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The epigenetic mark H3K9me3 is associated with silencing of lineage-inappropriate genes. Here the authors show that some lineage-inappropriate genes are derepressed in senescent cells through physical decompaction of H3K9me3-heterochromatic regions.
Naked mole rat (NMR) is an exceptionally long-lived rodent species that on the phenotypic level seems to evade aging. Here the authors show that NMRs age epigenetically, while epigenetic clocks detect that NMR queens age more slowly than nonbreeding females.
Using a treatment that activates the peripheral immune system in an animal model of amyloidosis, the authors show that monocyte-derived macrophages can modify Alzheimer’s disease progression via a TREM2-independent mechanism.
This study shows that age-related cognitive decline is alleviated by heterochronic microbiota transplantation in mice and that δ-valerobetaine, a microbiota-derived metabolite that increases with age in both mice and humans, alters neuronal and cognitive processes.
The authors link neuronal expression of telomerase reverse transcriptase to amyloid pathology and cognitive dysfunction in preclinical models of Alzheimer’s disease.
With aging, the immune system undergoes severe changes that impact health in numerous ways. For a comprehensive, translational analysis of these alterations, Krishnarajah et al. here provide profiling of immune cell populations across 12 tissues from young and old mice.
The authors developed a vaccine against a membrane-bound seno-antigen called GPNMB and show that it can be used as a new senolytic approach. The vaccine led to improvements of several age-related phenotypes and prolonged the lifespan of a progeroid mouse model.
Using a new computational approach to identify senescent cells from single-cell transcriptomic data, the authors find that most senescent cells in the human brain are excitatory neurons with elevated CDKN2D/p19 expression, which often display Alzheimer’s disease-associated tau pathology.
Epigenetic clocks emerged as crucial biomarkers of the aging process, but their use has so far been limited to bulk samples. Trapp et al. unveil a new statistical framework that enables epigenetic age profiling at single-cell resolution.
Using an in silico network-based discovery approach, the authors identified sildenafil as a repurposable drug for Alzheimer’s disease. Analyzing insurance claims data from over 7 million individuals, they found that sildenafil usage was associated with a reduced risk of Alzheimer’s disease diagnosis.
Circulating factors play an important role in tissue aging. Here, the authors show that serum EV subpopulations and cargoes remodel with age and that EVs from young mouse serum rejuvenate aged skeletal muscle.
A longitudinal analysis of the mental health impacts of COVID-19 found that over 43% of middle-aged and older adults showed depressive symptoms that increased over time, with loneliness and pandemic stressors being the main predictors.
This study shows that dietary supplementation with B. adolescentis increases the activity of the catalase enzyme and improves the healthspan and lifespan in multiple animal models. Deletion of the catalase enzyme in worms abolished the beneficial effects of the bacterium.
The authors demonstrate that release of peroxidated lipids from mouse neurons following ablation of the small GTPase ARF1 leads to activation of a neurotoxic microglial NLRP3 pathway and show that ARF1 is reduced in human brain tissue from patients with neurodegenerative diseases.
The authors found that deleting an ovary-rich gene called Bin2 improved fertility and oocyte quality in mice. Inhibiting BIN2 with a cell-penetrating peptide improved ovarian function in aging and in chemotherapy-treated mice.
A brain-imaging study in humans demonstrates that older age brain network decline varies in relation to an individual’s education and predicts future dementia severity beyond other markers of Alzheimer’s disease-related genetic risk and pathology.
Integrative single-cell RNA sequencing and immunological profiling reveal that older adults have reduced antigen-specific cellular and humoral responses accompanied by increased cytokine storm and myeloid cell recruiting factors in response to acute SARS-CoV-2 infection.
The authors found that the Alzheimer’s disease-linked APOEε4 allele may prime microglia towards a phagocytic and pro-inflammatory state in the normal aging brain, even before Alzheimer’s amyloid plaques and neurofibrillary tangles develop.
Through computational drug repurposing, Taubes et al. identified bumetanide as a potential drug for APOE4-related Alzheimer’s disease (AD). The effectiveness of bumetanide was validated in AD mouse models and via real-world health record databases.
Cutler et al. found that age predicted individuals’ likelihood to engage in prosocial behaviors such as social distancing during COVID-19 and charitable donations. Older adults across the world were more willing to help but also demonstrated stronger in-group preferences, donating less to international charities.