Aging in orbit: The twelve hallmarks as a bidirectional bridge between spaceflight-induced senescence and terrestrial geroscience.

HIV infection may affect uric acid (UA) metabolism, but no large-scale population-based studies have investigated whether and how HIV infection affects incidence of hyperuricemia. Prospective, observational, noninterventional study. We included 1836 people with HIV (PWH) who had normal UA level at baseline assessment and 1836 age-, sex-, and baseline UA level-matched people without HIV (PWoH) from the Comparative HIV and Aging Research in Taizhou (CHART) cohort. Hyperuricemia was defined as a serum UA level ≥7 mg/dl, following Chinese clinical guidelines. Logistic regression models were used to examine the association and potential effect modifiers. A generalized linear model (GLM) and bootstrap method were employed to assess the mediation effect. The three-year cumulative incidence of hyperuricemia was significantly lower in PWH than in PWoH overall [11.6% vs. 16.4%; adjusted odds ratio (aOR) = 0.67; 95% confidence interval (CI): 0.55, 0.82], and significantly lower in male PWH than in male PWoH (13.1% vs. 19.4%; aOR = 0.64, 95% CI: 0.52, 0.79) but comparable between female PWH and female PWoH (6.2% vs. 6.1%, aOR = 0.97, 95% CI: 0.55, 1.72). A significant additive interaction between sex and HIV infection was observed, with a relative excess risk due to interaction (RERI) of -1.18 (95% CI : -2.87, -0.13). Among males, lower BMI and albumin to globulin ratio (AGR) mediated 36% and 12% of the association between HIV infection and lower risk of hyperuricemia, respectively. HIV infection was associated with a lower risk of hyperuricemia in men but not women, partially mediated by lower BMI and AGR, suggesting distinct metabolic and inflammatory profiles in male PWH.

BackgroundAlthough studies have explored tea and coffee in relation to Alzheimer's disease, no century-scale analysis has jointly examined both within a unified primary-evidence framework.ObjectiveThis study maps the structural, thematic, and temporal evolution of coffee and tea research in cognitive aging.MethodsScopus-indexed original English articles (1911-2025) were retrieved using a structured Boolean strategy under PRISMA guidance. Analyses were conducted using Bibliometrix and VOSviewer. Performance metrics, collaboration networks, co-citation mapping, Bradford's Law, co-word clustering, thematic evolution, and overlay visualization were applied to full-period and recent (2021-2025) datasets.ResultsA total of 2873 articles across 1285 sources demonstrated steady annual growth (4.96%) and substantial citation impact (mean 40.17 citations per document). Research productivity was concentrated in high-income countries, led by the United States, United Kingdom, and China, reflecting core-periphery stratification and citation asymmetry. Collaboration networks showed hub dominance with dense transatlantic-Eurasian linkages. Bradford analysis identified a limited core of highly productive journals. Thematic evolution revealed persistent anchoring in Alzheimer's disease, oxidative stress, and neuroprotection, with sustained prominence of coffee, caffeine, tea, and polyphenols. Recent years indicate translational expansion integrating microbiome science and computational methods. Overlay visualization demonstrated temporal stratification, highlighting emerging themes such as gut microbiota and deep learning alongside stable beverage-related cognitive frameworks.ConclusionsCoffee and tea research in cognitive aging has evolved into a mature, mechanistically grounded, and globally stratified field, increasingly integrating translational, microbiome, and computational approaches in dementia-related investigations.

Aging is characterized by progressive physiological decline and age-related pathologies, yet the molecular determinants underlying lineage- and species-specific aging traits remain poorly understood. Although protein-coding regulators have dominated aging research, the contribution of long non-coding RNAs (lncRNAs), particularly primate-specific lncRNAs, has not been systematically explored. Here, through evolutionary screening and cross-species aging-associated analyses, we identified a set of primate-specific lncRNAs (including LINC01021, CTC-575 l10.1, CTA-150C2.13, and RP11-305F18.1, etc.) associated with human aging, and we functionally characterized LINC01021 as a representative candidate to assess their causal involvement. In human cells, LINC01021 promotes cellular senescence, whereas its silencing attenuates senescence-associated phenotypes. Mechanistically, LINC01021 is predominantly located in the nucleus, where it facilitates DAZAP1-dependent destabilization of RBMX mRNA, leading to activation of the P53 pathway and induction of canonical senescence features. At the organismal level, ectopic expression of human LINC01021 in mice contributes to aging-like phenotypes, including increased frailty and impaired motor coordination. Together, these findings implicate primate-specific lncRNAs in lineage-restricted aging and highlight an evolutionarily recent regulatory layer that may modulate aging trajectories.

