Aging & Longevity

Age acceleration, or the difference between biological and chronological age, is a research area of growing interest, particularly in the field of age-related and neurodegenerative disorders, including Alzheimer's disease (AD). First-generation epigenetic clocks that predict chronological age utilising DNA methylation data were the first to derive estimates of age acceleration, which have been associated with several age-related conditions. More recently, second-generation epigenetic clocks that...

Alzheimer's disease (AD) involves early disruptions in brain connectivity, yet how AD risk markers relate to resting-state dynamic functional connectivity (rs-dFC) remains unclear. We examined associations of AD pathology, genetic risk, and blood-based biomarkers (BBMs) of neurodegeneration with local and distant rs-dFC in cognitively normal older adults and explored links with cognitive performance. Baseline data from 86 cognitively normal older adults in the AGUEDA trial (NCT05186090) were...

Telomere length (TL) has been proposed as a marker of appendicular lean mass (ALM) decline; however, longitudinal evidence remains limited. We aimed to investigate the longitudinal association between TL and 6-year trajectories of ALM. This longitudinal study included 185 older adults aged 55-75 years with overweight or obesity and metabolic syndrome at baseline. Baseline TL was assessed using a monochrome multiplex real-time quantitative PCR. ALM from the four limbs was obtained at baseline,...

Immune checkpoint blockade (ICB) shows limited efficacy in pancreatic ductal adenocarcinoma (PDAC). Here, we demonstrate that ICB-induced IFN-γ signaling upregulates H2-T23 on pancreatic tumor cells, which interacts with NKG2A on NK cells to induce NK cell senescence through activation of p38 MAPK and STAT1/3 pathways. This impairs NK cell cytotoxicity and restricts antitumor immunity. Dual blockade of PD-1 and NKG2A effectively prevents NK cell senescence, restores NK cell function, and...

CONCLUSION: SSDH that shape dementia risk and brain resilience, many modifiable at the community and policy levels, remain unevenly collected in Canadian aging and dementia cohorts. Strengthening and harmonizing SSDH measurement is a critical step toward equitable dementia prevention and reducing health disparities.

Spin glasses are magnetic materials exhibiting numerous magnetization patterns, that randomly vary both in real space and in time. To date, it is still not well understood what the nature of these spatiotemporal dynamics is, namely if they are completely random or if there are relevant and correlated length and time scales. Here, we demonstrate dynamic heterogeneity in the aging dynamics of elemental neodymium. We used spin-polarized scanning tunneling microscopy in combination with atomistic...

Posttraumatic stress disorder (PTSD) is associated with increased risk of chronic disease and premature aging, yet underlying molecular mechanisms remain unclear. We performed plasma proteomics (SomaScan; 9404 proteins) and targeted metabolomics (145 metabolites) in 393 World Trade Center responders (232 with PTSD, 161 trauma-exposed controls). A total of 114 proteins and seven metabolites were differentially expressed in PTSD. Top proteins included NCAN, BCAN, NCAM1, and GDF15. Top metabolites...

Anelloviruses dominate the human plasma virome, yet their lifespan dynamics and relationships with the immune system are unclear. We integrated metagenomics with cytokines, HERV-K, and CMV profiling across 405 individuals (0-100 years) and found that prevalence, abundance, and diversity varied non-linearly with age and by sex. Alphatorqueviruses accumulated progressively with age, while betatorqueviruses and gammatorqueviruses displayed biphasic, female-specific patterns. Alphatorquevirus...

Glial cells shape brain development and aging, yet whether distinct glial lineages undergo coordinated lifespan transitions remains unclear. Although microglial aging states and oligodendrocyte vulnerability in neurodegeneration are well described, it remains unclear whether these programs evolve independently or in a temporally related manner. Here, we analyzed Mouse Cell Atlas single-cell RNA-seq data spanning embryogenesis to 24 months. Microglia and oligodendrocytes were the most...

