Aging & Longevity

CONCLUSION: These findings tie signBrake performance costs to weaker preparatory control differentiation and altered post-stimulus dynamics that support braking under interference. This reduced flexibility may contribute to age-related declines in driving safety in moments that call for rapid, goal-directed control.

Notch1 and vascular endothelial growth factor-A (VEGF-A) are polyfunctional signaling molecules that can be activated in response to elevated shear stress. In nonpathological conditions, they are integral to healthy endothelium; however, it is unknown whether their responsiveness during aerobic exercise, a robust shear stimulus, is impacted by age. Accordingly, in this exploratory cross-sectional study, concentrations of VEGF-A and Notch1 extracellular domain (NECD) were quantified in...

Alzheimer's disease remains a major neurodegenerative disorder for which effective disease-modifying treatments are limited. Adeno-associated virus-mediated gene therapy provides a strategy for sustained modulation of disease-related pathways in the central nervous system. Recent studies have explored this approach for regulating amyloid-β (Aβ) metabolism, tau pathology, neuroinflammation, genetic risk factors and neurotrophic support. This review summarizes the biological basis for...

Mitochondrial dysfunction drives scleroderma pathogenesis. The mitochondria-associated endoplasmic reticulum membrane (MAM) regulates mitochondrial function. Parthenolide (PTL) has protective effects on mitochondria. However, its specific role and mechanisms in localized scleroderma (LoS) remain unclear. This study investigates whether PTL reduces senescence and skin fibrosis by stabilizing MAM in LoS and examines the protective effects of a synthesized thermosensitive controlled-release...

Aging is accompanied by progressive immune remodeling and functional decline across multiple organs. However, the role of neutrophils and their heterogeneous states in these processes remains incompletely understood. Here we integrated single-cell RNA sequencing datasets from multiple organs of young and aged mice to characterize aging-associated neutrophil remodeling. We identified organ-dependent changes in neutrophil abundance and state composition, together with neutrophil subsets enriched...

Skeletal muscle aging is increasingly recognized as a failure of tissue-level coordination rather than a consequence of isolated defects in individual cell types. Recent advances in single-cell, spatial, and multimodal omics have revealed that aging remodels the abundance, functional states, and interactions of muscle-resident populations, shifting the tissue from a regenerative niche toward a degenerative niche. In this Review, we summarize current evidence supporting this conceptual transition...

Oligodendrocytes (OLs) are brain cells that make myelin, the insulating sheath that supports nerve signal transmission. Although oligodendrocyte dysfunction is common in the central nervous system (CNS), how these cells respond to injury remains incompletely understood. Here we show, using mouse models and mouse tissue analyses, that OLs respond to demyelinating diseases by increasing the expression and secretion of serine protease inhibitor clade A member 3N (SERPINA3N). This transition of...

Algal-bacterial interactions regulate the production and fate of marine particulate organic carbon (POC), yet their capacity to generate long-lived carbon sinks remains unclear. Using a two-year, nutrient-self-sustaining co-culture of Synechococcus and its mutualistic microbiota, we demonstrate that sustained algal-bacterial interactions promote the progressive accumulation of recalcitrant POC. Continuous release of algal-derived organic substrates, coupled with repeated microbial enzymatic...

Chronic stress-induced osteoporosis is a prevalent yet therapeutically challenging condition, with sympathetic overactivation as a key contributor. The dominant pathological mediator and strategies for its precise, non-invasive modulation remain unclear. Here, we identify sympathetic neuropeptide Y as a critical driver of this pathology. Using an unpredictable chronic mild stress model in male mice, we show that neuropeptide Y directly induces cellular senescence in bone marrow adipocytes,...

Aging paradoxically leads to both a decline in skeletal muscle mitochondrial function and a shift in muscle composition that favors fibers rich in mitochondria. Yet the biological rationale and mechanism underlying this phenomenon remain largely unknown. Here we show that synthesis of the mitochondrial membrane lipid, cardiolipin, causally links mitochondrial dysfunction to fiber-type adaptations in aging mouse and human skeletal muscle. By mimicking the aging decline of skeletal muscle...

