Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
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.
Liu and colleagues investigate the effects that ovarian aging may have in granulosa cell-to-oocyte communication and demonstrate that oocyte rejuvenation and the extension of reproductive lifespan is possible by increasing lipid metabolism in granulosa cells in mouse.
The mysteries behind immune aging and its related inflammation are being unmasked. Jin et al. reveal that the defective turnover of damaged mitochondria in CD4+ T cells from older individuals results in the exacerbated secretion of mitochondrial DNA, which fuels inflammaging and impairs immune responses.
Epigenetic changes are a driver of senescence and occur during aging. A study in Nature Aging shows how chromatin-mediated loss of transcription fidelity, previously shown in yeast and worms, also occurs in mammalian cells and could constitute a new hallmark of senescence and aging.
The ability of adult neural stem cells to produce new neurons (neurogenesis) declines markedly during aging, but exactly how this occurs is largely unknown. Using sophisticated in vivo imaging, a study in Nature Aging shows that aging affects several steps of neurogenesis — most notably, increasing the death of newborn clones.
Wang Lin and his colleagues explore how aging reprograms spatially unique pathways in liver endothelial cells to cause fibrosis. They find that loss of KIT in liver endothelial cells close to the central vein upregulates the chemokine receptor CXCR4 to stimulate inflammation, enhance fibrosis and increase lipid accumulation in aged liver.
Aging is known to be associated with a decline in memory and mood, but the molecular mechanisms that underlie these changes remain unclear. Moigneu, Abdellaoui and colleagues show that growth differentiation factor 11 reverses deficits in these functions in aged mice, pointing the way towards a novel pro-mnemonic and antidepressant therapeutic target.
Zhang and colleagues demonstrate how the premature aging phenotypes in progeria involve a mitotic spindle-assembly-checkpoint protein, BUBR1. BUBR1 is misanchored to the nuclear membrane by progerin and its mRNA is destabilized in progeria, preventing it from functioning properly.
Aging is known to exacerbate atherosclerosis, but the mechanisms have been largely unknown. A study in Nature Aging reveals a bone-marrow-controlled axis of clonality during atherosclerosis, showing that aged bones drive an inflammatory milieu that promotes smooth muscle polyclonality and the formation of larger lesions.
