Aging & Longevity

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...

Immunonutrition refers to nutritional interventions that can improve immune function. The nutritional contents used in immunocytes include amino acids, vitamins, minerals, and flavonoids. In this study, we examine the oxi-inflamm-aging theory, which illustrates the antioxidant effects of diet, immune system performance, and life span. According to this theory, if vitamin C is consumed in the early stages of life, it can increase life span. The main objective of this study was to investigate the...

Clinical evidence supports the anti-photoaging efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT), yet its mechanism remains elusive. Paradoxically, ALA-PDT generates reactive oxygen species (ROS), a key mediator of ultraviolet radiation (UVR)-induced photoaging, raising questions about its rejuvenating effects. Here, we employed a multi-omics approach to clarify this paradox. A UVR-induced hairless mouse model of photoaging was treated with ALA-PDT, followed by transcriptomic,...

Telomerase RNA (TERC) is subject to various modifications, yet the implications of these modifications for telomerase biology remain largely unexplored. In this study, we conducted a comprehensive mapping of N6-Methyladenosine (m6A) modifications within TERC RNA and elucidated their regulatory role in telomerase function. Our findings demonstrate that TERC undergoes methylation at adenosine residues A111 and A435 by METTL3. A deficiency in TERC m6A, which is also linked to various human...

Macroautophagy/autophagy protects muscle from proteotoxic stress and maintains tissue homeostasis, yet skeletal muscle relies on it more than most organs. Adult fibers endure constant mechanical strain and require continuous turnover of long-lived proteins, while muscle stem cells (MuSCs) depend on autophagy to remain quiescent, activate after injury, and regenerate effectively. How autophagy is transcriptionally regulated in muscle has been unclear. We identified DEAF1 as a transcriptional...

Aging adipose tissue is a consequence of organismal aging and an "amplifier" that drives systemic metabolic disorders. This review proposes the conceptual framework of the "aging metabolic amplifier", systematically explaining how aging adipose tissue reshapes the microenvironment of distant organs through its secretory profile, thereby linking obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases. The concept of the "aging metabolic amplifier" emphasizes the important role...

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CONCLUSIONS: This study shows grandparental childcare alleviates older migrants' social isolation (as reflected by higher LSNS-6 scores) by enhancing social participation, with settlement intention moderating the link between social participation and social isolation. Notably, temporary residence mentality may strengthen social participation's positive effect, offering new evidence for explaining migrants' "cultural barriers." Future research should examine mediating variables like language...

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The leukodystrophy Pelizaeus-Merzbacher disease (PMD) is caused by myelin protein proteolipid protein gene (PLP1) mutations. PMD is characterized by oligodendrocyte death and CNS hypomyelination; thus, increasing oligodendrocyte survival and enhancing myelination could provide therapeutic benefit. Here, we use the PMD mouse model Jimpy to determine the impact of the integrated stress response (ISR) on the oligodendrocyte response to mutant PLP expression. Male Jimpy animals in which the...

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Real or simulated microgravity induces a senescence-like modification of carotid artery in both human and animal observations, with the mechanisms not fully elucidated. Here, we aim to elucidate the role of sterol regulatory element-binding protein 1 (SREBP1, encoded by Srebf1) mediated lipogenesis in the process. Pharmacological activation of SREBP1 directly triggers senescence-like transformation in vascular smooth muscle cells (VSMC), while silencing Srebf1 exerts an opposite effect....

Difficult-to-treat rheumatoid arthritis (D2T RA) is an emerging challenge in aging populations, where disease persistence and therapeutic failure often reflect not only autoimmune dysregulation but also the cumulative effects of age-related biological changes across multiple organ systems. This review reframes D2T RA through the lens of geroscience, highlighting how immunosenescence, inflammaging, and organ system vulnerability converge to create a treatment-resistant disease phenotype....

BACKGROUND: Plant-based diets are increasingly adopted. Plant-based foods exhibit a lower protein quantity and quality compared to animal-based foods. As such, a fully plant-based, i.e. vegan, diet may be suboptimal for the maintenance of skeletal muscle mass later in life. The primary objectives of this study protocol are therefore: (1) To assess the effect of a 12-week self-composed vegan diet in comparison to an omnivorous diet on thigh muscle volume in community-dwelling older adults; and...

CONCLUSION: Effective fall prevention in Saudi Arabia requires culturally sensitive, system-wide strategies that address both structural constraints and individual-level beliefs. By enhancing interdisciplinary coordination, improving education, and prioritizing patient-centered approaches, healthcare systems can better support safe aging and reduce fall-related risks among older adults.

Cystathionine γ-lyase (CSE), the enzyme responsible for neuronal cysteine and hydrogen sulfide production, is dysregulated in aging and neurodegenerative diseases including Alzheimer's disease and Huntington's disease, both marked by cognitive decline in addition to motor deficits. To determine whether CSE loss directly causes cognitive decline, we genetically ablated CSE in mice. This loss was sufficient to induce oxidative damage, compromise blood-brain barrier integrity, impair neurogenesis...

The bidirectional non-linear communication between blood pressure (BP) and heartbeat is critical to cardiovascular homeostasis, which remains poorly understood, especially under hypertensive conditions. We implemented transfer entropy (TE), an information-theoretic measure of directional coupling, to characterize such bidirectional coupling between BP and heartbeat and its relationships to arterial stiffness and walking performance in older adults. A total of 493 older adults (201 normotensive...

Individuals with knee osteoarthritis (KOA) have skeletal muscle changes around the knee joint including reduced quadricep muscle mass and increased intermuscular adipose tissue (IMAT). We examined the cellular composition and transcriptional profiles using single-nuclei RNA sequencing in IMAT from 6 older women with KOA and knee pain and 5 older women without KOA or knee pain from the Study of Muscle, Mobility and Aging (SOMMA). From the resulting 21,436 nuclei, we identified 6 major cell types...