Aging & Longevity

Population aging is accompanied by a rising burden of metabolic disorders, including obesity, type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular complications. Aging is also associated with broad remodeling of the immune system, characterized by reduced protective capacity together with persistent low-grade inflammatory activity, commonly discussed in terms of immunosenescence and inflammaging. In this narrative review, informed by a...

Insulin-like growth factor-1 (IGF-1) plays a crucial role in brain health and cognitive function, with levels varying across APOE genotypes, a major risk factor for Alzheimer's disease. Here, cross-lagged path modeling was used to examine longitudinal associations between IGF-1 levels, cognitive performance, and sociodemographic factors across APOE genotypes in 1247 older adults from the Rancho Bernardo Study of Healthy Aging. Distinct association patterns emerged across genotypes. Both IGF-1...

Blood pressure, muscle function and central adiposity are routinely measurable but are usually examined as separate risk domains. We analysed harmonised data from the China Health and Retirement Longitudinal Study (CHARLS), the English Longitudinal Study of Ageing (ELSA) and the Health and Retirement Study (HRS) to test whether a rule-based vascular-muscle-adiposity adverse-count phenotype was associated with incident stroke in middle-aged and older adults. The baseline analytic cohort included...

CONCLUSION: BZBS improved skeletal muscle mass and function, trabecular bone microarchitecture, and bone mechanical properties in female Ercc1^(+/-) mice and reduced the skeletal muscle expression of proteins associated with atrophy and senescence. These improvements may be associated with increased whole-body energy metabolism and spontaneous locomotor activity, as well as lower circulating levels of myostatin and FSH and higher levels of E2. These findings provide preclinical support for...

SUMOylation is a reversible post-translational modification increasingly recognized for its role in coordinating cellular responses to metabolic stress during aging. Emerging evidence indicates that it functions beyond a conventional modification, representing an adaptive stress‑responsive regulatory network that integrates metabolic, oxidative, inflammatory, and proteotoxic signals. Rather than acting on isolated pathways, this network finely tunes mitochondrial function, proteostasis, genome...

With advancing age comes declines in physical, cognitive, and cardiovascular function, leading to decreased performance in activities of daily living and eventual loss of independence. Exercise may delay this decline. High-intensity interval training (HIIT) consists of intense activity periods interspersed with bouts of active recovery. Previously, we demonstrated that HIIT preserved physical function in male mice across the lifespan. In the current work, we extend our prior investigations to...

Candidate biomarkers of biologic aging include p16^(INK4a) (p16) expression in peripheral blood T cells, a marker of cellular senescence, and whole-blood DNA methylation (DNAm) clocks, markers of epigenetic aging. Both have been associated with age-accelerating conditions, including cancer and chemotherapy, but their relationship has been inadequately studied. Biomarkers were evaluated in women with early breast cancer (n = 251) and non-cancer controls (n = 49). T-cell p16 expression and five...

Circulating folate, vitamin B12, and homocysteine reflect one-carbon (1-C) metabolism, a pathway central to methylation and cellular maintenance, but longitudinal evidence linking these biomarkers to biological aging remains limited, particularly in low- and middle-income populations. We examined associations of 1-C biomarkers with clinical biomarker-based Phenotypic Age and DNA methylation-based measures of accelerated biological aging among adults aged ≥ 60 years in the Longitudinal Aging...

CONCLUSIONS: In this multinational cohort, the findings revealed the associations of individual- and country-level factors with healthy working lives, underscoring the necessity for measures aimed at extending healthy working lives to align with country-specific social, economic and employment contexts. Besides, interventions targeting individual modifiable risk factors should be warranted through life-course.

Platinum-based drugs cause mutations and liver aging in children treated for cancer.

Copper and iron are redox-active micronutrients with tightly coupled homeostasis, yet how copper modulates iron-dependent stress responses remains unclear. Using Saccharomyces cerevisiae under nutrient-limited conditions, we uncoupled proliferative growth from long-term survival to dissect metal-dependent adaptation. Copper selectively preserved survival without affecting growth, whereas iron showed similar effects. Iron chelation impaired growth and suppressed electron transport chain gene...

