Frontiers in aging最新文献

Introduction: Growing demand for liver transplantation (LTx) has increased the use of elderly donors. In Argentina, however, data on the clinical impact of donor age on post-transplant outcomes remain limited.

Objective: To evaluate the effect of donor age on clinical, functional, and molecular outcomes after LTx at Hospital Universitario Fundación Favaloro Buenos Aires, Argentina.

Methods: We performed a retrospective cohort study of 494 LTx conducted between 2009 and 2020. Patients were stratified into two age groups: 18-59 years (Younger) and ≥60 years (Elderly). Overall and graft survival (OS and GS) were assessed using Kaplan-Meier and Cox regression analyses adjusted for recipient age, donor age, recipient gender, donor gender, transplant year, MELD score, disease etiology, donor BMI, DRI, CIT, WIT, Total Bilirubin (TBIL) and INR. Early postoperative complications including early allograft dysfunction (EAD) and early renal replacement therapy (RRT) were evaluated. Post-transplant liver function was assessed by routine biochemical tests. Gene expression of pro-inflammatory and senescence markers was quantified by qRT-PCR, and lipofuscin deposition was measured using ImageJ.

Results: After applying exclusion criteria, 267 LTx were included (Younger donors: n = 222; Elderly donors: n = 45). Recipients of elderly donor grafts showed significantly lower OS and GS (p < 0.05). In the multivariable analysis, donor age and TBIL remained independent predictors of GS, whereas donor age, recipient age, and TBIL were associated with OS. In contrast, neither the incidence of EAD nor early RRT differed between recipients of elderly versus young donor grafts. Early postoperative biochemical profiles were also similar between groups, with no significant differences in ALT, AST, ALP, or TBIL levels. Molecular analyses demonstrated that elderly donor livers exhibited significantly higher expressions of IL-1β, IL-6, TNF-α, p21 and CCND1, Elderly donor livers displayed higher baseline lipofuscin accumulation (p < 0.05), consistent with age-associated cellular senescence, and trends toward higher rejection rates.

Conclusion: Donor liver aging, characterized by increased inflammatory and senescence signatures, is associated with reduced patient and graft survival. These findings underscore the clinical relevance of considering donor biological age, beyond chronological age, in organ allocation and selection strategies.

Background: By 2050, the global population of individuals aged 60 years and older is projected to reach two billion, with 80% residing in low- and middle-income countries (LMICs). Africa's older population will triple from 74.4 million in 2020 to 235.1 million in 2050, the fastest growth rate globally. Kenya is slightly ahead of the curve on this trajectory, with the population of approximately 2.74 million of the older people expected to quadruple to 12 million over the same period. The Longitudinal Study of Health and Aging in Kenya (LOSHAK) is designed to advance research on population aging in LMICs by focusing on (a) biomarkers and physiological measures; (b) the impacts of air pollution and climate vulnerability; (c) Alzheimer's disease and related dementias, mental health, disability, caregiving, and psychosocial wellbeing; (d) economic security, including the impact of social welfare; and (e) establish cohorts for long-term study of trajectories of healthy aging and their determinants in a LMIC setting.

Methods: The LOSHAK feasibility and pilot phase was a cross-sectional survey of 203 participants aged 45 years and older. This paper reports on the association between self-reported health and sociodemographic, functional, and objective health measures.

Results: Overall mean age was 63.8 years (SD:11.5) with females accounting for 58.1% (118) of the study population. Based on the wealth index, 111 (54.7%) were classified as poor, with only 75 (36.9%) currently working, with a median income of KShs.11,246.60 (USD 86) over the 3 months preceding the study. Only 32 (15.8%) of respondents reported "very good" self-reported health, while over 80% reported either "somewhat good" 96 (47.3%) or "not good" 75 (36.9%) health status. Multivariable ordinal logistic regression analysis showed that younger age (adjusted odds ratio (aOR): 0.94, 95% CI: 0.91-0.97) and higher subjective wellbeing (aOR: 1.06, 95% CI: 1.02-1.12) were significantly associated with better self-reported health.

Conclusion: This study highlights the importance of considering sociodemographic, subjective wellbeing, and psychosocial factors in improving the health of older adults in Kenya. Including these measures in longitudinal studies of aging and health in Africa in the future is recommended.

Aims: To compare the effectiveness of an 8-week multicomponent exercise program delivered at home with digital support versus conventional in-person hospital exercise sessions in reducing FOF.

Materials and methods: The GAITCARE project is a multicenter quasi-experimental trial in three hospitals. Participants were assigned by hospital to either: (1) VIVIFIL App group-individualized daily home exercise with remote supervision; or (2) In person group-face to face exercise at hospital day-care units. The primary outcome was FOF measured by the Short Falls Efficacy Scale-International (Short FES-I). Secondary outcomes included adherence and app satisfaction.

