Aging & Longevity
Somatic mutations in human ageing: New insights from DNA sequencing and inherited mutations
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...
Unveiling the interplay of AMPK/SIRT1/PGC-1alpha axis in brain health: Promising targets against aging and NDDs
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...
Photo-neuro-immuno-endocrinology: How the ultraviolet radiation regulates the body, brain, and immune system
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...
The chromatin factors SET-26 and HCF-1 oppose the histone deacetylase HDA-1 in longevity and gene regulation in C. elegans
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...
Global Healthspan Summit 2023: closing the gap between healthspan and lifespan
No abstract
The sirtuin-associated human senescence program converges on the activation of placenta-specific gene PAPPA
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...
A serine metabolic enzyme is flexing its muscle to help repair skeletal muscle
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...
BLMP-1 is a critical temporal regulator of dietary-restriction-induced response in Caenorhabditis elegans
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...
SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination
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...
TLR2 regulates hair follicle cycle and regeneration via BMP signaling
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...
Capturing ion trapping and detrapping dynamics in electrochromic thin films
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...
The evolution of menopause in toothed whales
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...
Antibodies drive adipose tissue ageing
No abstract
Dual treatment with kynurenine pathway inhibitors and NAD<sup>+</sup> precursors synergistically extends life span in Drosophila
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...
The aged microenvironment impairs BCL6 and CD40L induction in CD4<sup>+</sup> T follicular helper cell differentiation
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...
Mitophagy defect mediates the aging-associated hallmarks in Hutchinson-Gilford progeria syndrome
Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal disease manifested by premature aging and aging-related phenotypes, making it a disease model for aging. The cellular machinery mediating age-associated phenotypes in HGPS remains largely unknown, resulting in limited therapeutic targets for HGPS. In this study, we showed that mitophagy defects impaired mitochondrial function and contributed to cellular markers associated with aging in mesenchymal stem cells derived from HGPS...
IL-4-ever young: Type 2 cytokine signaling in macrophages slows aging
Macrophages activated via the IL-4 receptor possess non-immune functions that support tissue homeostasis, but their specific role in aging is unknown. In this issue of Immunity, Zhou et al. show that IL-4 extends lifespan by inducing DNA repair pathways that protect macrophages from cellular senescence.
Predicting plasma cell retention and loss over a lifetime
Plasma cells (PCs) rely on external survival cues for persistence, which limits the size of the PC pool. How, then, are new specificities incorporated into a saturated system? In this issue of Immunity, Simons and Karin put forward a mathematical framework to explain PC retention that makes testable predictions about steady-state lifespan structure, withstands tests based on accrual and displaceability, and accounts for lifespan stratification with specificity.
Neuronal ageing is promoted by the decay of the microtubule cytoskeleton
Natural ageing is accompanied by a decline in motor, sensory, and cognitive functions, all impacting quality of life. Ageing is also the predominant risk factor for many neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. We need to therefore gain a better understanding of the cellular and physiological processes underlying age-related neuronal decay. However, gaining this understanding is a slow process due to the large amount of time required to age mammalian or...
The Effects of the Flint water crisis on the educational outcomes of school-age children
In 2014, the municipal water source in Flint, Michigan was switched, causing lead from aging pipes to leach into the city's drinking water. While lead exposure in Flint children increased modestly on average, some children were exposed to high lead levels. Surveys of Flint residents show the water crisis was also associated with increased levels of stress, anxiety, and depression. We use Michigan's administrative education data and utilize synthetic control methods to examine the impact of the...
Aging and Longevity: Latest results from PubMed
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