GeroScience最新文献

Ferroptosis, an iron-dependent form of regulated cell death, is increasingly recognized as a key contributor to aging-associated skeletal muscle degeneration and dysfunction. However, the interactive effects of aging, sex, and exercise modality on ferroptosis regulatory markers at the histological, protein, and gene expression levels remain poorly understood. Male (n = 23) and female (n = 23) mice aged 7 (young) and 17 (aged) months were assigned to sedentary control, voluntary wheel running, or forced treadmill exercise. Ferroptosis in the quadriceps muscle was assessed using histological markers (e.g., fibrosis, Fe³⁺ accumulation, 4-HNE, MDA), protein-level markers (e.g., GPX4, SLC7A11, p-AMPK, MDA, GSH/GSSG), and gene expression markers (e.g., SLC7A11, GSS, ACSL4, POR). Aging significantly elevated histological indicators of ferroptosis-fibrosis, lipid peroxidation, and iron overload-regardless of sex. At the protein and gene levels, sex-dependent differences were evident: aged females exhibited lower MDA and GSSG levels and upregulation of antioxidant-related genes, compared with aged males. Both exercise interventions modulated ferroptosis markers, with forced exercise exerting more pronounced effects than voluntary exercise. Notably, aged females demonstrated the most substantial reductions in ferroptosis-related markers in response to forced exercise, indicating a significant sex-by-exercise interaction. Aging markedly increases ferroptosis-related changes in skeletal muscle, with partial sex-specific differences at the molecular level. Forced exercise provides more robust regulatory effect against ferroptosis than voluntary exercise, especially in aged females. These findings underscore the therapeutic potential of sex-specific, targeted exercise interventions for mitigating ferroptosis-mediated muscle deterioration during aging.

Systemic inflammation following ischemic stroke is driven by a complex interplay among pro-inflammatory cytokines, immune cell activation, and neurovascular dysfunction. Both aging and obesity significantly amplify this inflammatory response, exacerbating stroke severity and impeding recovery. Aging induces a chronic low-grade inflammatory state-referred to as inflammaging-that heightens vulnerability to stroke-induced brain injury. Similarly, obesity promotes a persistent pro-inflammatory milieu that disrupts metabolic and immune homeostasis, further worsening neurological outcomes. The combined effects of aging and obesity pose a substantial barrier to effective stroke rehabilitation and long-term recovery. To improve post-stroke care, future research should focus on three key areas. First, there is a pressing need for targeted therapies that modulate systemic inflammation with minimal side effects. Anti-inflammatory agents such as minocycline have shown promise in preclinical models, but clinical validation is needed. Second, elucidating the molecular mechanisms linking aging, obesity, and systemic inflammation-such as the roles of adipokines and immune cell phenotypes-may reveal novel therapeutic targets. Finally, personalized treatment strategies that consider individual risk factors like age and obesity are essential to optimize stroke management and rehabilitation. Given the limited efficacy of current stroke treatments, prioritizing prevention by identifying high-risk individuals is critical. Recognizing non-modifiable risk factors can support more intensive intervention on modifiable ones and guide vigilance toward vulnerable populations. Overall, advancing our understanding of systemic inflammation and its modifiers will be key to developing innovative, patient-specific therapies aimed at improving outcomes and quality of life for stroke survivors.

Frailty is increasingly recognized as a major determinant of surgical risk in older adults; however, its prognostic significance in the context of elective neurosurgery remains unclear. This study investigated the prevalence of frailty, the concordance between three validated frailty instruments, and their association with postoperative complications. A prospective cohort study was conducted at a tertiary neurosurgical center from November 2021 to November 2024. Patients aged ≥ 65 years undergoing elective cranial or spinal surgery were included. Preoperative frailty was assessed using the Clinical Frailty Scale (CFS), the Comprehensive Geriatric Assessment Frailty Index (CGA-FI), and the Fried's Frailty Phenotype (FFP) criteria. Postoperative complications-including infectious, cardiovascular, neurological, haemorrhagic events, delirium, and in-hospital death-were systematically recorded. Associations with frailty were examined using multivariable logistic regression adjusted for covariates. Among 181 patients (mean age, 74.1 [SD] 6.1 years), frailty prevalence ranged from 23.8% (CGA-FI) to 44.2% (FFP). Agreement between instruments was variable, with substantial concordance between CFS and CGA-FI (κ = 0.65) and only moderate concordance with FFP. Postoperative complications occurred in 47 (25.9%) patients. Frailty defined by CFS (adjusted odds ratio [aOR], 2.73; 95% CI, 1.05-7.42) and CGA-FI (aOR, 3.78; 95% CI, 1.34-11.1) was independently associated with increased risk of complications. In conclusion, frailty as assessed by the CFS and CGA-FI, is a strong determinant of postoperative risk in older adults undergoing elective neurosurgery. Incorporating frailty assessment into routine neurosurgical pathways may improve perioperative risk stratification and guide clinical decision-making.

A substantial proportion of dementia risk may be attributable to modifiable factors, yet these are often examined in isolation despite their interrelated nature and tendency to co-occur. It remains unclear whether the relationship between modifiable factors and dementia risk is influenced by individual characteristics such as sex and genetic susceptibility. We investigated longitudinal associations between the Lifestyle for Brain health (LIBRA) score and risk of dementia, cognitive performance, and brain structure, and whether relationships differed by sex and APOE ɛ4 carrier status.Participants were aged > 50 years, dementia-free at baseline, 50% female and predominantly (97%) white/Caucasian. The LIBRA score included 11 modifiable factors (e.g., hypertension, obesity, physical inactivity). Magnetic resonance imaging estimated brain volume, domain-specific cognitive composite scores were calculated, and dementia diagnoses were determined based on self-reported and linked healthcare data.Across a mean follow-up of 10.2 years, a higher LIBRA score was associated with greater odds of developing dementia (OR = 1.20, 95% CI 1.18-1.22). This association was stronger in APOE ɛ4 non-carriers compared to ɛ4 carriers. Cross-sectionally, higher LIBRA scores related to poorer cognition, smaller whole-brain gray and white matter volumes, and increased ventricular cerebrospinal fluid (CSF), however, only the association with increased ventricular CSF persisted longitudinally (mean follow-up 3.4 years).Each one-point increase on the LIBRA score was associated with 20% increased odds of developing dementia. These results reinforce the need to target modifiable dementia risk factors and to tailor dementia prevention strategies to individual risk profiles to maximize the impact on brain health.