Bioelectrical phase angle is an integrated marker of cellular integrity, fluid distribution, nutritional status, and physiological reserve, but its relationship with objective sensory function in later life remains unclear. This population-based cross-sectional study analyzed adults aged 40 years or older from the 2022-2023 Korea National Health and Nutrition Examination Survey. Whole-body phase angle at 50 kHz was assessed using bioelectrical impedance analysis, and pure-tone audiometry was...

While immunosenescence is increasingly implicated in chronic inflammatory disorders, its precise pathogenic contribution to ulcerative colitis (UC) remains elusive. Here, we identify senescent CD8^(+) T cells as a distinct pathogenic population that exacerbates colitis, demonstrating that systemic senolytic treatment significantly attenuates disease severity. Mechanistically, nicotinamide adenine dinucleotide (NAD^(+)) metabolic dysregulation triggers mitochondrial dysfunction and cytosolic...

Reliable differentiation of Parkinson's disease/Lewy body dementia (PD/LBD) from frontotemporal dementia (FTD) affects treatment strategy and clinical trial eligibility, yet confirmatory biomarker testing remains costly and unevenly available. Whether routine cognitive trajectories can support testing prioritization has not been systematically quantified. We performed a progressive inclusion analysis of 1,129 National Alzheimer's Coordinating Center participants with PD/LBD (n = 385) or FTD (n =...

CONCLUSION: Collectively, our data suggest that high WM performance in midlife depends on the flexible modulation of autonomic and cortical resources, potentially facilitating the attentional mobilization necessary for cognitive coping. These neurophysiological signatures allow clearer distinction between a chronological aging profile and a successful cognitive aging profile.

Sarcopenia, the age-related loss of muscle strength and mass, contributes to adverse health outcomes in older adults. Exercise engages calcium (Ca^(2+))- and redox-dependent signaling pathways that enhance muscle performance and adaptation, whereas aging disrupts Ca^(2+) and redox homeostasis. CaMKII is a key transducer of both signals, raising the possibility that sustained CaMKII signaling becomes maladaptive with aging. Here, we show that CaMKII protein abundance is increased in aged mouse...

With the acceleration of global aging, the relationship between Alzheimer's disease (AD) and the glymphatic system (GS) has become a research hotspot in the field of neuroscience in recent years. Traditionally, the central nervous system was thought to lack a lymphatic system; however, research over the past decade has overturned this view. Studies have revealed the existence of GS and meningeal lymphatic vessels (mLVs) in the brain, which clear metabolic waste (such as amyloid-β and tau...

Mitochondria integrate bioenergetics, redox signalling, calcium handling, biosynthesis, apoptosis, and stress responses. Their contribution to ageing depends less on any single pathway than on the ability to sustain these functions through continuous maintenance, remodelling, and inter-organelle communication. This review proposes mitochondrial homeodynamics as a systems-level framework for that ability, which rests not on static preservation but on three linked capacities. Maintenance...

The limited benefits of high-density lipoprotein (HDL)-targeted therapies have shifted the research focus to HDL quality; some HDL subtypes may be pro-atherogenic and may counteract the potential benefits of HDL therapies. This study investigated the pathological mechanism of H5, a highly electronegative and compositionally abnormal HDL subfraction characterized by impaired cholesterol efflux. We used anion-exchange chromatography to separate HDL into five subfractions (H1-H5) from blood from...

As populations age worldwide, pathological neurodegeneration with subsequent cognitive decline has emerged as a pressing public health challenge. As effective treatments remain limited once neurodegeneration has occurred, prevention and delay of decline onset are crucial. While physical exercise is associated with improved cognition, exercise-specific mechanisms remain unclear. We therefore examined the effects of 12 weeks explosive lower-body resistance training (RT) in community-dwelling older...