Aging & Longevity

Quantifying individual deviations in brain morphology from normative references is useful for understanding neurodiversity and facilitating personalized management of brain health. Here we report Chinese brain normative references using morphological imaging scans of 24,061 healthy volunteers from 105 sites, revealing later peak ages of lifespan neurodevelopmental milestones (1.2-8.9 years) than European/North American populations. We model individual brain deviation scores in 3,932 individuals...

CONCLUSIONS: Current research on MCR management is in its early stages and does not fully align with the integrated, proactive principles of the PHM framework. The evidence base is dominated by risk stratification and preliminary intervention studies, while foundational areas like health literacy and technological monitoring are less developed. Future work could focus on standardizing MCR assessment, addressing key gaps in the underrepresented PHM dimensions, and developing and testing...

Older adults are disproportionately affected by infectious diseases like influenza (flu) due to immune declines and poor vaccine responses. Senolytics have been shown to improve various age-related conditions and positively influence infection outcomes, yet their potential to enhance vaccine responses has not yet been explored. Here, we evaluated the potential of senolytic combination Dasatinib (D) and Quercetin (Q) treatment prior to influenza vaccination to potentiate immune responses in aged...

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human...

Kinship relationships between parents affect offspring fitness. Beyond its effects in heterozygosity or its impact in deleterious alleles that can be reduced to homozygosity and decrease the individuals' fitness, the consequences of parental relatedness in the offspring remain understudied. By leveraging the availability of detailed pedigrees of captive Peromyscus we explored how parental relatedness impacts the methylome and the epigenetic age estimation of the offspring. Global CpG methylation...

On October 22nd, 2025, Brain Aging Symposium took place at Harvard Medical School bringing together leading researchers from academia and partner organizations to discuss recent advances in measuring and monitoring human brain aging trajectories, with a particular focus on Alzheimer's disease (AD). A central theme emerged: achieving "the right treatment for the right person and the right time" through precision medicine approaches. Key advances included the unprecedented validation of...

A key characteristic of senescent and ageing cells is a reduction in number and increase in size of nucleoli. Although a number of pathways have been suggested, the mechanisms underlying this altered nucleolar phenotype, and the downstream consequences, remain poorly understood. The PolI complex component, TIF-IA, has previously been implicated in regulating this characteristic nucleolar phenotype in response to stress. Here we explored the role of TIF-IA in senescence and ageing. We show that...

Periodontitis and smoking are major contributors to oral and systemic health deterioration in aging adults. This study investigated the combined effects of smoking status and periodontitis severity on the subgingival microbiome in 1107 individuals aged 69-72 using shotgun metagenomic sequencing. Smoking was linked to reduced microbial diversity, enrichment of periodontal pathogens, and depletion of health-associated commensals, while increasing periodontitis severity was associated with broader...

The olfactory epithelium (OE) undergoes life-long renewal and regeneration. This process is supported by the globose basal cells (GBC) during the homeostatic state, as well as horizontal basal cells (HBC) during severe damage. Inflamm-aging refers to the low-grade, chronic and progressive state of heightened pro-inflammation associated with aging. However, the impact of inflamm-aging on OE homeostasis, regeneration, and the inflammatory microenvironment is not fully understood. In this study...

Social support has been related to cardiovascular disease (CVD) incidence and mortality in longitudinal cohort analyses, but the biological pathways underpinning this remain underexplored. This exploratory study examined the associations between social support and a wide range of proteomic biomarkers and performed the mediating effect of proteomic biomarkers in the association between social support and CVD and mortality to identify potential biological pathways linking social support to health...

Ovarian somatic cells are essential for reproductive function, but no existing ex vivo models recapitulate the cellular heterogeneity or interactions within this compartment. We engineered an ovarian somatic organoid model by culturing a stroma-enriched fraction of mouse ovaries in scaffold-free agarose micromolds. Self-organized ovarian somatic organoids maintained diverse cell populations, produced extracellular matrix, and secreted hormones. Organoids generated from reproductively old mice...

CONCLUSIONS: BRI is a multifaceted predictor of chronic disease mortality, with associations varying by disease pathophysiology and population characteristics. It offers a pragmatic tool for refining risk stratification in aging populations and challenges one-size-fits-all approaches to obesity management. Future research should investigate dynamic BRI trajectories and interactions with disease-specific biomarkers.

CONCLUSION: This study shows a clear inverted U-shaped relationship between physical activity and cognitive function in older adults with DM. Cognitive benefits do not increase with higher exercise volume and approximately 490 MET-minutes/week appears to be the optimal dose for preserving cognitive function in this population. Additional research is necessary to confirm these findings in future studies using objective, precise measures such as pedometers and accelerometers.

CONCLUSION: Chinese older adults showed inequality in IC, with more pronounced inequality in urban areas. Social activity and age are major contributing factors. Interventions such as promoting social participation, optimizing environmental resources, and implementing tailored urban-rural health policies are recommended to mitigate IC inequality and advance health equity.

Aging is an inevitable consequence for all organisms. According to the mitochondrial free radical theory of aging (MFRTA), reactive oxygen species (ROS), which are predominantly generated in mitochondria, are assumed to play a key role. Calorie restriction (CR) delays aging by improving mitochondrial function; however, the molecular mechanisms underlying the effects of ROS and CR on mitochondria remain poorly understood. Oxidative protein modifications in mitochondrial proteins from the heart...

There is increasing evidence that nutrient composition, even without lowering total calorie intake, can shape lifespan through mechanisms independent of mitochondrial regulation. Brandon and colleagues recently reported that a low-protein, high-carbohydrate (LPHC) diet enriched with non-digestible cellulose, extends lifespan in mice by shifting the liver proteome through altered RNA splicing, a response different from the mitochondrial improvements typically seen with caloric restriction. The...

Against the backdrop of the global trend toward delayed childbearing, elucidating the mechanisms underlying uterine aging has emerged as a critical biomedical priority for addressing age-related implantation failure. Through unbiased global metabolomic profiling of peri-implantation uteri across different ages in mice, we identified nicotinamide adenine dinucleotide (NAD^(+)) depletion as a hallmark metabolic feature of endometrial aging. Single-cell RNA sequencing further revealed an expansion...

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid-beta plaques and neurofibrillary tau tangles in the brain, neuroinflammation, and cognitive impairment. The 3xTg-AD mouse is a commonly used model in AD studies. 3xTg-AD males display inconsistent pathology; therefore, most studies utilize females. An understanding of why sexual dimorphism exists in this model is lacking. In humans, low circulating choline levels are associated with elevated AD pathology, while...

N6-methyladenosine (m6A) methylation, a dynamic and reversible modification of eukaryotic mRNAs, plays critical roles in diverse cellular processes. Although METTL3-mediated m6A deposition has been implicated in cellular senescence, the mechanisms controlling METTL3 stability and activity during senescence remain poorly defined. Here, we demonstrate that both m6A levels and METTL3 protein abundance are significantly reduced in replication-induced and stress-induced senescence models. METTL3...

Previous research examining the contribution of white matter hyperintensities (WMHs) to cognitive decline has focused on overall lesion burden. A new approach, afforded by the Lesion Quantification Toolkit (LQT), measures localized connectivity disruption from WMHs to better estimate their impact on cognition. This methodology shifts the focus from lesion volume to the level of network disruption between brain regions. In this novel study, we applied the LQT approach to healthy aging and linked...