Results: 127 participants were included (64 in App group, 63 in-person group), aged 70-93 (mean 82.36). FOF (SFES-I) was present in 68.3% of the in-person group and 54.7% of the App group. The 8-week intervention reduced FOF scores in both groups, reaching statistical significance only in the in-person group. However, the App group also showed a clinically relevant reduction (∼20%) despite starting with slightly lower baseline FOF, suggesting potential benefits of remote delivery. The in-person group showed higher adherence at weeks 4, 8, and 12 (follow-up). Baseline physical activity influenced adherence, with sedentary participants showing lower adherence. Digital delivery with remote supervision showed good feasibility and was generally well accepted by participants.

Conclusion: FOF is prevalent in older adults with falls and can be significantly reduced by face-to-face group exercise, which also achieves higher adherence. Enhancements in telematic applications are necessary to improve adherence in digital interventions targeting FOF.

With growing global interest in extending not only lifespan but also healthspan, healthy aging has emerged as a central goal in biomedical research. This review provides an overview of current longevity interventions, including genetic manipulations, dietary restriction, exercise, pharmacological treatments, targeting senescence and cellular reprogramming strategies, as studied in key model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. We examine the limitations and challenges associated with these approaches, particularly their variability across tissues and cell types. Furthermore, we emphasize the critical role of single-cell aging atlas technologies in uncovering cell-type-specific aging patterns and molecular signatures. By integrating single-cell data, we propose that future interventions can be more precisely designed to target aging at the cellular level, thereby enhancing the efficacy and specificity of longevity strategies.

Genetic syndromes of immune dysregulation have opened a door toward understanding mechanisms linking inflammation, premature aging, and normal aging. Here, we discuss new insights into the relationship between DNA damage, premature senescence, and nucleic acid-sensing pathways that detect or regulate DNA damage. First, we review mechanisms by which the DNA exonuclease TREX1 negatively regulates the cytosolic DNA sensor cGAS and its downstream effector STING, and we propose a model of TREX1-mediated DNA damage and cellular senescence that implicates age-related, inducible TREX1 expression in the context of genetic disease and inflamm-aging. Our central thesis is that two TREX1-associated diseases-Aicardi-Goutières syndrome (AGS) and retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S), historically regarded as inflammatory conditions-can serve as models for research into mechanisms of premature aging.

Introduction: Biological age acceleration and disruptions in neurotrophin pathway signaling may significantly contribute to cancer-related cognitive impairment (CRCI) etiology. In this study, we evaluated the relationship of epigenetic age acceleration with cognitive function measures and circulating BDNF levels. Furthermore, we evaluated DNA methylation (DNAm) patterns to explore neurotrophin pathway associations with CRCI symptoms.

Methods: In a longitudinal study, 51 newly diagnosed Adolescent and Young adult cancer patients and 8 age-matched healthy controls provided blood samples for DNAm and BDNF measurements with concurrent clinical assessments (#NCT03476070). We evaluated the relationship of epigenetic ageing with cancer status, circulating BDNF levels, and measured cognitive function. Next, we identified significant differentially methylated positions (DMPs), regions (DMRs), and significantly enriched pathways associated with BDNF and cognitive function outcomes.

Results: PhenoAge and GrimAge demonstrated significant age acceleration relative to non-cancer controls and worsening cognitive function symptoms, with accelerated GrimAge associated with decreasing BDNF levels. DMPs associated with 5 different cognitive function outcomes (FactCog Score, Response, Memory, Executive Function, Multi-Tasking) were mapped to genes within KEGG pathway HSA:04722 (Neurotrophin Signaling Pathway). Key enriched pathways relative to both subjective cognitive function and multiple objective cognitive measurement domains were also enriched with respect to BDNF levels, including Synapse (GO:0045202), Glutamatergic Synapse (GO:0098978), and Neuron Projection (GO:0043005).

Conclusion: Cancer and cancer treatment lead to significant epigenetic age acceleration, which can influence neuronal health and CRCI symptom onset. Furthermore, DNAm patterns corroborate BDNF as a potential biomarker for CRCI and suggest neurotrophin pathways play a meaningful role in CRCI etiology.

Background: Single-cell multi-omics (SCMO) technologies simultaneously profile multiple molecular layers (e.g., DNA, RNA, proteins) within individual cells. Unlike traditional bulk analyses that average signals across thousands of cells, SCMO captures the unique molecular characteristics of each cell, potentially transforming our understanding of disease pathogenesis and clinical management. Despite its promise, SCMO methodologies remain complex and difficult for clinicians to interpret and utilize effectively.

Methods: We conducted a narrative review specifically tailored to clinicians, summarizing key SCMO methodologies, recent discoveries, and their translational relevance for cardiovascular and aging-related diseases. Our goal was to simplify complex SCMO concepts, highlight practical clinical insights, clarify methodological details in accessible terms, and openly discuss barriers currently preventing routine clinical implementation.

