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CREB-regulated transcriptional coactivators (CRTCs) have an important role in modulating transcription in a context-dependent manner. Here the authors dissect the role of CRTC-1 in worm lifespan and show that the CRTC-1 transcriptional domain ensures longevity under specific histone marks.
Change in intercellular communication is an important but poorly characterized hallmark of aging. Here the authors provide a bioinformatics tool to infer changes in cell–cell signaling and an atlas of age-related communication changes in 23 mouse tissues.
Hong, Li and colleagues unveil a pivotal role of TET2 in heterochromatin relocalization, aberrant upregulation of endogenous retroviruses and overactivated innate immune response in hematopoietic stem and progenitor cells during aging.
Advanced age is a primary risk factor for female infertility due to declining oocyte quantity and quality. Here Yu Zhang et al. report that supplementation with spermidine rejuvenates the quality of oocytes from aged mice at least in part by enhancing mitophagy and mitochondrial function.
Unlike animals, plants prevent pathological polyQ aggregation through chloroplast proteostasis. Expression of the chloroplast protein SSP in human cell and nematode models prevents disease-related protein aggregation and neurodegeneration.
Ye et al. characterize the cardioprotective effect of SIRT2 in primates and reveal an important role for the SIRT2–STAT3–CDKN2B regulatory axis in primate cardiac aging, improving understanding of the epigenetic mechanism governing cardiac aging.
Ferrari-Souza et al. show that the APOEε4 allele potentiates the deleterious effects of Aβ on the longitudinal accumulation of tau tangles in neocortical brain regions, via tau phosphorylation, which coincides with brain atrophy and clinical decline.
A single-cell transcriptomic analysis by Lau et al. reveals a homeostatic–chemotactic–phagocytic state transition in microglia upon IL-33 stimulation, identifying VCAM1 as a key regulator of microglial chemotaxis by sensing Aβ plaque-associated ApoE.
Pereira, Kumar et al. identify cerebrospinal fluid DOPA decarboxylase as a promising biomarker for Parkinsonian disorders that may be used for early preclinical detection of Parkinsonian disorders as well as determining the risk of conversion to Lewy body disease.
Lamin A/C protects alveolar macrophages against nuclear envelope rupture and DNA damage, but it erodes during aging. Lack of lamin A/C leads to senescence and an aging signature, resulting in vulnerability to influenza virus and lung cancer growth.
Li et al. provide a transcriptional and epigenetic characterization of microglia in aging mice brain by developing a three-round depletion–repopulation (3xDR) model to study aged microglia in non-aged brain, giving insights into the molecular mechanism underlying microglia aging.
Anerillas et al. provide a strategy to eliminate senescent cells that leverages on their secretory needs. Inhibiting YAP–TEAD triggers endoplasmic reticulum stress that eliminates senescent cells from several tissues, improving age-related fibrosis.
Urolithin A (UA) is a gut microbiome-derived metabolite that has been therapeutically explored in aging-related diseases and exerts its benefits in part through effects on mitochondria. Here Girotra, Chiang and colleagues show that UA administration boosts mitochondrial recycling in hematopoietic stem cells and reverses aging features in both the hematopoietic and immune systems.
Using multimodal MRI to delineate noradrenergic and dopaminergic nuclei in aging, Dahl et al. found differential associations with episodic and working memory, helping to disentangle the role of the neurotransmitter systems in age-related memory loss.
Risk stratification based on plasma p-tau217 can substantially reduce the need for invasive or expensive testing when screening for Aβ positivity in patients with cognitive impairment, offering a cost-effective strategy to support an Alzheimer’s disease diagnosis.
The intestinal barrier has an important role in organismal homeostasis; however, the mechanisms that mediate intestinal epithelial aging are incompletely understood. Here, Zhang et al. show that RAB-10 functionality is impaired in aging worms, affecting endocytic recycling and, thus, contributing to the age-related deterioration of adherens junctions.
The authors found that klotho, a longevity and cognition-enhancing factor, can increase the levels of multiple platelet factors in plasma, including PF4. PF4 treatment, which permeated the brain, in turn, enhanced cognition in young and old mice.
The authors report that a change to lysosome morphology, from vesicular to tubular form, supports lifespan extension upon dietary restriction and promotes heightened autophagy and healthy aging when stimulated artificially in well-fed animals.
This study identifies and characterizes evolutionarily conserved cytosine methylation patterns related to age across mammals and establishes pan-mammalian epigenetic clocks.
Using a multivariate genome-wide association study approach, the authors identified 52 genetic variants associated with aging-related traits, many of which are promising cardiometabolic targets that could promote healthy aging and inform future interventions.