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Transcription factors control cell identity and function in health, disease and aging. Here the authors identify age-associated changes of transcriptional regulatory networks in single cells, revealing cell-type and tissue-type-independent patterns in key pathways, including circadian rhythm, antigen processing, collagen processing and inflammation.
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.
Epigenetic clocks can measure biological aging, but the relationship between epigenetic age and other hallmarks of aging is incompletely understood. Here the authors show that epigenetic age is associated with nutrient sensing, mitochondria activity and stem cell depletion but distinct from cellular senescence, telomere attrition and genomic instability.
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.
This study shows that body mass indexes (BMIs) in the overweight or mild obesity range are associated with a decreased risk of mortality in the oldest old in China, supporting the notion that optimal BMIs are age dependent and challenging national and international guidelines on healthy BMI.
The authors used PET imaging to stage individuals according to the Braak neuropathological system for Alzheimer’s disease. PET stage was associated with biomarker and cognitive changes, highlighting the potential to stage Alzheimer’s disease in living people.
Using single-cell and spatial transcriptomics, the authors identified several aging-associated and oxidized phosphatidylcholine-associated changes in microglia in the spinal cord, including an increase in osteopontin that contributed to neurodegeneration and neuroinflammation.
This study investigated trajectories of depressive symptoms associated with several health conditions using a sample of over 19,000 older adults. The presence of depressive symptoms was associated with poor health prognosis and increased mortality.
Luo et al. report a single-cell landscape of human blood from newborn to frailty. Comprehensive profiling uncovers frailty-specific immune cells and gene expression signatures useful for formulating a clinically relevant screen for unhealthy aging.
The authors find extensive remodeling of the gut microbiome and blood metabolome in extremely long-lived individuals (94–105 years old) compared to their children (50–79 years old) and report distinct generation-specific and cross-generational associations with genetic and socioeconomic factors.
The authors used limited proteolysis–mass spectrometry to assess changes in protein structures in mouse CSF with aging. They identified changes in proteins that correlated with cognition and Alzheimer’s disease in humans, including Cd5l/AIM and 14-3-3 proteins.
The authors show that pink1-mutant flies display intestinal dysfunction and that suppression of Relish, an innate immune response mediator, in the gut rescues mitochondrial dysfunction and cell death in the brain.
Apolipoprotein E (APOE) is a lipoprotein particle component and is genetically linked to human longevity and Alzheimer’s disease; however, the mechanisms that link APOE and aging are incompletely understood. Here, Zhao et al. show that APOE drives cellular senescence in aged human mesenchymal progenitor cells by destabilizing heterochromatin.
Immune function decreases with age, leading to increased risk of infectious disease. The authors show that N-glycan branching increases with age in females more than in males as a result of a sex-dimorphic increase in N-acetylglucosamine and interleukin-7 signaling. Reversing elevated branching reduced infection severity in aged female mice.
The authors find that higher adherence to a healthful plant-based diet is associated with a decreased risk of mortality among older adults in China, whereas unhealthful plant-based dietary patterns are associated with increased mortality risk.
In vivo partial reprogramming by expression of Oct4, Sox2, Klf4 and c-Myc has been shown to have rejuvenating effects in a mouse model of premature aging. Here, the authors report that longer-term partial reprogramming regimens are safe and effective in delaying age-related changes in physiologically aged mice.
In a cerebral amyloid angiopathy rat model, the authors show that spinal fluid moves more rapidly but partly bypasses the brain, thereby reducing and delaying waste removal via the glymphatic and lymphatic systems.