Results: SCMO techniques have identified clinically relevant cellular heterogeneity within diseases such as atherosclerosis and heart failure, uncovering subpopulations linked to disease severity and potential therapeutic targets. Notably, SCMO studies revealed specific inflammatory immune subsets in unstable plaques, pathogenic fibroblast populations driving cardiac fibrosis, and distinct immune profiles associated with aging and longevity. Early clinical trials integrating SCMO demonstrate feasibility in oncology and cardiology, and prototype clinical assays (e.g., single-cell "liquid biopsies") are emerging. These advances are yielding predictive biomarkers and guiding personalized and preventive applications.

Conclusion: SCMO is rapidly evolving, offering unprecedented precision in diagnostics and personalized therapeutics by pinpointing disease-driving cells and molecular pathways. However, significant hurdles including high costs, technical complexity, and analytical challenges currently limit immediate clinical application. To the best of our knowledge, as of 2025, FDA authorization for single-cell diagnostics is limited to established technologies like flow cytometry, while next-generation multi-omic platforms remain confined to research use. This manuscript is explicitly designed to help clinicians navigate the complexity of SCMO, providing clear, digestible explanations of its methodologies and emphasizing how these tools might practically benefit patient care. Clinicians should remain cautiously optimistic, viewing SCMO as a complementary, specialized tool. Continued technological and methodological advances suggest SCMO will become increasingly integral to precision medicine.

Background: Recent investigations across both animal models and human cohorts increasingly highlight cellular senescence as a critical pathological process driving the development and progression of diabetic nephropathy (DN). The detrimental impact of senescent cells on DN advancement stems from a range of underlying mechanisms, notably telomere attrition, compromised mitochondrial function, dysregulated autophagy, chronic inflammatory responses, altered mTOR signaling and Sirtuin activity, and the release of pro-coagulant factors. Diabetic kidney disease (DKD) is a common and serious complication in diabetic patients, closely associated with high glucose-induced defects in kidney cells. Currently the clinical treatment of DKD disease is still a challenge. Celastrol, a compound derived from Tripterygium wilfordii, has shown significant therapeutic effects on DKD, but the specific mechanisms remain unclear.

Methods: We established in vitro and in vivo models of DKD using human renal tubular epithelial cells (HK-2) and Sprague-Dawley (SD) rats. The effects of celastrol on glucose-induced oxidative damage to HK-2 cells and kidney injury in DKD rats were observed. The potential mechanisms were investigated through both in vitro and in vivo experiments.

Results: High glucose induced accelerated senescence of HK-2 cells in vitro, and celastrol reversed senescence-associated pathological changes in the cells. Celastrol reduced pro-inflammatory signaling and mitochondrial damage in vitro by inhibiting the phosphorylation of aging- and inflammation-related proteins NF-κB and AKT1. In vivo, celastrol inhibited the phosphorylation of NF-κB and AKT1 in renal tissues, effectively improving renal dysfunction and pathological changes in DKD rats, and reducing disease-related indicators.

Conclusion: Celastrol may be a promising candidate drug for the treatment of DKD. It can treat DKD by reversing the imbalance of the immune-inflammatory system mediated by the AKT/NF-κB/TNF-α signaling during the progression of the disease and may also delay the progression of DKD through its anti-aging effect.

The purpose of this exploratory post hoc analysis was to study the impact of semaglutide on measures of bone health in older adults. Data were collected from a 20-week pilot trial (NCT05786521), which randomized 20 older adults (72.7 ± 4.8 years of age, 50% women, 45% Hispanic) living with prediabetes/diabetes (hemoglobin A1C 5.7%-7.5%) and overweight/obesity [body mass index (BMI): 32.9 ± 4.0 kg/m²] to 1.0 mg/weekly semaglutide + lifestyle counseling (n = 10) or lifestyle counseling alone (n = 10). The total body weight, bone mineral density (BMD), and bone turnover markers (BTMs) [C-terminal telopeptide of type 1 collagen (CTX) and procollagen type I N-propeptide (P1NP)] were measured at baseline and 20 weeks. Twenty-week weight loss was greater in the semaglutide + lifestyle counseling group than in lifestyle counseling alone (-5.3% vs. -0.89%; p < 0.01). No significant differences in whole-body BMD (p = 0.77) or BTMs (CTX: p = 0.56, P1NP: p = 0.78) were observed between groups over time. In this 20-week pilot trial, we did not find evidence to suggest that weight loss achieved with semaglutide was associated with change in BMD or BTMs in older adults. Notably, the observed differences showed consistently lower BMD and higher bone turnover at follow-up in the semaglutide + lifestyle group than in the lifestyle alone. Additional work in this area is warranted to further evaluate the effect of glucagon-like peptide-1 receptor agonist (GLP1Ra) use on skeletal health outcomes in older adults, given the pilot nature of the trial, the small degree of weight loss achieved, and the well-described association between weight loss and fracture risk.