Frontiers in aging最新文献

Introduction: Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β (TGF-β) superfamily, has been implicated in aging and muscle homeostasis. However, its clinical relevance and mechanistic role in age-related sarcopenia remain incompletely defined.

Methods: Circulating GDF11 levels were quantified in 159 participants stratified by age (<60 vs. ≥60 years) and sarcopenia status. Propensity score matching (PSM) and multivariable logistic regression analyses were applied to identify factors independently associated with sarcopenia. Mendelian randomization (MR) and mediation analyses were conducted to explore potential causal relationships and indirect pathways linking physical activity, circulating GDF11, and sarcopenia. Bioinformatic analyses integrated skeletal muscle transcriptomic datasets and protein-protein interaction (PPI) networks. Mechanistically, differentiated C2C12 myotubes were treated with recombinant GDF11 (rGDF11), followed by assessment of canonical SMAD signaling and muscle atrophy-related markers, including phosphorylated SMAD3 (immunoblotting) and the E3 ubiquitin ligases Atrogin-1 and MuRF1 at both protein (immunoblotting) and transcript (RT-qPCR) levels.

Results: Circulating GDF11 concentrations were significantly higher in older adults than in younger individuals and were further elevated in participants with sarcopenia, both before and after PSM. Multivariable logistic regression identified circulating GDF11 as an independent risk factor for sarcopenia. MR analysis supported a causal protective effect of physical activity on sarcopenia-related traits, while mediation analysis indicated that circulating GDF11 partially mediated this association. Transcriptomic analyses demonstrated that GDF11 mRNA expression in skeletal muscle remained stable regardless of sarcopenia or exercise status, suggesting that elevated circulating GDF11 is unlikely to originate from skeletal muscle. PPI network analysis highlighted enrichment of activin receptor (ACVR)-SMAD signaling pathways. Consistent with these predictions, rGDF11 treatment activated SMAD3 phosphorylation and induced a dose-dependent upregulation of Atrogin-1 and MuRF1 at both the protein and mRNA levels in C2C12 myotubes, supporting activation of a pro-atrophic ubiquitin-proteasome program.

Conclusion: Circulating GDF11 is elevated in individuals with sarcopenia and appears to partially mediate the protective effects of physical activity. Together with functional evidence of activation of catabolic signaling pathways, these findings support a contributory role of circulating GDF11 in age-related muscle loss.

Background: Sleep disturbances are common in people with dementia and nightly prescribed psychotropic drugs, such as sedatives or antidepressants, can increase risks such as injury, inactivity, and behavioral symptoms. Treatment decisions currently rely on periodic, proxy-rated questionnaires that may miss important daily fluctuations in sleep and activity. We explore whether sensing technologies provide insights into distinct differences in sleep characteristics and activity levels in nursing home residents with dementia who are prescribed nightly psychotropic drugs for sleep disturbances.

Methods: Forty-seven participants were recruited from four nursing homes in Bergen, Norway, and stratified according to prescribed nightly psychotropic drug use for sleep disturbance: 1) none, 2) medications with short half-lives, 3) medications with long half-lives. Garmin Vivoactive5 and Venu3, Vital Things Somnofy sleep monitor, and traditional questionnaires (Physical Self Maintenance Scale and Neuropsychiatric Inventory-Nursing Home version) were used for data collection. Digital metrics included Euclidean Norm Minus One (ENMO; day/night/24-h), Sleep Regulatory Index (SRI), Sleep Efficiency (SE), Total Sleep Time (TST), Sleep Fragmentation Index (SFI), and no presence (time out of bed).

Results: Thirty participants (73-100 years old) were included for analysis. Groups taking psychotropic medications were awake for longer periods (WASO: chi² = 8.7, p = 0.01) and had poorer sleep regularity (SRI: chi² = 20.6, p = 0.0001). Participants taking psychotropic drugs had less physical activity (day/night/24-h ENMO), with greatest differences between those on medications with a long half-life (day: chi² = 9.48, p = 0.009; night: chi² = 12.83, p = 0.002; 24-h: chi² = 8.23, p = 0.02) and those not on nightly psychotropic medications.

Conclusion: The digital biomarkers collected using the selected sensing technologies offered nuanced information regarding sleep behaviors and physical activity levels, providing detailed distinction between the groups. Sensing technologies may be a promising companion to the currently used proxy-rated assessment tools for sleep disturbance and physical activity levels for people with dementia residing in nursing homes.

