Aging & Longevity

Somatic mosaicism originates from postzygotic errors and creates a unique genomic landscape in every cell and individual. The health impacts of somatic mutations range from neutral to severe, responsible for most cancers and contributing to neurodevelopmental, neurodegenerative and other multifactorial diseases. The molecular mechanisms driving this variability are diverse, dominated by replication errors of DNA polymerase ε in CpG contexts and by spontaneous cytosine deamination followed by...

Sarcopenia is characterized by the progressive loss of skeletal muscle mass and strength, accompanied by impaired regenerative capacity. This study examined age-related changes in skeletal muscle regeneration and the associated expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and myogenin (MyoG). Male C57BL/6 mice aged 3, 13, and 23 months were subjected to barium chloride (BaCl(2))-induced tibialis anterior muscle injury. In parallel, C2C12 cells were exposed to...

Acute liver failure (ALF) is a life-threatening condition often leading to hepatic encephalopathy (HE), a neuropsychiatric disorder characterized by cognitive deficits and motor dysfunction due to elevated ammonia levels and neuroinflammation. This study investigates the therapeutic potential of resveratrol (RSV), a SIRT1 activator, in mitigating the cognitive and motor impairments associated with ALF-induced HE. SIRT1 is an NAD+-dependent class III histone deacetylase and mammalian ortholog of...

Aging is an inevitable physiological process characterized by progressive functional decline and degenerative alterations across organ systems. Metabolic disturbance, particularly the disruption of substance and energy metabolism, is increasingly recognized as a central hallmark of aging. Emerging evidence suggests that dysregulation of the urea cycle (UC) contributes to aging-related pathological processes, including cognitive impairment; however, its role in astrocyte-mediated brain aging...

CONCLUSIONS: In this nationally representative cohort, high psychological resilience measured before death was associated with lower symptom burden across multiple domains in the last year of life. Resilience assessment may help identify individuals at risk for distressing end-of-life experiences and inform interventions to bolster late-life resilience.

DNA damage is considered one of the major contributors to aging. DHCR24, a multifunctional enzyme located within the endoplasmic reticulum (ER), is closely related to DNA damage. Our previous study showed that DHCR24 could delay vascular endothelial cells (ECs) senescence. The relationship between DHCR24 and DNA damage during ECs senescence requires further investigation. Here, we demonstrate that aging activates ATM-mediated DNA damage response (DDR) in human umbilical vein endothelial cells...

Aging is a major contributor to the increasing incidence of acute kidney injury (AKI) and chronic kidney disease (CKD), however the molecular events explaining aging-related nephropathies remains elusive. Here, we found that the RAS signaling adapter protein Erbin (ErbB2-interacting protein) is abundantly expressed in renal tubular cells, but its levels are decreased in murine AKI models and human CKD patient samples. Tubule-specific deletion of Erbin rendered mice highly susceptible to acute...

Healthy aging is associated with structural and functional brain changes. However, cognitive abilities vary in how they change with age: executive functions decline, while aspects of linguistic processing remain relatively preserved. This heterogeneity predicts differences among brain networks in whether and how they change with age. To evaluate this prediction, we used precision fMRI to examine the language-selective network and the Multiple Demand (MD) network, which supports executive...

Food insecurity is increasingly recognised as a public health concern among older adults, yet the mechanisms linking it to mortality remain unclear. Gianfredi and colleagues recently examined this association using data from the English Longitudinal Study of Ageing (ELSA), reporting that food insecurity was associated with a 41% higher risk of all‑cause mortality and a 126% higher risk of premature mortality (before age 75). While the study addresses an important question using a large,...

Pancreatic cancer remains at a stagnant 5-year survival of <13%, attributed to the high heterogeneity and plasticity of these tumors. To circumvent this, we focus on the abundant nuclear protein high mobility group-box protein 2 (HMGB2). HMGB2 depletion is key for establishing replicative senescence in normal cells, but it is significantly overexpressed across multiple cancer types. Here, we combine single-cell and spatial genomics with patient-derived organoids and tumor samples to show how...

