Aging & Longevity

Cryogenic electron microscopy has revealed endpoint structures of ex vivo amyloid filaments, but how amyloids assemble and evolve in living organisms-and how these transitions affect physiology-remains poorly understood. Here, we map the age-dependent structural landscape of Orb2 amyloid, a synaptic translation regulator required for long-term memory, across the adult lifespan of Drosophila melanogaster. By determining multiple Orb2 amyloid structures, we uncover a dynamic, age-linked...

A growing body of evidence implicates the menopausal transition as a neurobiological inflection point in women's brain aging and Alzheimer's disease (AD) vulnerability. Menopause is a midlife neuroendocrine transition characterized by a decline in sex steroid hormones and widespread systemic effects. The brain is not a passive recipient of ovarian hormones but an active endocrine-sensing organ. Menopause, however, does not act in isolation: the ovarian-brain axis is established embryonically,...

Oxidative stress and lipid peroxidation are increasingly recognized as age-related drivers of neurodegeneration, with Parkinson's disease (PD) representing a condition of heightened vulnerability. Among lipid peroxidation products, reactive aldehydes including 4-hydroxy-2-nonenal, malondialdehyde, acrolein, 4-hydroxy-2-hexenal, and crotonaldehyde have emerged not only as biomarkers of oxidative damage, but also as active mediators of neuronal dysfunction. Owing to their electrophilic nature,...

CONCLUSION: This study provides the first multivariate genomic characterization of vascular ageing using Genomic SEM, uncovering loci newly implicated in vascular ageing, convergent putative causal genes, and cellular substrates that link vascular biology to systemic ageing and may inform precision prevention of age-related vascular disorders.

Cross-modal associative memory impairment is one of the earliest cognitive markers of neurodegenerative disorders and may be particularly sensitive to the detection of Mild Cognitive Impairment (MCI). The Italian Face-Name Association Test (ItFNAT) assesses face-name associative memory through immediate recall (IR), delayed free (DFR), and total recall (DTR), and qualitative indices. This study provides psychometric properties, discriminative capacity, and diagnostic accuracy in older adults. A...

Cells exhibit innate reparative communication, enabling the exchange of bioactive molecules and, in some cases, entire organelles. Harnessing this endogenous process of intercellular organelle transfer represents an emerging therapeutic paradigm for restoring cellular function in diseases driven by organelle dysfunction. Mitochondrial transfer has gained prominence for its ability to restore bioenergetic capacity, mitigate oxidative stress, and rescue metabolic function in cells with impaired...

CONCLUSION: Cognitive advantages observed in women in midlife did not translate into lower dementia risk. Further research incorporating biological, psychosocial and life-course factors, as well as the timing and heterogeneity of underlying disease processes, is needed to better understand sex differences in cognitive ageing and dementia.

The microstructure of cells within the human cerebral cortex varies across the cortical ribbon, where changes in cytoarchitecture and myeloarchitecture are thought to endow each region of the cortex with its unique function. While fine-scale relative to a cell, these changes at the population level impact architectural properties of the cortex measurable in vivo by noninvasive MRI, such as the thickness and myelin content of the cortex. This raises the question of whether or not we can use these...

Aberrant activation of the STING signaling pathway is involved with aging-related inflammation, yet no STING-targeting therapeutics are clinically approved. Here, we identify Omaveloxolone, an FDA-approved drug for Friedreich's ataxia, as a potent STING degrader (DC(50) = 118 nM, D(max) = 98.6%) via high-throughput screening. Omaveloxolone binds non-covalently to the base of the STING ligand-binding domain (LBD) with high affinity (K(D) = 21.4 nM) and exhibits crowbar-like behavior consistent...

During mitotic growth, Saccharomyces cerevisiae cells age by dividing asymmetrically, producing young daughter cells while retaining age-associated damage in the mother cell, which will eventually become senescent. Gametogenesis naturally and fully resets precursor cell lifespan, even for replicatively aged cells. However, the mechanisms responsible for gametogenic rejuvenation have remained mysterious. This is partly due to the existing methods to quantify lifespan resetting in this context,...

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In mammals, oocytes initiate meiosis during fetal development and then enter a prolonged meiotic arrest. During this female-specific long-term arrest, chromosome cohesion mediated by nonrenewable REC8 cohesin gradually deteriorates, predisposing oocytes to age-associated chromosome segregation errors when meiosis resumes for maturation in adulthood. Female-specific factors that counteract this deterioration remain unknown. Here we identify OMC1 as an oocyte-specific chromosomal protein required...

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CONCLUSION: Cognitive frailty is independently associated with a significantly increases elevated risk of hip fractures in older Chinese older adults, highlighting it as a clinically important and modifiable risk factor. These findings underscore the need for integrated screening protocols that simultaneously assess both cognitive and physical frailty in geriatric care settings.

CONCLUSION: This external pilot showed no superiority of CO-OP plus creative dance over CO-OP alone for the prespecified primary outcome (executive function). Preliminary signals for global cognition and dual-task accuracy warrant confirmation in an adequately powered definitive trial with a prespecified, clinically meaningful primary endpoint.

CONCLUSION: Approximately one-third of older adults had problematic-limited / inadequate health literacy. An independent association was observed between limited HL and a higher probability of being physically inactive. However, health literacy was not independently related to smoking. These findings imply that health literacy may be an important factor underlying differences in physical activity engagement among older adults. Community-based strategies integrating health literacy support and...

CONCLUSIONS: We found that although living alone is associated with mortality, adjustment for social and functional factors may attenuate this association. However, specific subgroups with low income, and scarce social relation lead to increased CCV mortality. Further study with a larger sample size is necessary to confirm this finding.

CONCLUSIONS: This multi-cohort integrative study defines the cellular and clonal signatures of latent CMV in humans and identifies GZMK⁺ CD8⁺ T cells and Th1 cells as previously underappreciated components of the CMV response.

CONCLUSIONS: The findings suggest that healthy ageing in this sample was characterized by multidimensional, heterogeneous and interrelated profiles rather than residential status alone. Functional movement quality and environmental engagement were associated with several healthy ageing indicators, but causal mechanisms cannot be inferred. The results should be interpreted as exploratory and hypothesis-generating, warranting confirmation in larger longitudinal and intervention studies.

In this issue of Cell, Grońska-Pęski et al. examine how calorie restriction (CR) affects DNA mutation rates. While CR lowers the accumulation of mutations, this effect does not scale with the degree of lifespan extension. Their work raises important new questions about how CR impacts the causal mechanisms of aging.