Aging & Longevity

Immunosenescence is not a uniform decline but a trajectory shaped jointly by age and sex. Using continuous high-dimensional immunophenotyping, we show that aging T cells accumulate a senescent signature of CD28 loss and CD57 gain, and that males reach an inverted CD4:CD8 ratio earlier and more severely than females. We argue that age-by-sex stratification should guide vaccination and geroprotective strategies in an aging population.

Aging biomarkers can potentially allow researchers to rapidly monitor the impact of an aging intervention without the need for decade-spanning trials. However, before the use of aging biomarkers, such as epigenetic clocks, as surrogate endpoints, their responsiveness to interventions that target aging must be tested. Here we curate TranslAGE, a harmonized database of 51 public and private longitudinal interventional studies, and calculate a consistent set of 16 prominent epigenetic clocks for...

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Frailty and cognitive impairments frequently co-occur in older adults. It remains unclear whether this overlap reflects shared underlying biological mechanisms or parallel but distinct disease pathways. We hypothesize that physical weakness and cognitive impairment share circulating markers already in an early disease stage. We therefore recruited and analyzed a relatively healthy population with partially overlapping pre-frailty and mild cognitive impairment (MCI), and applied a multi-omics...

Family dogs' human-analogue attachment to the owner has long been recognised; however, how this dog-owner attachment develops and changes with age remains an open question. We examined age-related variation and the effect of training experience on the attachment behaviour in family dogs (N = 222) using the Strange Situation Test (SST). Across three age groups (puppy-juvenile, adult, and senior dogs), dogs were assessed by scores for three behavioural factors: attachment to the owner, anxiety...

The increase in life expectancy over the past century has been accompanied by the recognition of age as the primary risk factor for a wide range of pathologies, including cardiovascular and neurodegenerative diseases, as well as cancer. Thus, the development of interventions that slow the underlying biological processes of aging could have beneficial effects on the prevention or progression of these diseases. To evaluate such geroprotective interventions, quantifying biological damage via aging...

Population aging is accompanied by a parallel increase in cardiovascular disease (CVD), vascular cognitive impairment (VCI), and dementia, highlighting the urgent need to better understand the complex interactions linking cardiovascular, cognitive, and emotional health. Growing evidence suggests that cardiovascular dysfunction, emotional dysregulation, and cognitive decline are not isolated conditions but interconnected manifestations of shared vascular, inflammatory, neurohumoral, metabolic,...

Chronic diseases can continue to progress after the initiating insult has subsided, indicating that injured tissues may retain a persistent imprint of failed repair. Here, senescent repair memory refers to a tissue state in which transient repair-associated senescence fails to resolve and is maintained by persistent senescent cells, altered secretory and metabolic programmes, defective immune clearance, epigenetic stabilization and spatial niche interactions. Once established beyond the adaptive...

Ageing is a process of continuous decline of cellular health. This decline could be attributed to loss of functions to various crucial protein players regulating the triage of cellular physiology. Systematic decline of cellular proteostasis is one major change that orchestrates alterations in functioning of other biological indicators, including cellular energetics, signal transduction, and metabolic adaptation. Among many molecular players governing physiological changes, E3 ubiquitin ligases...

Biomass burning organic aerosol (BBOA) is a major source of atmospheric brown carbon (BrC), which contributes to climate through solar radiation absorption. Chemical aging (bleaching) of BrC diminishes light absorption over time. Although recent modeling studies have emphasized the need to account for bleaching when assessing BrC's climate impacts, a parameterization representing the entire BBOA matrix has been lacking. Here, we develop a bleaching parameterization for the whole BrC in BBOA...

Hematopoietic stem cells (HSCs) constitute an organized hematopoietic system that undergoes age-related alterations, including increased platelet production and decreased erythropoiesis. The fundamental mechanisms driving these shifts remain incompletely understood. We used single-cell RNA sequencing data to show that old HSCs contain two distinct transcriptional programs: one shared with megakaryocytes and the other reflecting the most primitive HSC state. Developmental time-series profiling...

CONCLUSION: This study established preliminary, cohort-specific multi-regional ¹H-MRS reference estimates for cognitively intact older adults, with robust regional profiles and large effect sizes. The PCC showed exploratory age-related change-most consistently a coordinated aspartate-glutathione decline-requiring confirmation in larger cohorts, whereas the OC emerged as a candidate metabolically stable region.

Miscarriage and abnormal embryonic development in women of advanced maternal age (AMA) are often associated with impaired decidualization. mTORC2 is an evolutionarily conserved protein kinase. As a core component of mTORC2, RICTOR has been implicated in nutrient sensing and is closely linked to implantation disorders; however, its role in regulating age-related decidualization disorders remains unreported. In this study, we identified pronounced decidualization defects in AMA foster mice,...

Cellular senescence is a fundamental hallmark of aging and represents a major barrier to the scalable and reproducible application of mesenchymal stromal cell (MSC)-derived small extracellular vesicles (sEVs). Senescent human umbilical cord mesenchymal stromal cells (hUCMSCs) exhibit impaired proliferative capacity, disrupted mitochondrial homeostasis, and altered secretory phenotypes, which may compromise the biological activity and therapeutic reliability of sEVs. Here, we investigated whether...

Aging is accompanied by arterial dysfunction, defined by impaired endothelial function and increased large artery stiffness, yet the contribution of the endothelial glycocalyx (eGC) and its constituent, hyaluronan (HA), to this process remains incompletely understood. We tested the hypothesis that decreasing endothelial HA synthesis via a reduction in endothelial-specific HA synthase 2 (HAS2) compromises eGC integrity and contributes to arterial dysfunction with advancing age. Both...

Ageing impairs immune function, increasing susceptibility to infection, autoimmunity and inflammation. The thymus undergoes involution during childhood, and thymocyte and thymic epithelial cell (TEC) numbers decline. Given that adaptive immunity depends on T-cells recognising diverse antigens via their unique T-cell receptor (TCR), the precise age-related changes in TCR repertoire composition are key to understand immunity. To investigate the influence of age on the thymic TCR repertoire we...

Age-related taste dysfunction impairs nutrition and quality of life, contributing to metabolic disorders and frailty in the elderly, yet its cellular and molecular basis remains poorly understood. By integrating single-cell RNA and spatial transcriptomics sequencing, we systematically mapped murine taste bud aging across five developmental stages from neonatal to aged. Our findings reveal that age-associated taste impairment is driven by the progressive depletion of stem/progenitor cell...

The clinical outcomes of trabeculectomy, a standard glaucoma filtration surgery (GFS), have dramatically improved with the introduction of mitomycin C (MMC), an antimetabolite widely used to inhibit postoperative scarring. MMC exerts anti-scarring effects primarily by promoting apoptosis and suppressing fibroblast proliferation at the surgical site. However, despite these beneficial effects, MMC also induces the production of inflammatory cytokines, and its full mechanism of action remains...

Redox imbalances and mitochondrial dysfunction are key contributors to age-related declines in skeletal muscle and may contribute to impaired exercise responsiveness. Here, we investigated the influence of aging on skeletal muscle redox at rest and in response to acute exercise, examining how mitochondrial quality and quantity relate to skeletal muscle redox status. Skeletal muscle biopsies were obtained from 12 young (22 ± 4 years) and 10 older adults (66 ± 7 years) before and immediately after...