Aging & Longevity

Skeletal muscle stem cells (MuSC) are the guardians of muscle regeneration, sustaining tissue integrity through a delicate balance of quiescence, activation, and lineage commitment. While numerous molecular cues have been implicated in regulating these processes, the influence of androgen receptor (AR) signaling, an essential hormonal pathway for male muscle physiology, has remained largely unexplored. Here, we show that AR expression defines quiescent MuSC and acts as a safeguard of their...

Proteins generally begin with methionine, which is often removed to expose the second residue. RuBP carboxylase/oxygenase (Rubisco), the most abundant enzyme on Earth and a major carbon and nitrogen reservoir, escapes this paradigm. Its catalytic subunit, RbcL, undergoes unusual amino terminal maturation, including atypical initiator methionine-serine cleavage and proline acetylation, a modification not seen in other biological systems. We define a specialized pathway of two sequential...

ObjectiveThis study examines how life expectancy (LE) without and with depression differs by living arrangement among older adults in Japan, with particular attention to gender differences.MethodsData were drawn from the Nihon University Japanese Longitudinal Study of Aging (1999-2009). Multistate life table methods were used to estimate LE spent without and with depression among adults aged 65 years and older across different living arrangements.ResultsPronounced gender differences were...

Limbal niche cells (LNCs) serve as essential regulators of limbal microenvironmental homeostasis and corneal epithelial wound repair, representing a promising therapeutic resource for limbal stem cell deficiency (LSCD). However, their clinical application is constrained by replicative aging during in vitro expansion. In this study, we investigated whether a three-dimensional (3D) Matrigel-based culture system could modulate replicative aging in LNCs. Compared with conventional two-dimensional...

The female brain undergoes substantial reorganization during major hormonal transitions, yet whether puberty, pregnancy, and menopause engage shared or distinct neuroplastic mechanisms remains unknown. We compared longitudinal structural brain changes across all three major hormonal life events using identical analytical methods within a single cohort framework (n = 1095), with stable control groups to control for normative developmental and aging trajectories. Both pre-to-post menarche and...

Endocrine organs translate nutrient, stress and circadian cues into hormone outputs that coordinate whole-body physiology. Cellular senescence can distort this communication by changing endocrine-cell identity, stimulus-secretion coupling, secretory timing and local immune or paracrine signaling. Evidence is strongest in pancreatic β-cells and the adrenal zona fasciculata, where composite senescence phenotypes have been linked to endocrine dysfunction and modified by targeted perturbations....

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Retinal pigment epithelium (RPE) senescence acts as a core driver of subretinal fibrosis, a major irreversible pathological feature that exacerbates age-related macular degeneration (AMD). Mitophagy is essential for maintaining RPE homeostasis during aging. However, the upstream molecular mechanisms underlying mitophagy impairment in senescent RPE remain poorly defined. Here, we show that lysosomal-associated transmembrane protein 5 (LAPTM5) is significantly upregulated in human AMD specimens...

Obstacles to translation elongation stall ribosomes and allow deleterious proteins to accumulate, which threatens cellular health. Cells recognize and clear stalled ribosomes via several interrelated pathways, although the mechanisms by which cells distinguish stalled from normally elongating ribosomes and mount an appropriate response are incompletely understood. While recent work highlights how ribosome collisions help cells to recognize stalled ribosomes, how other factors contribute to...

CONCLUSION: The group-level spatial map showed exploratory correspondence with selected normative functional connectivity (FC)- and structural connectivity (SC)-based candidate profiles. Individualized profiles showed greater cross- sectional correspondence with the selected SC-based profile than with the FC-based profile, providing a network-informed description of diabetic brain alterations.

CONCLUSION: Adult hearing loss is significantly associated with increased risks of cognitive impairment and dementia. These findings highlight the importance of hearing health in cognitive aging and support further prospective and interventional studies.

The core genes of the circadian pathway, such as Timeless(Tim), not only participate in the regulation of biological rhythms, but also play significant roles in DNA damage repair, chronic inflammation, and cellular metabolism. However, it remains unclear whether exercise can delay the age-related phenotypic degeneration by regulating the muscle Tim gene. In here, we first carried out the expression regulation of the muscle Tim gene in the Drosophila by constructing the Mhc-gal4/Tim-UAS system,...

Mutations are fundamental to oncogenesis, yet they cannot fully explain cancer progression, as oncogenic mutations frequently accumulate in healthy tissues without immediate malignancy. In the liver, β-catenin mutations are highly prevalent in hepatocellular carcinoma but are widely considered weak or cooperative drivers, raising the question of how their oncogenic potential is contextually regulated. Aging and chronic injury are major determinants of cancer risk. However, how declining tissue...

Millions of people worldwide suffer from sarcopenia, a clinically recognized syndrome that is defined as the age-related loss of skeletal muscle mass and strength. Sarcopenia reduces mobility, leads to falls and fractures, and increases the risk of death, posing an ever-increasing health-care and economic burden to society. There are currently no approved therapies for the syndrome, partly owing to its multifactorial aetiology, highlighting the need for therapies with pleiotropic beneficial...

Drugs for aging-related diseases may modulate aging itself, but standard clinical trial designs cannot detect such effects. Aging clocks could close this gap, but epigenetic models often yield inconsistent, hard-to-interpret results. In contrast, proteomic clocks, by tracking the immediate effectors of biological change, may excel in providing aging biomarkers or mechanistic insight. Here we compare six proteomic clocks (ProtAge, OrganAge(mortality), OrganAge(chrono), PAC, ipfP3GPT and PAOPAC)...

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There is increasing recognition that a broader array of biological changes may contribute to the clinical expression of cognitive decline. As such, an emerging and often overlooked consideration in dementia is apathy, gait dysfunction, motoric-cognitive risk syndrome, and their interplay. Broadly, apathy, gait dysfunction, and motoric-cognitive risk may reflect changes across multiple physiological and neural systems acting as clinical markers bridging normal aging and overt dementia, thereby...

Antibody imprinting is well recognized, yet its long-term dynamics and epitope specificity remain poorly understood. Here, we studied individuals sequentially infected with SARS-CoV-1 (SARS-1) and SARS-CoV-2 (SARS-2) over two decades and found durable imprinting of antibody responses following SARS-2 BF.7 breakthrough infection. Approximately 60% of isolated monoclonal antibodies were SARS-1 imprinted and targeted conserved receptor-binding domain regions, whereas 37% overcame imprinting to...

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases, and its pathogenesis and treatment strategies remain major challenges. Recent advances in single-cell RNA sequencing and lineage tracing have revealed that vascular smooth muscle cells (VSMCs) are not merely passive structural components of atherosclerotic plaques, but highly plastic participants that undergo clonal expansion, phenotypic modulation, and transdifferentiation into functionally diverse cell states....