Extracellular vesicles (EVs) have been proposed to be mediators of the health-promoting effects of exercise throughout the body, but how EVs communicate these beneficial signals to recipient cells remains unknown. Here we interrogated these mechanisms using articular cartilage as a model. Network propagation of EV microRNA perturbations on a cartilage-specific network identified microRNA-29 as an exercise-responsive regulator of cellular aging. Consistent with this prediction, a 3-month aerobic...

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Evidence suggests that age-associated differences in body composition-bone/muscle/adipose tissue-are nonlinear, but their timing, sex-specific features, and relation to osteosarcopenic adiposity (OSA) phenotype remain poorly defined. OSA is characterized by the coexistence of osteopenia/osteoporosis, sarcopenia, and excess or redistributed adiposity. We examined sex- and age-specific patterns and inflection points for bone, muscle, fat, and intramuscular adipose tissue (IMAT) in cross-sectional...

Circumventricular organs (CVOs) are small brain regions lacking a blood-brain barrier, giving neurons direct access to blood-borne signals, yet how these microenvironments shape the origin and phenotype of local macrophages remains unclear. Using multi-omics, we characterized the immune landscape of two CVOs, the area postrema (AP) and median eminence (ME), revealing brain-border-like environments with a unique macrophage compartment. CVO microglia showed a distinct, heterogeneous phenotype,...

AMP-activated protein kinase (AMPK) is a key evolutionarily conserved sensor of energy homeostasis and plays a central role in metabolic health and disease. AMPK has also been implicated in ageing; however, most in vivo drug studies rely on the use of indirect activators, such as metformin, which have complex modes-of-action, therefore making conclusions on the specific role of AMPK more challenging. Here, we demonstrate that direct activation of AMPK with the compound 991 extends lifespan in...

Cellular senescence and chronic low-grade inflammation occupy a central, mechanistically coupled position among the hallmarks of aging. Natural killer (NK) cells decline in per-cell cytotoxicity with age, and lower NK cell cytotoxicity has been associated with higher cancer incidence and infection-related mortality in older adults. NK cells are also endogenous effectors of senescent-cell clearance, engaging stress-induced NKG2D and DNAM-1 ligands and depending on perforin-mediated cytolysis....

Large-scale functional connectivity gradients provide a compact description of cortical organization, capturing hierarchical transitions from unimodal sensory systems to transmodal association cortex. Although these gradients have become a central framework for studying macroscale brain organization, it remains unclear whether they systematically map onto regional cortical biology. Here we show that functional gradient position robustly predicts cortical thickness and regional glucose...

Tauopathies, including Alzheimer's disease, are age-related neurodegenerative disorders characterized by abnormal phosphorylation and buildup of microtubule-associated protein tau. Gene expression dysregulation is a key molecular feature of tauopathies, but how aging and disease interact to disrupt crucial transcriptional regulators and pathways remains largely unknown. Here, we examined how pathological tau affects gene expression programs in age-related neurodegenerative disease using a...

CONCLUSION: The prevalence of pain is relatively high among older people in Mexico. Targeted intervention measures should be taken to improve awareness of the risk factors and the prevention of pain.

Age-related megakaryocyte (MK) dysfunction disrupts platelet production and may increase thrombotic risk, but whether coenzyme Q10 (CoQ10) restores MK homeostasis through autophagy remains unclear. Male C57BL/6J mice aged 1, 9, 15, 19, 21, or 23 months received CoQ10 for 12 weeks. Bone marrow MK proliferation, CD41/CD61 expression, DNA polyploidy, autophagy-associated proteins, and platelet phenotypes were evaluated. H(2)O(2)-induced senescent MEG-01 cells were used for pharmacological...