Fanconi anemia (FA) is a rare genetic disorder characterized by genomic instability, bone marrow failure, physical abnormalities, and increased cancer susceptibility. Growing evidence suggests that. FA may represent a progeroid syndrome, displaying features of accelerated aging at the cellular and molecular levels. This review examines the cellular and molecular characteristics of FA in the context of the established hallmarks of aging, supporting the hypothesis that FA constitutes a premature aging disorder. The hallmarks of aging, classified as primary, antagonistic, and integrative, are highly interconnected and mutually influential. FA cells exhibit primary hallmarks such as; genomic instability, telomere attrition, epigenetic alterations, and dysregulated autophagy. Antagonistic hallmarks, including cellular senescence, mitochondrial dysfunction, and altered; nutrient sensing, are also evident. Integrative hallmarks, such as stem cell exhaustion, altered; intercellular communication, chronic inflammation, and dysbiosis, arise as downstream consequences of the accumulated primary and antagonistic damage. The presence of these hallmarks, together with the early onset of clinical manifestations such as bone marrow failure, cancer, and premature menopause, strongly supports the notion that FA involves accelerated aging. Although patients with FA lacks the overt physical features typical of other progeroid syndromes, its clinical, cellular, and molecular abnormalities demonstrate a strong association with age-related decline, making FA a valuable model of premature aging. Despite limited experimental evidence directly demonstrating accelerated aging, this review highlights the molecular mechanisms linking FA and aging and identifies understudied areas that warrant further investigation.

Ovarian aging is increasingly recognized as a dynamic and modifiable process influenced by oxidative stress, mitochondrial dysfunction, and chronic inflammation. This review outlines the mechanisms by which environmental and lifestyle factors, such as smoking, high-fat diets, endocrine-disrupting chemicals, and micro- and nanoplastics (MNPs), contribute to accelerated ovarian decline and premature reproductive senescence. The distinction between physiological aging and pathological processes such as "inflamm-aging" is discussed, with particular attention to redox imbalance and mitochondrial impairment as key drivers of follicular depletion and endocrine dysfunction. Insights from experimental models of premature ovarian insufficiency and polycystic ovary syndrome are summarized to illustrate the role of reactive oxygen species and oxidative damage. Current antioxidant-based strategies aimed at delaying ovarian aging are reviewed, including melatonin, N-acetylcysteine, coenzyme Q10, polyphenols, and vitamins C and E. Particular emphasis is placed on the emerging potential of stem cell-derived extracellular vesicles (EVs) as a novel, cell-free therapeutic approach. Preclinical evidence suggests that EVs can reduce oxidative stress, support mitochondrial function, and restore ovarian physiology. Overall, the review highlights how redox-targeted and EV-based interventions may offer promising avenues to preserve ovarian function and extend reproductive healthspan.

Background: Centenarians, being at the end of their life span, are particularly vulnerable to various health risks. Multiple factors can influence their survival and targeted intervention on these factors may promote healthy aging.

Purpose: This study aims to explore the effect of physical disability and widowhood on the survival of centenarians.

Methods: Based on the China Hainan Centenarian Cohort Study (CHCCS), this study followed 787 centenarians for 7 years. Data were collected using formal designed questionnaire, physical examination and experimental tests. Questionnaire contains information including geographical data, cognitive and physical function. All the participants were followed-up annually. The endpoint of the follow-up was death or the end of the study. Cox regression analysis was conducted to identify survival-related factors, followed by stratified analysis according to their marital status.

Results: Out of the 787 centenarians, only 382 survived after 7 years, resulting in a mortality rate of 51.46%. Multivariate Cox regression analysis showed that activities of daily living (ADL) (for ADL<60 vs. ADL≥90: HR = 1.933, 95% CI: 1.411-2.648, p < 0.001; for 60≤ADL<90 vs. ADL≥90: HR = 1.438, 95% CI: 1.084-1.907, p = 0.012) was significant factors affecting survival. Stratified analysis based on marital status showed that physical disability was an influence factor of survival in widowed (for ADL<60 vs. ADL≥90, HR = 2.020, 95% CI: 1.450-2.814, p < 0.001; for 60≤ADL<90 vs. ADL≥90, HR = 1.493, 95% CI: 1.108-2.011, p = 0.008) centenarians.

Conclusion: Physical disability and widowhood were important predictors of survival among centenarians. Adequate external assistance should be provided to the disabled and widowed centenarians to enhance their quality of life and survival prospects.

Introduction: The accelerated aging of the Mexican population presents an urgent public health challenge, particularly regarding geriatric mental health. While non-pharmacological interventions (NPIs) offer a promising therapeutic avenue, national evidence remains fragmented. This systematic review critically evaluates the efficacy of NPIs implemented in Mexico to improve mental health outcomes among adults aged 60 and older.

