Aging & Longevity

Adult hippocampal neurogenesis declines with age, but the stress pathways that shape neural precursor cell (NPC) survival and lineage progression remain incompletely understood. Here, we tested whether ferroptosis-related vulnerability contributes to the regulation of hippocampal NPCs and their progeny. Using in vitro assays, transcriptomic analyses, and in vivo genetic and pharmacologic perturbations, we find that NPCs show features consistent with elevated susceptibility to ferroptotic stress...

Somatic stem cells are characterized by their low overall protein-synthesis rates, a feature implicated in driving their stemness. However, how aging reshapes the translational landscape of stem cells remains poorly understood. Here, we present an in vivo single-cell ribosome profiling strategy to monitor tissue-wide translational landscapes of the epidermis during aging. By implementing ribosomal elongation-inhibited cell isolation and switching to RNase I, we expand the applicability of...

Nutritional support for healthy aging is an active field of research. Bovine organ extracts, and glandular therapy in general, became popular in the 1900s, but their effect on healthy aging is unexplored, and their mechanisms of action are unclear. Here, we evaluated three bovine thymus materials with regards to their effect on healthy aging in C. elegans: two thymus extracts, a nuclear fraction (TNF) and a cytosolic fraction, and desiccated bovine thymus. All three materials extended C. elegans...

The aim of this study was to evaluate the effects of prolonged exposure to hypertriglyceridemia induced by overexpression of the human apolipoprotein CIII (apoCIII) gene, as well as the impact of age, on the liver of genetically modified mice. A total of 32 male mice, aged 5 and 20 months, were divided into transgenic (CIII) and non-transgenic (NTG) groups. Biochemical analyses of blood and morphological assessments of liver and adipose tissue were performed. ApoCIII overexpression resulted in...

Circulating proteins provide insights into an individual's health and aging trajectory. However, little is known about their long-term temporal stability. We evaluated the five-year temporal stability of 7288 serum proteins in 3093 participants (mean age 75 years) of the AGES-Reykjavik study. We observe wide variability in protein temporal stability, independent of transcriptomic stability in tissues. Temporally stable proteins tend to be extracellular, secreted, and tissue-specific, while...

Human immune responses vary across individuals due to both genetic and environmental factors. We previously established the Milieu Intérieur cohort to define boundaries of healthy immune variation and identify their determinants. To evaluate how immune responses change over time and test whether immune states can predict future disease, we conducted a 10-year follow-up of the cohort. Here we show widespread changes in humoral responses to pathogens over this period, including unexpected...

Carbon membranes yielding high selectivity as well as high permeance are attractive to advance the membrane-based gas separation. Herein, we report ultrathin carbon membranes (UCMs) which deliver enhanced gas separation performance through oxygen-modulated pyrolysis of poly(4-vinylpyridine) precursor. We show that O(2) in pyrolysis environment, transforms the otherwise uniform carbon network featuring a ~ 3.9 Å characteristic interlayer spacing into disrupted UCMs (d-UCMs). These d-UCMs possess...

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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