CONCLUSION: This study demonstrated that Seismofit show a moderate-to-strong association with CPET measurements in older adults. Seismofit, however, systematically overestimated V̇O₂-peak. For Seismofit to be integrated into large-scale cohort studies and experimental research, the methodology used for older adults needs further development.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition. Studies of postmortem ASD brain tissue have revealed convergent molecular changes across the cortex. Whether these features are reflected in cell-type-specific epigenetic signatures is unknown. Here, we present a single-cell analysis of DNA methylation (DNAm) coupled with transcriptomics in ASD. Using snmCT-seq, we profiled DNAm and transcript levels from over 60,000 nuclei derived from the prefrontal cortex of 49...

Whether aging arises primarily from the progressive accumulation of molecular damage (error-based theories) or from regulated, development-related processes (programmatic theories) has been debated for more than a century. This question is central to aging research and shapes our conceptual understanding of aging. Although the existence of a dedicated aging program and the evolutionary advantage of aging remains controversial, the possibility that aging confers adaptive benefits at the species...

Cardiac aging is a fundamental contributor to heart failure, arrhythmias, impaired stress tolerance, and reduced cardiovascular resilience in the elderly. While intrinsic myocardial aging has been widely examined, the systemic mechanisms driving age-related cardiac decline are not fully understood. Circulating extracellular vesicles (EVs) have emerged as key mediators of intercellular and inter-organ communication, transferring proteins, lipids, and nucleic acids that modify the phenotypes of...

CONCLUSIONS: Black older adults without caregivers had the worst observed EOL care quality. Caregiver presence was associated with narrower but persistent racial differences, suggesting structural factors that may attenuate the benefits of caregiving for Black older adults. Policy interventions designed to provide culturally responsive support to minority caregivers may help reduce racial disparities in EOL care quality.

NAT10 is the sole eukaryotic acetyltransferase that catalyzes N4-acetylcytidine (ac⁴C) modification of RNA. While dysregulation of NAT10 is associated with cancer and premature aging syndromes, the requirement for its acetyltransferase activity and how NAT10 coordinates catalysis and RNA binding remain poorly understood. Here, we report single particle cryo-electron microscopy structures of eukaryotic (Chaetomium thermophilum) NAT10 in complex with a designer cytidine-CoA cofactor-based ligand...

Frontotemporal dementia (FTD), a neurodegenerative disorder characterized by early-onset cognitive decline, includes two major pathologic types: FTD-Tau and FTD-TDP. Coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) encodes a mitochondrial protein, and the CHCHD10^(V57E) variant is a novel mutation clinically identified in FTD patients. The role of CHCHD10 mutants in the pathogenesis of FTD-TDP has been largely reported. However, whether CHCHD10 variants impact the FTD-tau...

Aging is increasingly viewed as an organism-wide process marked by systemic decline and multimorbidity. This Review frames immunosenescence as a context-dependent mediator, amplifier, or consequence of multi-organ dysfunction, integrating niche-centered mechanisms, bidirectional immune-organ interactions, innate-adaptive remodeling, immune-tissue axes, and multidimensional biomarkers. We also highlight current limitations, including context heterogeneity and unresolved causality, and discuss...

Lipid metabolism is closely related to aging, and its disorders can lead to obesity, insulin resistance, cardiovascular diseases, and various other conditions. The accumulation of lipids caused by increased lipid synthesis is key in the development of obesity, but the molecular mechanisms of increased lipid synthesis remain to be thoroughly studied, especially in the context of aging. In this work, we used in vivo and in vitro models to demonstrate that the long noncoding RNA Lncbate1...

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CONCLUSION: Cumulative heat exposure poses a significant risk to older adults' mental health, but community-based preventive health services can serve as vital institutional adaptation capital to buffer this risk. Prioritizing targeted health education to bridge the knowledge-action gap, alongside continuous health records monitoring in resource-constrained rural and middle regions, offers an equitable strategy for enhancing climate resilience in aging societies.