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Moderate cold temperature extends lifespan, but the mechanisms involved are not fully understood. Here, the authors show that moderate cold temperature eliminates aggregation-prone proteins through PSME3-activated proteasomes in both C. elegans and human cells.
Sen et al. show that, during human cellular senescence and mouse tissue aging, chromatin alterations promote the initiation of transcription from non-canonical sites and lead to deterioration of cellular health.
By showing that the immune modulator MANF is induced after muscle injury in young but not aged mice and is essential for regenerative success, this study reveals a new link between immune dysfunction and regenerative decline in muscle aging.
Xiao et al. report a weaker adaptive immune response in older adults after inactivated SARS-CoV-2 vaccination compared to young adult controls, identifying altered immune cell function and decreased antigen-specific receptor repertoire diversity as potential underlying mechanisms.
APOE4 is produced by neurons under stress, but the role of neuronal APOE4 in Alzheimer’s disease pathogenesis is still unclear. Here the authors report that selective removal of neuronal APOE4 in tauopathy mice mitigates many prominent Alzheimer’s disease-related pathologies.
Dobyns et al. use latent variable modeling to derive a single, putative measure of resilience that buffered the effects of the hallmark Alzheimer’s disease pathologies, tau and amyloid, on episodic memory and non-memory decline, respectively.
Moigneu, Abdellaoui and colleagues show that GDF11 attenuates depression-like behavior and improves memory in aged mice through neuronal autophagy and mTOR. Serum levels of GDF11 are inversely associated with depression in patients.
Zhang et al. demonstrate that targeting BUBR1, a nuclear mitotic spindle assembly checkpoint protein, alleviates premature aging phenotypes of progeria in mice via disrupting its nuclear mislocalization induced by progerin interaction.
Older people have suboptimal responses to primary series vaccines, which can place them at risk for adverse coronavirus disease 2019 outcomes. Here the authors show that booster vaccines provide a substantial increase in antibody levels in the short term but that there is significant waning 100 d after booster shots.
Impaired CD4+ T cell responses in older adults correlate with weaker humoral and cellular immunity as well as reduced systemic reactogenicity following mRNA coronavirus disease 2019 vaccination, thus highlighting the impact of T cell aging on vaccine effectiveness.
Baez-Lugo et al. show that increased functional brain connectivity between default mode network and amygdala in resting state after high emotional events is associated to higher anxiety, rumination and negative thoughts in older adults.
This study identifies a new germline-to-soma aging signal tuned by mating in Caenorhabditiselegans. The authors find that germline piRNAs influence longevity and somatic maintenance by transcriptionally regulating germline-to-soma Hedgehog signaling.
Xie et al. identify activation of the innate immune cGAS-STING pathway in human Alzheimer’s disease (AD) brain and 5×FAD mouse model of AD. Suppressing the cGAS-STING pathway is shown as a target to alleviate AD-associated pathogenesis in mice.
Kabir et al. show that aged bone marrow induces smooth muscle cell (SMC) polyclonality in atherosclerosis. Decreased TET2 levels in aged myeloid cells lead to silenced integrin β3, resulting in increased TNFα signaling and the expansion of multiple SMC progenitors.
The authors show that liver sinusoidal endothelial cell (LSEC) senescence promotes steatosis by reprogramming liver endothelial zonation and inhibiting C-kit, a type III receptor tyrosine kinase. Infusing C-kit-expressing LSECs in aged or diet-induced NASH mice counteracts senescence and steatosis.
Nuclear morphology changes with aging, but the role of these changes and the underlying mechanisms are not fully understood. The authors find that the nuclear envelope anchor protein ANC-1 in worms, and its counterpart nesprin-1 and nesprin-2 in mammals, promotes the degradation of nuclear components to limit nucleolar size and function in a soma longevity and germline immortality mechanism.
Kirkland et al. identify conserved age-dependent nuclear remodeling in Drosophila cardiomyocytes, dependent on declining Lamin C. They show that Lamin C loss induces reversible heart dysfunction by repressing myogenic transcription factors.
The authors show that sphingolipids, a class of fat molecules, accumulate in skeletal muscle during aging. They demonstrate that reducing sphingolipids improves age-related fitness in mice by enhancing the myogenic response of muscle and present genetic evidence that these findings may also translate to humans.
Martínez Corrales et al. show that the activation of the conserved pro-longevity transcription factor FOXO solely in youth promotes subsequent health and survival in female fruit flies, via chromatin remodeling and induction of Xbp1.
Understanding sex differential responses to geroprotective interventions is key to developing personalized longevity treatments. Here, Regan, Lu et al. show that the sexual identity of intestinal enterocytes regulates autophagy to determine the response to the drug rapamycin.