Aging & Longevity

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.

CONCLUSION: Health policies developed by the Ministry of Health that take into account the factors associated with healthcare access among older adults are crucial to improving service usage in this sociodemographic. This study presents empirical evidence that can help the Ministry of Health build effective access initiatives for older adults. In this sense, health policies that focus on criteria such as health status and health literacy may help to reduce obstacles to healthcare access and...

Locomotor skills arise early in life and are maintained throughout an animal's lifespan, yet how this continuity is achieved despite major neural remodeling remains unclear. Using Drosophila, which undergoes complete metamorphosis, we show that the activity of embryonically established dopaminergic neurons (DANs) is essential for locomotion across all developmental stages and adulthood. Through stage-specific behavioral assays, optogenetics, in vivo brain imaging, and fluorescent neuronal...

Autophagy is a catabolic process that degrades cytoplasmic materials and is controlled by nutrient availability and signaling. The plasma membrane-associated pyruvate-solute carrier hermes (hrm) is required for regulation of the mechanistic target of rapamycin (mTOR) signaling and the activation of autophagy during development. Here, we screen for pyruvate-influencing genes that suppress the hrm mutant phenotype. We show that the inhibitory effect of hrm loss on autophagy depends on pyruvate...

CONCLUSIONS: Consumer-reported unmet LTSS needs are frequent, vary greatly across care settings and funding programs, and are associated with poorer QoL-related outcomes; highlighting substantial system-level gaps in the fragmented LTSS landscape and the need for coordinated investments and structural reforms to better meet the needs of individuals relying on these services.

Immune function across development, tissue repair, aging, and disease depends not only on signaling pathways but also on epigenetic architectures that determine whether coordinated transcriptional programs can be accessed and resolved. Increasing evidence indicates that epigenetic gene networks regulate the accessibility and reversibility of semi-stable immune states, shaping plastic, homeostatic, reparative, and degenerative configurations. We propose the concept of epigenetic transition...

The relation between cognitive impairment and skeletal muscle mass or physical exercise has been broadly discussed. However, the underlying molecular features have not been systemically investigated. Essential amino acids are the key factors for skeletal muscle mass. In the current study, we investigated the abundance of metabolites in the serum of ~ 1500 participants in various cognitive status from multiple centers. Our study revealed a positive correlation between serum level of essential AA...

CONCLUSION: Higher SES was associated with higher QOL. Older age and widowhood were also associated with lower QOL. Thus, enhancing financial support, expanding social services, and prioritizing the socioeconomically disadvantaged and widowed elderly may contribute to promoting equitable and healthy aging.

CONCLUSIONS: Artificial intelligence holds significant promise for mitigating the global geriatric healthcare crisis exacerbated by demographic aging and nursing shortages. However, realizing its full potential requires a coordinated, multi-stakeholder approach to overcome the entrenched systemic, human, and social obstacles. The proposed roadmaps provide an actionable framework that may facilitate the development of artificial intelligence systems that are more efficient, equitable, and...

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CONCLUSION: These findings identify gaze fixation as a key determinant of increased spin-turn use during turning in older adults, whereby constraining gaze to the near walking surface alters visual information available for step planning and promotes maladaptive turning strategy selection.