β2-Microglobulin and the ageing brain.

The Hallmarks of aging: Paradigms and scientific progress.

Over the past decades, numerous studies aimed to discover the fundamental cause of the aging process. Rather than a single root cause, multiple factors were identified, suggesting that aging manifests itself through a progressive degradation of different molecules, cells and in the end, entire systems, directly affecting an individual's health. To address this rapidly growing challenge, various anti-aging strategies have been proposed, among which partial reprogramming has emerged as a promising approach capable of extending both lifespan and healthspan. In this review, we summarize the historical development of aging theories, the effects of established anti-aging strategies, and the evolution of partial reprogramming using Yamanaka factors. We also highlight recent advances in overcoming the efficacy and safety limitations of partial reprogramming, as well as the remaining challenges that must be addressed to fully realize its therapeutic potential.

As the largest and most externally exposed organ, the skin is particularly vulnerable to aging, rendering skin aging a widespread clinical and aesthetic concern. Driven by both intrinsic and extrinsic factors, skin aging is characterized by progressive functional decline and structural remodeling that compromise barrier integrity, disrupt dermal homeostasis, and ultimately diminish quality of life. At the upstream regulatory level, skin aging-associated epigenetic modifications drive epigenetic drift that compromises transcriptional fidelity and primes cells toward senescence. At the cellular level, regulatory mechanisms converge on cellular senescence and profound mitochondrial remodeling. At the microenvironmental level, the failure of senescent cell clearance (immunosenescence) and the emergence of a chronic pro-inflammatory milieu (inflammaging) create a self-reinforcing immune-inflammatory axis. This axis exacerbates cytokine production, extracellular matrix remodeling, and progressive tissue degeneration. We further highlight emerging mechanism-targeted interventions, including epigenetic and mitochondrial modulators, senotherapeutics, biologics, immunotherapies, regenerative and device-based therapies. A deeper understanding of these interconnected molecular mechanisms and targeted therapies may offer a roadmap for future therapeutic innovation and translational research in skin aging.

This correspondence offers a methodological reflection on the cross-sectional study by Darabi and colleagues, which examines loneliness and social support in older Iranian adults with cardiovascular disease. The study addresses an important gap in Middle Eastern aging research. However, the reported positive correlation between loneliness and social support invites closer methodological consideration. We invite readers to consider four methodological aspects: whether shared method variance may have influenced the observed correlation, why subgroup findings do not follow the reported trends, whether the instruments perform similarly in a low-literacy population, and what the cross-sectional design can, and cannot, tell us about directionality. These considerations suggest the observed association might benefit from further investigation with longitudinal designs and objective measures. We hope these reflections support the continued study of social health in aging populations.

The African turquoise killifish Nothobranchius furzeri has emerged as a valuable vertebrate model for ageing research. Despite its increasing use in laboratory studies, systematic welfare monitoring approaches in N. furzeri is still emerging, and only a limited number of structured health-assessment frameworks have been proposed. Here, we present a welfare scoring system designed for daily monitoring of N. furzeri across its entire lifespan under laboratory conditions. Building on established zebrafish welfare frameworks and adapting them to the biological and ethological characteristics of N. furzeri, we identified a set of morphometric, behavioural and clinical parameters, including body condition score, external appearance, food intake, respiratory pattern, swimming activity, tank occupancy and clinical signs. Each parameter was assigned a numerical score ranging from 0 to 3, reflecting increasing degrees of welfare impairment. We further defined standardized intervention criteria, including humane endpoints, to support decision-making in cases of compromised welfare. Importantly, we established five distinct age stages to enable age-specific welfare assessment in two widely used wild-type strains, GRZ/GRZ-AD and MZM04-10. This scoring system provides a practical, reproducible, and easily implementable tool that can be seamlessly integrated into routine husbandry procedures. Its application is expected to promote standardized welfare assessment, improve experimental reproducibility, and enhance animal welfare standards in research using N. furzeri.

