Aging & Longevity

Cardiovascular disease is currently the largest cause of mortality and disability globally, surpassing communicable diseases, and atherosclerosis is the main contributor to this epidemic. Aging is intimately linked to atherosclerosis development and progression, however, the mechanism of aging in atherosclerosis is not well known. To emphasize the significant research on the involvement of senescent cells in atherosclerosis, we begin by outlining compelling evidence that indicates various types...

Age is the primary risk factor for Parkinson's disease (PD), but how aging changes the expression and regulatory landscape of the brain remains unclear. Here we present a single-nuclei multiomic study profiling shared gene expression and chromatin accessibility of young, aged and PD postmortem midbrain samples. Combined multiomic analysis along a pseudopathogenesis trajectory reveals that all glial cell types are affected by age, but microglia and oligodendrocytes are further altered in PD. We...

Non-canonical lipolysis induced by inflammatory cytokines or Toll-like receptor ligands is required for the regulation of inflammation during endotoxemia and sepsis. Canonical lipolysis induced by catecholamines declines during aging due to factors including an expansion of lymphocytes, pro-inflammatory macrophage polarization, and an increase in chronic low-grade inflammation; however, the extent to which the non-canonical pathway of lipolysis is active and impacted by immune cells during aging...

The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor-infiltrating T cells (TILs), hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to...

Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course. As a result, a range of lung-function trajectories exist in the population. Below average trajectories are associated with respiratory, cardiovascular, metabolic, and mental health...

The accumulation of somatic mutations is a driver of cancer and has long been associated with ageing. Due to limitations in quantifying mutation burden with age in non-cancerous tissues, the impact of somatic mutations in other ageing phenotypes is unclear. Recent advances in DNA sequencing technologies have allowed the large-scale quantification of somatic mutations in ageing tissues. These studies have revealed a gradual accumulation of mutations in normal tissues with age as well as a...

The escalating prevalence of neurodegenerative diseases (NDDs) within an aging global population presents a pressing challenge. The multifaceted pathophysiological mechanisms underlying these disorders, including oxidative stress, mitochondrial dysfunction, and neuroinflammation, remain complex and elusive. Among these, the AMPK/SIRT1/PGC-1α pathway emerges as a pivotal network implicated in neuroprotection against these destructive processes. This review sheds light on the potential therapeutic...

Ultraviolet radiation (UVR) is primarily recognized for its detrimental effects such as cancerogenesis, skin aging, eye damage, and autoimmune disorders. With exception of ultraviolet B (UVB) requirement in the production of vitamin D3, the positive role of UVR in modulation of homeostasis is underappreciated. Skin exposure to UVR triggers local responses secondary to the induction of chemical, hormonal, immune, and neural signals that are defined by the chromophores and extent of UVR...

SET-26, HCF-1, and HDA-1 are highly conserved chromatin factors with key roles in development and aging. Here we present mechanistic insights into how these factors regulate gene expression and modulate longevity in C. elegans. We show that SET-26 and HCF-1 cooperate to regulate a common set of genes, and both antagonize the histone deacetylase HDA-1 to limit longevity. HCF-1 localization at chromatin is largely dependent on functional SET-26, whereas SET-26 is only minorly affected by loss of...

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Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1-SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active...

Metabolic reprogramming of stem cells is a targetable pathway to control regeneration. Activation of stem cells results in down-regulation of oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) and turns on glycolysis to provide fuel for proliferation and specific signaling events. How cell type-specific events are regulated is unknown. In this issue of Genes & Development Ciuffoli and colleagues (pp. 151-167) use metabolomic, gene inactivation, and functional approaches to show...

The extrinsic diet and the intrinsic developmental programs are intertwined. Although extensive research has been conducted on how nutrition regulates development, whether and how developmental programs control the timing of nutritional responses remain barely known. Here, we report that a developmental timing regulator, BLMP-1/BLIMP1, governs the temporal response to dietary restriction (DR). At the end of larval development, BLMP-1 is induced and interacts with DR-activated PHA-4/FOXA, a key...

Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)-a transcription factor known to regulate expression of actin and actin regulators in other cell types-as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the mechanistic role of SRF in...

The etiology of hair loss remains enigmatic, and current remedies remain inadequate. Transcriptome analysis of aging hair follicles uncovered changes in immune pathways, including Toll-like receptors (TLRs). Our findings demonstrate that the maintenance of hair follicle homeostasis and the regeneration capacity after damage depend on TLR2 in hair follicle stem cells (HFSCs). In healthy hair follicles, TLR2 is expressed in a cycle-dependent manner and governs HFSCs activation by countering...

Ion trapping has been found to be responsible for the performance degradation in electrochromic oxide thin films, and a detrapping procedure was proved to be effective to rejuvenate the degraded films. Despite of the studies on ion trapping and detrapping, its dynamics remain largely unknown. Moreover, coloration mechanisms of electrochromic oxides are also far from clear, limiting the development of superior devices. Here, we visualize ion trapping and detrapping dynamics in a model...

Understanding how and why menopause has evolved is a long-standing challenge across disciplines. Females can typically maximize their reproductive success by reproducing for the whole of their adult life. In humans, however, women cease reproduction several decades before the end of their natural lifespan^(1,2). Although progress has been made in understanding the adaptive value of menopause in humans^(3,4), the generality of these findings remains unclear. Toothed whales are the only mammal...

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Tryptophan catabolism is highly conserved and generates important bioactive metabolites, including kynurenines, and in some animals, NAD^(+) . Aging and inflammation are associated with increased levels of kynurenine pathway (KP) metabolites and depleted NAD^(+) , factors which are implicated as contributors to frailty and morbidity. Contrastingly, KP suppression and NAD^(+) supplementation are associated with increased life span in some animals. Here, we used DGRP_229 Drosophila to elucidate...

Weakened germinal center responses by the aged immune system result in diminished immunity against pathogens and reduced efficacy of vaccines. Prolonged contacts between activated B cells and CD4^(+) T cells are crucial to germinal center formation and T follicular helper cell (Tfh) differentiation, but it is unclear how aging impacts the quality of this interaction. Peptide immunization confirmed that aged mice have decreased expansion of antigen-specific germinal center B cells and reduced...