype balance varies markedly between species due to largely unknown mechanisms. Here, we show that species-specific neuronal composition arises from non-uniform scaling of the temporal dynamics of neurogenesis. Comparative histology of eight mammalian species reveals a significant, rat-specific expansion of the deep layer in the somatosensory cortex....

Systemic chronic low-grade inflammation increases with aging and contributes to the risk or progression of a myriad of chronic diseases. Greater midlife inflammation has detrimental effects on future health outcomes. However, few studies have quantified inflammatory markers from midlife longitudinal measurements. Here, we measured cytokines, chemokines, and clinical biomarkers of inflammation at three different time points in a cohort of middle-aged (mean age 48) African American and White men...

Cerebral infarcts in carotid artery disease arise from a complex interplay between plaque vulnerability, extracranial vascular burden, intracranial collateral capacity. Although each of these factors has been studied individually, their combined impact on infarct presence, infarct pattern, and long-term outcomes in real-world carotid endarterectomy (CEA) populations remains insufficiently understood. This study aimed to determine how carotid plaque morphology, bilateral carotid stenosis...

The field of human adult neurogenesis has been controversial despite mounting evidence. The authors propose moving beyond debating the existence of adult neurogenesis and towards discovering strategies to harness endogenous stem cell potential for resilience against cognitive aging.

Aging is increasingly recognized as a dynamic and potentially modifiable biological process, yet translation of mechanistic discoveries into clinically validated interventions that extend human healthspan remains limited. Because dermatologists can directly observe, sample, and quantify age-related changes in vivo, the skin provides an accessible platform for gerotherapeutic evaluation. As the largest and most environmentally exposed organ, the skin integrates intrinsic hallmarks of aging,...

Workaholism, also referred to as problematic overworking, has received increasing attention due to its adverse consequences for individuals, families, and organizations. This perspective paper argues that workaholism represents a largely neglected risk factor for unhealthy aging, as sustained exposure to excessive and compulsive work might be associated with an increased risk of cardiometabolic conditions, including hypertension and cardiovascular disease. We further highlight that, despite the...

Accurate projections of temperate tree growing seasons under climate change require representing developmental constraints that determine tree resource allocation. A phenological 'switch point' after the summer solstice (21 June) has been proposed, with pre-solstice warming advancing autumn phenology and post-solstice warming delaying it. We propose that this switch is flexible and occurs at the compensatory point between early-season development and late-season temperature effects. We performed...

Older adults are highly vulnerable to infectious diseases, and vaccines are often less effective in this population because of diminished B and T cell memory responses driven by impaired autophagy, immunosenescence, and chronic low-grade inflammation. Spermidine has been shown to counteract immunosenescence and induce autophagy in preclinical models, and its levels decline with age in humans. We conducted a double-blind, randomised, placebo-controlled pilot study in 40 adults over 65 years of...

Aging significantly impairs vaccine efficacy in older adults, driven by immunosenescence, inflammaging, and disruptions in the gut microbiota-mTOR-immune axis. This review synthesizes current evidence on how aging alters vaccine-induced immune responses through the interplay of gut microbiota dysbiosis and dysregulated mTOR signaling. Age-related microbial diversity declines and reduced short-chain fatty acid (SCFA) production exacerbate inflammation, while heightened mTOR activity suppresses...

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CONCLUSION: NAC shows potential in modulating mechanisms of muscle deterioration, but evidence remains largely preclinical. Well-designed randomized trials in older adults, particularly with sarcopenia or frailty, are needed.

CONCLUSION: This study provides longitudinal evidence from a large prospective cohort indicating that LHS is an independent predictor of self-reported incident OP in the older population. As a simple and practical tool, handgrip strength testing can aid in the early identification of individuals at high risk for OP in community and clinical settings, providing a basis for implementing targeted preventive strategies, while highlighting the need for future research to confirm the observed...

Transfer RNA (tRNA) halves (tRHs) are generated via the cleavage of tRNAs, but their roles in aging and longevity remain poorly understood. Here, we demonstrate a direct role of tRHs in aging in metazoans. Through a genetic screen using Caenorhabditis elegans, we identify DIS-3/DIS3 as a ribonuclease that catalyzes tRH generation, including 5'-tRH-Gln and 5'-tRH-Asp, from tRNAs. Among them, 5'-tRH-Gln is essential for longevity conferred by various interventions, including dietary restriction....

Limited vaccine availability and logistical barriers during the COVID-19 pandemic have hindered homologous boosting in resource-limited regions. Therefore, heterologous prime-boost regimens have gained attention as versatile and practical alternatives. We evaluated the immunogenicity and longevity of four vaccine regimens in adults from Mozambique and Madagascar: single-dose Ad26.COV2.S (Ad26.S), homologous BBIBP-CorV (BBIBP), and two heterologous combinations (BBIBP-Ad26.S and Ad26.S-BBIBP, in...

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...