Aging, or organismal senescence, is a gradual decline that begins in adulthood, leading to functional loss and an increased risk of disease. Genomic instability and telomere shortening are primary hallmarks associated with aging. Mre11, crucial for DNA damage repair and telomere maintenance, is a potential biomarker of aging. The silkworm, Bombyx mori, is an ideal model for life science research due to its similarities to humans and experimental advantages (well-annotated genome, short life cycle, and appropriate body size). Mre11 is highly conserved across species. In this study, we embarked on establishing the aging silkworm model and evaluated the etiology. Firstly, we constructed Mre11 homozygous mutants by the CRISPR/Cas9 system. Further examination showed that BmMre11 deficiency successfully induced senescence in the fat body. Furthermore, transcriptome and lipidomics analyses indicated that dysregulation of mitochondrial and lipid metabolism is associated with fat body senescence. This work expands our understanding of Mre11's functions in insect metabolism and aging, offering a promising model for fat body aging research.

We conducted a Mendelian randomization (MR) study to examine the associations of mitochondrial DNA copy number (mtDNA-cn) with 27 gastrointestinal diseases (GDs). To investigate the causal relationship between mtDNA-cn and the risk of 27 GDs, a two-sample MR analytic framework was used. A series of quality-control procedures were followed in order to select eligible instrumental variables that were strongly associated with mtDNA-cn. This two-sample MR study employed 2 cohorts of European ancestry with mtDNA-cn genome-wide association study summary statistics: the UK Biobank (395,718 samples) and the combined Cohorts for Heart and Aging Research in Genomic Epidemiology and UK Biobank dataset (465,809 samples). Genetic associations with 27 GDs were obtained from FinnGen and other large consortia. We conducted MR analyses separately in the 2 cohorts, followed by a meta-analysis. The Cochran Q test and MR-Egger intercept test were used to assess heterogeneity, horizontal pleiotropy, and the stability of single-nucleotide polymorphisms in GDs. The results of the discovery cohort showed that mtDNA-cn was significantly associated with ulcerative colitis (UC) after false discovery rate correction, and a suggestive association with an increased risk of diverticular disease of the intestine was noted for genetically predicted mtDNA-cn. However, the validation cohort did not find any causal relationship between mtDNA-cn and 27 GDs. Results from 2 cohorts were combined using the fixed-effect model; in the meta-analysis, the causal associations remained the same as in the discovery cohort. Our findings summarize the role of mtDNA-cn for 27 GDs. Findings may support a causal effect of mtDNA-cn in the development of UC and diverticular disease of the intestine. These findings have implications for mtDNA-cn as a biomarker of UC and diverticular disease in clinical practice.

Why we age - Integrating error, program, and selective pressure.

Review of current research practices in social and structural determinants of health data collection in Canadian longitudinal cohorts of aging and dementia.

The accumulation of mitochondrial DNA (mtDNA) deletion mutants in post-mitotic cells is a hallmark of mammalian ageing and a key contributor to tissue decline in skeletal muscle and neurons. A transcription-coupled replication model predicts that deletions affecting a negative feedback mechanism gain a selective replication advantage, leading to relatively short accumulation times for mutant takeover. However, these accumulation times are experimentally inaccessible since single-cell measurements are destructive. Here, we present a framework to infer such accumulation times from cross-sectional single-cell RNA sequencing (scRNAseq) data, exploiting the fact that mtDNA deletions are also reflected at the transcript level. To establish feasibility, we generated synthetic datasets using two stochastic models of the mitochondrial life cycle and used these as a gold standard. We then applied the Moran process, a stochastic birth-death model, to calculate distributions of accumulation times and to extract key parameters. The Moran model reproduced the distributions obtained from stochastic simulations with high fidelity across different assumptions about mitochondrial regulation. Fitting the model to synthetic data, successfully recovered mutation probability, selection advantage, and the fraction of advantageous mutants. These results establish a methodological framework for quantifying mtDNA mutant dynamics from single-cell transcriptomic data and provide a foundation for analysing large experimental datasets in ageing research.

Despite the findings that older adults in post-industrial countries value sexual vitality and sexual expression more than previous generations, cross-cultural research in positive sexual aging has been very limited. Building on a new (non-normative) process-based concept, the Successful Sexual Aging Model, and its recent three-dimensional operationalization, the current study aimed to provide systematic evidence about cultural differences in positive sexual aging. Using data from four countries - Croatia (n=201), Germany (n=895), Portugal (n=191) and Japan (n=391) - collected from older partnered individuals aged ≥65 years in quota-based national online panels (the Portuguese convenience-based community sample was an exception), we used a novel social network analytic approach to assess similarities and differences in the structure of successful sexual aging (SSA). Although the basic composition of SSA was confirmed across the countries, most structural links connecting the three psychosocial processes (acceptance, adaptation and opportunities) that were proposed to underlie SSA were culture specific. Emerging patterns of differences did not indicate a marked distinctiveness of SSA in Japan, when compared with the European countries. Our findings represent an initial step toward exploring cultural differences in positive sexual aging.

