Aging & Longevity

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...

Mammalian cochlear hair cells convert acoustic stimuli into electrical signals, which are relayed to the central auditory pathway via auditory neurons. Progressive loss of hair cells and their synapses is a characteristic of age-related hearing loss (ARHL), but the underlying mechanisms remain poorly understood. In this study, we tested the hypothesis that hair cell physiological properties change with age in CBA/CaJ mice, a strain known for its slow ARHL progression. We found that hair cell...

Skeletal muscle is a central determinant of organismal health. Preserving muscle quality is therefore critical for preventing disease and sustaining quality of life across the lifespan. Despite its central role, the field lacks a unifying framework that defines the core properties of skeletal muscle health. Here, we propose a conceptual framework for muscle homeostasis built around seven interconnected hallmarks-metabolism and bioenergetics, proteostasis, genomics, excitability, structure,...

Cellular senescence contributes to aging and age-related diseases by driving chronic inflammation through the senescence-associated secretory phenotype (SASP), including interferon-stimulated genes (ISGs). Here we confirm and extend previous observations that cyclin D1 (CCND1), a key cell cycle regulator, is paradoxically upregulated across models of nonproliferating senescent cells. We show that CCND1 and its kinase partner CDK6 drive SASP and ISG expression in senescent cells by promoting DNA...

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Neurodegeneration is increasingly recognized not only as a disorder of neurons but also as a breakdown of dialogue between the nervous and immune systems. Recent discoveries reveal that immune cells and inflammatory signals are deeply interwoven with brain function across the lifespan. Far from passive responders, immune cells act as sentinels and shapers of neuronal resilience, vulnerability, and repair. Together, robust data support a model in which neurodegeneration emerges from complex...

Previous studies predominantly associated lymphatics with skeletal disease and bone loss. However, building on our work, bone lymphatics are emerging as a paradigm-shifting component of the skeletal microenvironment, illustrating their role as positive regulators of bone mass and repair. Here, we present a comprehensive analysis integrating spatial transcriptomics, single-cell RNA sequencing, and imaging across murine and human bones. Spatial transcriptomics identifies Prox1^(+) endothelial...

Genotoxic drugs induce apoptosis-resistant senescent "zombie" cells. In this issue of Cell Chemical Biology, Gallagher Aldave et al.¹ show that these cells acquire dependence on BCL-xL and MCL-1, creating a therapeutic vulnerability to their inhibitors and degraders.

Degenerative diseases progress through gradual cell-intrinsic damage that is difficult to resolve with bulk transcriptomics or discrete cell-state analysis. We introduce a generalizable single-cell and spatial transcriptomics framework that quantifies continuous damage trajectories in vivo using cell-type-specific scores. Applied to chronic kidney disease and metabolic dysfunction-associated steatotic liver disease, the podocyte damage score (PDS) and hepatocyte damage score (HDS) place...

Neurodegenerative diseases associated with ageing are characterized by progressive neuronal dysfunction and loss, yet effective disease-modifying therapies remain elusive. Increasing evidence indicates that mitochondrial dysfunction is not merely a downstream consequence of neurodegeneration but represents an early and active driver of disease initiation and progression. This review addresses this critical gap by establishing an integrated framework that systematically connects mechanistic...

Ageing is a fundamental biological process marked by declining physiological function and the accumulation of stress-induced damage. It contributes to chronic disease and drives widespread alterations across organ systems, including the vasculature. Ageing of the macro- and microvasculature impairs nutrient delivery, promotes tissue degeneration, and reduces repair capacity in many tissues, including those of the musculoskeletal system. Tendons and ligaments become increasingly injury-prone with...

Aging is associated with blood-brain barrier (BBB) breakdown and microvascular rarefaction, key contributors to cerebral neuroinflammation, hypoperfusion, and vascular cognitive impairment and dementia (VCID). Exposure to a young systemic milieu through heterochronic parabiosis has been shown to restore BBB integrity and enhance cerebrovascular function in aged mice, suggesting that circulating factors can rejuvenate the aging brain. However, the molecular mediators responsible for these effects...

While aging is the greatest risk factor for the development of neurodegenerative disease, the role of aging in these diseases is poorly understood. Our previous work has shown that targeting aging pathways can be neuroprotective in animal models of neurodegenerative disease. Based on these findings, we believe that by gaining insight into the aging process that knowledge can be applied to identify novel therapeutic targets for neurodegenerative disease. To advance our understanding of aging, we...