Considerable progress in oncology has substantially reduced cancer-related mortality, as reflected by the growing number of cancer survivors. In this context, the management of adverse events associated with cancer treatments has become even more important. Small-molecule VEGFR inhibitors are associated with clinically relevant cardiovascular and hepatic adverse events, including arrhythmias, heart failure, liver enzyme elevations, and hepatic failure. This review integrates the clinical...

Human menopause and the prolonged post-reproductive lifespan (PRLS) are distinctive features of female aging with profound implications for long-term health. Evolutionary theories, such as the Grandmother Hypothesis and other models (e.g., intergenerational reproductive conflict), suggest menopause evolved under ancestral conditions of high extrinsic mortality in early life, short lifespans, and inclusive-fitness benefits derived from kin investment. In such environments, postmenopausal survival...

Cellular senescence is characterized by cell cycle arrest accompanied by mitochondrial dysfunction. Despite extensive efforts to overcome this stable state of growth arrest, effective strategies for treating cellular senescence have not been identified. In this study, we screened plant-derived secondary metabolites and confirmed that formononetin is a substance that potently induces the proliferation of senescent fibroblasts. Formononetin-induced proliferation was associated with the suppression...

Distinct behaviors require the nervous system to execute specialized motor programs, each characterized by unique patterns of body muscle coordination. Whether the execution and adaptation of these programs follow conserved principles across species and perturbations remains unclear. To compare motor programs across species, perturbations, and behaviors, we developed the Python toolbox Automated Gait Analysis (AutoGaitA). Using AutoGaitA and inferring from kinematics, we found that locomotor...

Aging increases tendon injury incidence and poor repair outcomes, but age-related differences in tendon mechanical properties and underlying mechanisms remain unclear. We first analyzed data from the Global Burden of Disease (GBD) database to characterize the associations between aging and population-level changes in tendon injury burden. We found the age-standardized incidence rate (ASIR) of tendon injuries caused by mechanical force decreased with advancing age, whereas the age-standardized...

Epigenetic aging biomarkers are well-established hallmarks of biological aging, yet their metabolic underpinnings remain largely unexplored. Here, we characterized metabolic signatures associated with five epigenetic aging biomarkers (HorvathAge, HannumAge, DNAmPhenoAge, DunedinPACE, and DNAmTL) and examined their clinical relevance and potential determinants in 7162 Chinese older adults from two cohorts (primary and validation). We observed both shared and distinct metabolic associations across...

CONCLUSION: Protein C activity was consistently associated with stroke severity and may reflect endogenous anticoagulant balance. An association with functional outcome was also observed, although this finding was less consistent across sensitivity analyses. These findings suggest that variation in protein C activity across its observed distribution may provide information that is not fully reflected by conventional laboratory reference categories.

Perceptual decision-making (PDM) - the transformation of sensory input into behavioral choice - declines with healthy aging, leading to slower responses, altered accuracy, and negative impacts on quality of life. Recent advances in model-based cognitive neuroscience, particularly drift-diffusion models (DDMs), allow decomposition of PDM into latent components (e.g., evidence accumulation, decision caution, non-decision time) and enable identification of neural circuits associated with each...

Understanding how secreted factors from aged tissue, often referred to as the senescence-associated secretome, reshape cellular phenotypes remains a major challenge due to the complexity of downstream molecular cascades. Here, we present a computational framework for in silico perturbation modeling designed to predict distinct transcriptional responses to age-specific extracellular environmental cues. We exemplify applications of this framework using articular chondrocytes exposed to secretomes...

Aging is a complex biological phenomenon. Because health can vary greatly even among persons of the same chronological age, biological age, an integrative measure of physiological and molecular deterioration, may be a more useful construct for promoting longevity. Biological aging does not represent a "fixed" process; rather, it can be reversible. Many markers of biological aging exist. Epigenetic clocks use patterns of aging-related DNA methylation to predict morbidity and mortality, but other...