The African turquoise killifish, Nothobranchius furzeri, has emerged as an important vertebrate model for aging research due to its naturally short lifespan and hallmarks of aging. However, these characteristics create challenges for colony management, such as high breeder turnover, rapid generational change, and the risk of inbreeding or unintended selection in closed laboratory populations. Since new individuals cannot be introduced from the wild or purchased from commercial laboratory animal breeders, maintaining genetically stable laboratory stocks requires carefully controlled breeding strategies. Here, we describe an innovative colony management approach termed dynamic population breeding (DPB) and evaluated its performance in two commonly used laboratory lines with different lifespans, GRZ-D and MZCS-08/122. DPB integrates several key principles: the maintenance of overlapping breeding age cohorts, harem-based breeding groups, continuous monitoring of clutch quality and quantity, and the controlled use of embryonic diapause for flexible embryo storage and synchronized hatching. Embryos from multiple breeding groups were pooled, stored in diapause stage II, and hatched at defined time points to generate new cohorts while avoiding sibling-only populations. Using this approach, we systematically analyzed reproductive performance, embryo quality, hatching success, and survival in laboratory populations. Fertilization rates and clutch sizes remained within stable ranges across the reproductive period, although an age-dependent decline in fertilization efficiency was observed in both lines. Quality control at the clutch level allowed early identification and exclusion of low-performing breeding groups. Importantly, implementation of DPB reduced variability between cohorts and improved early-life survival of offspring, particularly during the first weeks after hatching. Overall, DPB provides a practical framework for maintaining stable and robust killifish colonies while minimizing unintended selection and inbreeding. By integrating diapause biology with structured breeding management, this strategy enhances reproducibility and sustainability of N. furzeri populations used in aging research.

Identifying biomarkers that identify vulnerability to age-related cognitive decline is a major priority in aging research. Adropin, a circulating peptide that regulates metabolic and vascular homeostasis, has been associated with cognitive performance in humans, but its relevance across species has remained unclear. Here we report low plasma adropin concentrations associate with poor decision-making in aged rhesus macaques subject to an increasing food choice test paradigm. Animals with higher adropin levels exhibited faster improvement in reaction time and reductions of variability in reaction time, whereas intrinsic performance on simple tasks was preserved. These associations were most apparent under conditions requiring adaptation to novelty or stress, suggesting that adropin may signal cognitive resilience rather than baseline executive capacity. The findings parallel mechanistic data from rodent models linking adropin signaling to mitochondrial function, resistance to oxidative stress, and hippocampal-dependent learning. Together, these results support measurements of circulating adropin as a conserved, translational biomarker of cognitive aging and a potential therapeutic target.

ABSTRACT Increasing life expectancies and growing diversity among adults create a need for scholars who understand intersecting identities in aging. NIA-funded Advancing Diversity in Aging Research (ADAR) programs aim to diversify this workforce; however, additional strategies are needed to expand undergraduate engagement in gerontological research. We integrated an ADAR-informed research poster project into a non-ADAR undergraduate course. Students used publicly available data to examine aging-related health disparities among populations with intersecting identities and presented their findings as professional posters. Students who selected the poster option earned higher grades and reported satisfaction with the project; however, these differences should be interpreted cautiously, as assignment selection was not randomized. This approach offers a practical model for engaging undergraduates in gerontological research and may support broader participation in the field.

The AVOID Frailty framework, developed by the Canadian Frailty Network, promotes five evidence-based behaviors to reduce frailty risk in older adults: physical activity, vaccination, medication optimization, social interaction, and nutrition. Although widely adopted, its deficit-based framing may limit engagement and appeal. This commentary proposes a positively framed alternative, the THRIVE Strategy for Lifelong Wellness, which retains the core behavioral focus of AVOID while adding a sixth pillar, engaging the mind, to reflect evidence on cognitive and emotional well-being in aging. We further recommend shifting from the language of frailty prevention and healthy aging towards lifelong wellness, a more inclusive and empowering concept. Drawing on health communication theory and aging research, we argue that gain-framed messages are more motivating, less stigmatizing, and relevant across the life course. By emphasizing thriving rather than avoiding decline, the THRIVE strategy offers a holistic and potentially more effective framework for promoting sustained well-being across adulthood and later life.