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As Earth's magnetic field weakens, space radiation begins to pose a significant threat to the health of not only space travelers, but the world's population. Space radiation, comprising high-energy and high-charge ions, creates distinct clusters of DNA damage and dense macromolecular damage that result in the accumulation of senescent cells (SnCs) known to play a critical role in promoting multimorbidity. Here, we demonstrate that human fibroblasts exposed to different forms of space radiation...

Many cellular functions rely on multiprotein complexes and their stoichiometric assembly. Reducing the levels of individual complex components can perturb this process and induce corrective stress responses. In addition to local outcomes, cellular stress in one tissue can induce long-distance responses in other tissues. Here, we used muscle-targeted RNAi to examine the systemic stress responses induced by muscle-specific genetic perturbation of four distinct multiprotein complexes: the...

Plasma biomarkers of Alzheimer's disease and related dementias (ADRD) are associated with the risk of dementia. However, the extent to which they could reflect cognitive ageing, and whether this is consistent across factors known to influence biomarkers (e.g. sex and chronic kidney disease) and in different populations, is unknown. Data were from a diverse community-dwelling cohort of older individuals without dementia in Australia (n = 11,930) and the US (n = 1,181). Global cognition, verbal...

The cerebellum, essential for motor coordination and increasingly recognized for its role in cognition, is typically considered more resilient to aging and largely spared from hallmark Alzheimer's disease (AD) pathology. However, transcriptomic analyses across fifteen mouse brain regions revealed that the cerebellum undergoes some of the earliest and most pronounced age-related changes. To investigate cerebellar aging, we applied single-nucleus RNA sequencing (RNA-seq), microglial bulk RNA-seq,...

The end replication problem refers to incomplete replication of parental DNA at telomeres, a process whose molecular depiction is hampered by the complex nature of telomere ends. Here, we recapitulate this process using a synthetic de novo telomere in Saccharomyces cerevisiae and delineate distinct molecular fates of telomere ends in vivo. We show that the lagging-strand telomeres carry a ∼10 nt 3' overhang, while the leading-strand telomeres have a Yku-protected blunt end, a feature that is...

The cerebellum, essential for motor coordination and increasingly recognized for its role in cognition, is typically considered more resilient to aging and largely spared from hallmark Alzheimer's disease (AD) pathology. However, transcriptomic analyses across fifteen mouse brain regions revealed that the cerebellum undergoes some of the earliest and most pronounced age-related changes. To investigate cerebellar aging, we applied single-nucleus RNA sequencing (RNA-seq), microglial bulk RNA-seq,...

Aging or injury to the joints can lead to cartilage degeneration and osteoarthritis (OA), for which there are limited effective treatments. We found that expression of 15-hydroxy prostaglandin dehydrogenase (15-PGDH) is increased in the articular cartilage of aged or injured mice. Both systemic and local inhibition of 15-PGDH with a small molecule inhibitor (PGDHi) led to regeneration of articular cartilage and reduction in OA-associated pain. Using single cell RNA-sequencing and multiplexed...

CONCLUSIONS: The study highlighted the social and financial obstacles hindering the use of ICOPE Monitor and more broadly, the implementation of frailty screening by primary care practitioners.

CONCLUSION: Prolonged MFB-ICSS treatment mitigates cognitive deficits, modulates circulating levels of miRNA-495 and miR-146a, restores hippocampal NRF2 levels, and preserves corpus callosum integrity in the SAD rat model by STZ injection. These findings highlight the therapeutic potential of MFB-ICSS as a non-pharmacological intervention in AD. Furthermore, this study confirms NRF2 as a target of miR-495 in the context of AD.

Studies in laboratory organisms typically minimize all environmental and genetic variation other than the intervention of interest. In aging studies, these highly controlled conditions have yielded profound insights into aging. But even within isogenic cohorts of lab animals in controlled environments, we observe substantial variation in lifespan. Here we exploited the climbing behavior of Drosophila to study variation in mortality among isogenic populations in a controlled environment. We show...

Human umbilical cord blood (HUCB) exhibits distinct characteristics compared to adult blood, offering significant potential for medical applications, particularly in antiaging therapies. However, the metabolic profile of HUCB relative to adult blood remains poorly understood. Moreover, the specific metabolites within HUCB that confer antiaging properties have yet to be identified. Here, we conducted an untargeted metabolomic analysis comparing cord plasma and adult plasma. Our results reveal a...

Science, Volume 390, Issue 6776, November 2025.

Science, Volume 390, Issue 6776, November 2025.

Science, Volume 390, Issue 6776, November 2025.

Science, Volume 390, Issue 6776, November 2025.

Science, Volume 390, Issue 6776, November 2025.

Science, Volume 390, Issue 6776, November 2025.

Science, Volume 390, Issue 6776, November 2025.

Science, Volume 390, Issue 6776, November 2025.

Science, Volume 390, Issue 6776, November 2025.