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This study shows that intermittent fasting (IF) protects against Alzheimer’s disease in a transgenic mouse model. The authors demonstrate that altered metabolism through remodeling of the gut microbiota mediates the beneficial effects of IF regimen.
Genetic inactivation of the plant homeodomain 6 gene (Phf6) counteracts transcriptional and epigenetic aging programs in the hematopoietic system and can reverse the decline of hematopoietic stem cell function associated with age.
Immune system dysfunction has been implicated in the development of dementias, but its causal role remains unknown. Providing converging results from different lines of human research, this study by Lindbohm et al. suggests that autoimmunity may be a modifiable component in diseases causing dementia.
A metagenomic study of gut, oral and skin microbiota describes a pattern of microbial dysbiosis in more frail institutionalized older adults and identifies the skin as the major reservoir of pathogenicity.
Splicing dysfunction has been observed in Alzheimer’s disease but it remains unclear whether splicing defects have a causal role. Here the authors generate a mouse model with perturbed U1 snRNP activity, recapitulating RNA splicing defects, neuron hyperexcitability, neurodegeneration and synergy with the amyloid cascade when crossed with 5xFAD mice.
Skin thickness and bone density decrease with age; however, the interactions between skin and bone during aging are unclear. Here the authors show that cystatin-A is a skin-derived protein that decreases with age and causes age-related bone loss. Further, topical application of calcipotriol stimulates cystatin-A production in the skin and alleviates bone loss.
In this multi-omics study, the authors identified C1q-dependent synapse elimination by both astrocytes and microglia in Alzheimer’s mouse models. While astrocytes preferentially removed excitatory synapses, microglia preferred inhibitory synapses.
RNA splicing has a role in aging and longevity, but the mechanisms involved are incompletely understood. Here the authors show that mRNA splicing components, RNP-6 and RBM-39, act in concert to regulate intron retention, inhibit mTORC1 signaling and prolong life in Caenorhabditis elegans.
Sexual interactions with males shorten the lifespan of the opposite sex in several species, including Caenorhabditis elegans, but the mechanisms are not fully understood. Here the authors use transcriptomic profiling in C.elegans to systematically identify the genetic pathways involved in male-induced demise, which include upregulation of a conserved ion channel that regulates fat metabolism.
A key challenge for repurposing the licensed drug rapamycin for geroprotection is to avoid side effects from chronic dosing regimens. The authors show in model organisms that a brief administration of the drug early in adulthood has long-lasting beneficial effects that are similar to lifelong treatment.
Somatic mutations accumulate with age; however, the role they have in cardiac aging is unclear. Here Choudhury et al. describe the somatic mutation landscape of human heart muscle cells by single-cell whole-genome sequencing and report mutational signatures indicative of increased oxidative DNA damage and failed repair.
A new population of dysfunctional astrocytes in the aging mouse hippocampus called autophagy-dysregulated astrocytes (APDAs) show impaired protein homeostasis and defective regulation of synapse formation and elimination and appear early in a mouse model of Alzheimer’s disease.
Measuring the rate of aging holds potential for capturing heterogeneity in aging. Here, the authors use longitudinal trajectories of aging phenotypes in the Baltimore Longitudinal Study of Aging and create a longitudinal phenotypic score that is associated with accelerated decline in health and physical and cognitive function.
This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4+ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4+ female individuals.
Senescent cells accumulate with age and contribute to the functional decline of many tissues; however, their role in skeletal muscle is not well understood. Here the authors comprehensively assess cellular senescence in skeletal muscle of young and old mice and detail senescence features in subpopulations of p16+ fibroadipogenic progenitors and p21+ myofibers.
This study shows that during the first wave of SARS-CoV-2 infection in England, residents of long-term care facilities who survived infection developed a robust and stable immunity against the virus that did not negatively impact responses to other seasonal viruses.
This study shows that the cellular pathway that removes dysfunctional mitochondria, mitophagy, becomes impaired in the aged fly brain. Inducing mitophagy in the aging brain prolongs health and lifespan, while slowing both muscle aging and gut aging.
The authors developed a deep learning-based model to estimate the brain age gap based on metabolic and structural imaging data in cognitively normal individuals and in patients with dementia. An older brain age was associated with Alzheimer’s disease biomarkers and was predictive of future cognitive decline.
The authors show that FOXM1 transcription factor transgene induction in Hutchison–Gilford progeria and naturally aged mice significantly extends their lifespan via restoring the loss of Foxm1 function with age that contributes to the aging phenotypes.
Change in sleep patterns is an important feature of the aging process. This study shows that sleep duration is nonlinearly associated with mental health and cognition measures in the 38- to 73-year-old population, with underlying brain and genetic mechanisms.