Method: Adhering to PRISMA 2020 guidelines and registered in PROSPERO (CRD420251033051), we conducted a comprehensive search across PubMed, Scopus, and the Virtual Health Library (2010-2025). We included randomized controlled trials and quasi-experimental studies, assessing risk of bias via Joanna Briggs Institute tools.

Results: Seven studies (N = 267; mean age 71.9 ± 7.3) met the eligibility criteria. Synthesis of findings revealed distinct efficacy patterns: physical exercise interventions yielded the most robust outcomes, demonstrating large effect sizes for reducing depressive symptoms (ηp² = 0.35) and enhancing resilience (ηp² = 0.46). In contrast, cognitive and reminiscence-based therapies proved highly effective for improving self-esteem (d = -0.89) but showed inconsistent results for mood regulation.

Discussion and conclusion: Current evidence confirms that NPIs-specifically structured physical activity-are potent and scalable tools for promoting geriatric mental health in Mexico. However, the existing literature is limited by heterogeneity and a lack of geographic coverage. To bridge the gap between research and practice, it is imperative that policymakers transition from isolated pilot interventions to the integration of standardized, evidence-based NPIs protocols within the national geriatric care system.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251033051, identifier CRD420251033051.

Introduction: Defects in Calreticulin (Calr) and ER protein 57 (ERp57), two tandem endoplasmic reticulum (ER) resident proteins, are associated with pathologies ranging from protein conformational disorders to impaired immune responses but are not directly linked to aging.

Methods: To address this question, we analyzed Calr and ERp57 protein levels in brain sections and liver tissues from young and old mice. To evaluate the age-related reduction of Calr and ERp57 in vivo and its physiological implications, lifespan and ER-stress assays were conducted using C. elegans strains. Subsequently, transient knockdown and overexpression of Calr and ERp57 were performed in N2a cells, followed by assessments of cell viability, protein aggregation, apoptotic pathways, and epistasis under both basal and stress conditions.

Results: Here, we report that Calr and ERp57 expression is ubiquitously decreased with age in mouse tissues, and RNAi-mediated inhibition of their homologs in C. elegans leads to ER stress-related lifespan shortening. Knockdown of Calr and ERp57 in N2a cells reduces cellular viability by exacerbating protein aggregation, ER stress, and activation of pro-apoptotic pathways. In contrast, overexpression of Calr and/or ERp57 in N2a cells results in a robust increase in stress tolerance, cell viability, and suppression of apoptotic signaling pathways.

Conclusion: Taken together, our findings suggest that the age-related reduction of Calr and ERp57 may serve as a potential pro-aging biomarker, contributing to the disruption of ER homeostasis and affecting cell survival and organismal lifespan.

Introduction: Prior studies indicate sex-specific obesity-frailty interactions, with postmenopausal estrogen decline increasing sarcopenic obesity risk and inflammation in women. This study evaluated circulating cytokines (IL-6, TNF-α), adipokines (adiponectin, resistin), myokines (GDF-15, BDNF, myostatin), health-related biomarkers (IGF-1, IGFBP-3), and physical performance (five-times chair stand, grip strength) in pre-frail and frail older adult women classified as having low appendicular lean mass (LALM), obesity, or obesity plus LALM.

Methods: In this cross-sectional study, community-dwelling women aged ≥65 years from São Paulo, Brazil were screened (July 2022-September 2023); among 280 eligible, 88 met Fried frailty criteria. Body composition was assessed by DXA and participants were categorized as LALM (<20th percentile of residuals, -1.45), obesity (body mass index, BMI ≥30 kg/m²), or both. Generalized Estimating Equations (GEE) with Bonferroni post hoc adjustments, χ², or Fisher's exact tests were adopted. Unadjusted (P¹) and age-adjusted (P²) P-values were reported.

Results: Among 88 frail women (72.7% pre-frail and 27.3% frail), obesity plus LALM showed lower IGFBP-3 and higher GDF-15 vs. LALM (P² = 0.041 and P² = 0.032); obesity had higher resistin vs. LALM (P² = 0.012), replicated in sensitivity analysis frail-only (P² = 0.002), elevated insulin (P² = 0.002) and a trend slower chair stand (P² = 0.055). GDF-15 was related with chair stand time (Pearson r = 0.285, P = 0.006; and multiple regression β = 0.309, P = 0.013).

Conclusion: Among pre-frail and frail older adult women, obesity-with or without low lean mass-was associated with adverse metabolic/inflammatory profiles (higher resistin, GDF-15, insulin; lower IGFBP-3) in full and frail-only analyses, alongside a trend toward slower chair-stand performance. These cross-sectional findings highlight obesity-frailty interactions, warranting prospective validation.