Aging & Longevity

Chronic intermittent hypoxia (CIH), a cardinal pathophysiological feature of obstructive sleep apnea (OSA), repeatedly exposes the heart to hypoxia-reoxygenation stress. The cardiac outcome of CIH, however, may depend on the biological state of the target myocardium. Here, we investigated whether a pre-existing aging-related myocardial susceptibility lowers the tolerance threshold for CIH-induced injury and whether Dynamin-related protein 1 (Drp1) contributes to the enhanced vulnerability of...

INTRODUCTION: The ability to perceive spatial changes is crucial for everyday life. However, the effects of age on multisensory integration in spatial change detection are still less researched. Here, we investigated whether audio-visual stimulation enhances spatial change detection compared to auditory-only processing, and whether older adults benefit more from multisensory stimulation than younger adults.

Stem cell-based therapies show promise for tissue regeneration but are limited by therapeutic instability, particularly in aged tissues. Here, multi-omics profiling of regenerating bone reveals marked depletion of S-adenosylmethionine (SAM), indicating epigenetic dysregulation associated with impaired repair. To address this, we develop a spatially compartmentalized, fusogenic nanovesicle system (SMNV), termed a "nanoconcentrisome," composed of SAM-loaded fusogenic liposomes encapsulating...

Aging is a complex biological process governed by conserved genetic and metabolic pathways. Increasing evidence has identified the gut microbiota as a critical modulator of host aging and healthspan. The Caenorhabditis elegans model provides a powerful system to elucidate the molecular determinants of this cross-kingdom dialogue. Recent advances in this model organism reveal that gut microbes may regulate aging through two distinct yet convergent mechanisms: (i) the production of small-molecule...

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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...