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Using light to optogenetically power mitochondria, this study shows that opposing the age-related decline in mitochondrial membrane potential leads to increased healthspan and lifespan in Caenorhabditiselegans. This result points to mitochondrial charge as a fundamental regulator of biological aging.
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.
Single-cell transcriptomic data from a neurogenic region of the mouse brain were used to build aging clocks for specific neural cell types. These clocks showed that heterochronic parabiosis and exercise lead to distinct transcriptomic rejuvenation patterns across cell types.
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.
The authors found that, across tissues and in multiple datasets, aging is accompanied by a length-associated transcriptome imbalance. In most cases, a decrease in the relative abundance of long transcripts was observed and could be reversed by interventions targeting aging.
Mavrikaki et al. show that severe COVID-19 is associated with molecular signatures of aging and low cognitive performance in the human frontal cortex; and emphasize the value of neurological follow-up in recovered individuals.
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.
The authors show that higher concentrations of disease-associated microglial activation stage 2 (DAM2) markers are associated with reduced tau accumulation and slower cognitive decline in nondemented individuals at risk for developing Alzheimer’s disease, suggesting that microglial activation delays disease progression.
The authors analyze microbiome profiles from several public repositories to identify the higher-level indices that best reflect the abundance and ranking of disease-associated and health-associated gut microbes and that may help identify targets for therapeutic modulation.
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.
This study identifies CSF proteins specifically dysregulated along the AD continuum that reflect the multifactorial nature of disease progression. Some of these CSF proteins were used to build biomarker panels with high diagnostic accuracies.
This study found that cerebral small vessel disease was associated with relatively increased glycolysis in the normal-appearing white matter around lesions. Furthermore, lesions tend to develop in white matter that is less glycolytic in healthy humans.
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.
The prevalence and consequences of vision impairment are increasing due to population growth and aging. This study finds that in India, one in three older adults has distance visual impairment or is blind, which may impact not only how they see the world, but also their overall health and well-being.
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.
COVID-19 vaccines protect against infection, hospitalization and death in older adults, but their effectiveness is lower in this age group compared to young adults. Here, Palacios-Pedrero et al. show that age-dependent signs of immunosenescence in B and T cells in older adults correlate with poor immunological outcomes after mRNA COVID-19 vaccination but not after natural SARS-CoV-2 infection.
The intestinal microbiome has an important role in health and disease; however, the long-term effects of lifestyle choices on microbiome alterations are incompletely understood. Here, based on extensive lifestyle and medical data collected over 26 years, Si et al. demonstrate that long-term life history can predict current enterotype in older adults.