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Xu and colleagues used partial OSKM reprogramming in aged mice to drive cell-type proportions of the subventricular zone to more youthful levels, which equates to qualified rejuvenation of a neurogenic niche that is defined, in part, by restoration of neuroblast levels.
Epidemiological studies reveal a correlation between hearing loss and the development and progression of Alzheimer’s disease (AD), but the underlying causal mechanisms remain unclear. A study now provides experimental evidence that hearing loss can promote AD via the growth differentiation factor 1 (GDF1) pathway, which may aid in developing potential AD therapeutic strategies.
The extracellular matrix is an essential component of the tumor microenvironment and affects cancer progression. Weeraratna and colleagues have now uncovered that age-related reductions in the level of hyaluronan and proteoglycan link protein 1 (HAPLN1) stimulate neoangiogenesis and compromise the vascular integrity of intratumoral blood vessels. These biological modifications converge to fuel distant melanoma metastasis.
Suda and colleagues explore the enduring consequences of plasma membrane injury in budding yeast and mammalian cells. Their findings highlight that membrane damage induces irreversible cell-cycle arrest and premature cellular senescence, whereas upregulation of plasma membrane repair suppresses them.
Amor and colleagues previously developed chimeric antigen receptor (CAR) T cells that can target and eliminate senescent cells. The utility of these senolytic CAR T cells is now expanded to show that they can combat age-related metabolic dysfunction, and that they can be used prophylactically and have effects that persist for months, thus opening the door to the development of long-term senolytic approaches.
Ying et al. integrate Mendelian randomization into epigenetic clock making and pioneer a strategy to develop aging biomarkers with stronger causal ties to healthspan. They distinguish signs of aging-related molecular damage from responses to it that might signal resilience.
Oleson et al. tackle the enduring question of the extent to which transient events during development shape our outcomes by studying the effects of early-life exposure to oxidative stress. They find that a cascade of changes initiated by the epigenetic-modifier COMPASS complex manifests in rearrangements in lipid metabolism in adulthood, which confers broad protection against amyloid-induced proteotoxicity.
Two recent studies discover a scaling law of mammalian lifespans: the speed at which DNA methylation drifts from a youthful state strongly associates with maximum lifespan.
Targeting tau in addition to amyloid-β could be the next phase of disease modification in Alzheimer’s disease. The TANGO trial of gosuranemab, which binds the tau N terminus, affected neither clinical outcomes nor brain levels of aggregated tau. The results highlight the importance and challenge of reducing aggregated tau.
Epigenome deregulation is considered a hallmark of aging; however, the function of the alteration of DNA methylation in aged tissues is a long-standing question. Hong and colleagues reveal the mechanism and consequences of DNA methylation loss at heterochromatin regions in aged hematopoietic stem cells.
Female fecundity decreases one to two decades before the menopausal transition. A study by Zhang et al. now identifies aging-related decline of the polyamine spermidine as a crucial bottleneck for oocyte quality. Supplementation with spermidine rejuvenates oocytes in vitro and in vivo, and leads to improved fertility of middle-aged female mice.
Human aging is associated with increased rates of many cardiac diseases and tissue remodeling. However, disentangling the mechanisms that underlie normal heart aging from disease processes is challenging. A study now addresses this gap by investigating healthy primate cardiac aging and provides evidence that SIRT2 signaling may regulate cardioprotective effects.
A recent publication in Nature Aging suggests that DOPA decarboxylase may serve as an emerging biomarker that can identify neurodegenerative disorders that are characterized by dopaminergic cell loss. Here we discuss how this finding can assist clinicians and researchers in the differential diagnosis of individuals who present with parkinsonism or cognitive decline.
Intestinal barrier dysfunction is a hallmark of aging. Zhang and colleagues examine the replenishment of adherens junctions in the intestine of aged Caenorhabditis elegans and discover the role of the SDPN-1–RAB-10 axis in the dysregulated endocytic recycling, offering new insights into the age-dependent impairment of the intestinal barrier.
Lysosomes are small vesicles in which cellular constituents are enzymatically degraded. Villalobos and colleagues now show that in Caenorhabditis elegans a shift in lysosome morphology from a vesicular to a tubular shape is critical for the lifespan extension triggered by calorie restriction. Moreover, tubular lysosomes form even in well-fed descendants of calorically restricted parents for up to four generations.
Han et al. provide a substantial contribution to our limited comprehension of the mechanisms of aging in adipose tissue. They show that, with age, increased levels of adipose CRTC2 decrease the breakdown of branched-chain amino acids and activate mTORC1. This in turn leads to increased levels of senescence-associated secretory phenotype factors, which promotes senescence and adipose dysfunction.
Neuronal aging is highly associated with misfolded protein aggregates that predispose to neurodegeneration, but the cellular factors that are involved in removing misfolded proteins are yet to be identified. In this issue of Nature Aging, Li and colleagues identified LONRF2 as an important player in protecting aging neurons against the accumulation of protein aggregates.
Aging increases vulnerability to respiratory viral infections, including by SARS-CoV-2. Delval et al. established a causal role for age-related pre-existing senescent cells in the severity of COVID-19 symptoms in an aging hamster model. Selective depletion of senescent cells using senolytic agents mitigated the risk of severe COVID-19 symptoms linked to aging.
Warde and colleagues demonstrate sex-specific differences in senescence in the adrenal glands of aged mice, with males eliciting a more robust, protective myeloid response that is associated with protection from adrenal cancer.
Li and colleagues address the effect of regulatory T (Treg) cells on the aging process and the role of long non-coding RNAs in Treg cell function. They show that a Treg cell-specific and age-induced long non-coding RNA, Altre, protects the aging liver from age-related apoptosis and metabolic abnormalities.
