Aging & Longevity

IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis

3 months 2 weeks ago
Cytosolic double-stranded DNA surveillance by cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) signaling triggers cellular senescence, autophagy, biased mRNA translation, and interferon-mediated immune responses. However, detailed mechanisms and physiological relevance of STING-induced senescence are not fully understood. Here, we unexpectedly found that interferon regulatory factor 3 (IRF3), activated during innate DNA sensing, forms substantial endogenous complexes in the...
Qirou Wu

Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness

3 months 2 weeks ago
Epigenetic clocks can measure aging and predict the incidence of diseases and mortality. Higher levels of physical fitness are associated with a slower aging process and a healthier lifespan. Microbiome alterations occur in various diseases and during the aging process, yet their relation to epigenetic clocks is not explored. To fill this gap, we collected metagenomic (from stool), epigenetic (from blood), and exercise-related data from physically active individuals and, by applying epigenetic...
Ferenc Torma

Epigenome-wide analysis of frailty: Results from two European twin cohorts

3 months 2 weeks ago
Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index...
Jonathan K L Mak

Binding to nucleosome poises human SIRT6 for histone H3 deacetylation

3 months 2 weeks ago
Sirtuin 6 (SIRT6) is an NAD^(+)-dependent histone H3 deacetylase that is prominently found associated with chromatin, attenuates transcriptionally active promoters and regulates DNA repair, metabolic homeostasis and lifespan. Unlike other sirtuins, it has low affinity to free histone tails but demonstrates strong binding to nucleosomes. It is poorly understood how SIRT6 docking on nucleosomes stimulates its histone deacetylation activity. Here, we present the structure of human SIRT6 bound to a...
Ekaterina Smirnova

Enhanced TRPC3 transcription through AT1R/PKA/CREB signaling contributes to mitochondrial dysfunction in renal tubular epithelial cells in D-galactose-induced accelerated aging mice

3 months 2 weeks ago
Aging-associated renal dysfunction promotes the pathogenesis of chronic kidney disease. Mitochondrial dysfunction in renal tubular epithelial cells is a hallmark of senescence and leads to accelerated progression of renal disorders. Dysregulated calcium profiles in mitochondria contribute to aging-associated disorders, but the detailed mechanism of this process is not clear. In this study, modulation of the sirtuin 1/angiotensin II type 1 receptor (Sirt1/AT1R) pathway partially attenuated renal...
Bin Wang

Accelerated elastin degradation by age-disease interaction: a common feature in age-related diseases

3 months 2 weeks ago
Aging is a major driving force for many diseases but the relationship between chronological age, the aging process and age-related diseases is not fully understood. Fragmentation and loss of ultra-long-lived elastin are key features in aging and several age-related diseases leading to increased mortality. By comparing the relationship between age and elastin turnover with healthy volunteers, we show that accelerated elastin turnover by age-disease interaction is a common feature of age-related...
Naomi Shek

Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models

3 months 2 weeks ago
Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-month-old golden Syrian hamsters (GSH) and 22-23-month-old K18-hCAE2 mice were immunised twice with S-29 protein in AddaVax^(TM) adjuvant. GSH were intranasally inoculated with SARS-CoV-2 either two...
Carla Usai

Impact of population aging on future temperature-related mortality at different global warming levels

3 months 2 weeks ago
Older adults are generally amongst the most vulnerable to heat and cold. While temperature-related health impacts are projected to increase with global warming, the influence of population aging on these trends remains unclear. Here we show that at 1.5 °C, 2 °C, and 3 °C of global warming, heat-related mortality in 800 locations across 50 countries/areas will increase by 0.5%, 1.0%, and 2.5%, respectively; among which 1 in 5 to 1 in 4 heat-related deaths can be attributed to population aging....
Kai Chen

Your move: A precision medicine framework for physical activity in aging

3 months 2 weeks ago
The accelerating digital health landscape, coupled with the proliferation of wearable devices and advanced neuroimaging, offers an unprecedented avenue to develop precision interventions for enhancing physical activity in aging. This approach requires deep baseline phenotyping to match older adults with the intervention poised to yield maximal health benefits. However, building sufficient evidence to translate precision physical activity recommendations into clinical practice requires a...
Adrián Noriega de la Colina

Inhibition of S6K lowers age-related inflammation and increases lifespan through the endolysosomal system

3 months 2 weeks ago
Suppression of target of rapamycin complex 1 (TORC1) by rapamycin ameliorates aging in diverse species. S6 kinase (S6K) is an essential mediator, but the mechanisms involved are unclear. Here we show that activation of S6K specifically in Drosophila fat-body blocked extension of lifespan by rapamycin, induced accumulation of multilamellar lysosomes and blocked age-associated hyperactivation of the NF-κB-like immune deficiency (IMD) pathway, indicative of reduced inflammaging. Syntaxin 13...
Pingze Zhang

Low-frequency somatic mutations are heritable in tropical trees <em>Dicorynia guianensis</em> and <em>Sextonia rubra</em>

3 months 2 weeks ago
Somatic mutations potentially play a role in plant evolution, but common expectations pertaining to plant somatic mutations remain insufficiently tested. Unlike in most animals, the plant germline is assumed to be set aside late in development, leading to the expectation that plants accumulate somatic mutations along growth. Therefore, several predictions were made on the fate of somatic mutations: mutations have generally low frequency in plant tissues; mutations at high frequency have a higher...
Sylvain Schmitt

A unified framework for evolutionary genetic and physiological theories of aging

3 months 2 weeks ago
Why and how we age are 2 intertwined questions that have fascinated scientists for many decades. However, attempts to answer these questions remain compartmentalized, preventing a comprehensive understanding of the aging process. We argue that the current lack of knowledge about the evolution of aging mechanisms is due to a lack of clarity regarding evolutionary theories of aging that explicitly involve physiological processes: the disposable soma theory (DST) and the developmental theory of...
Jean-François Lemaître

Neuronal waste management: new roles for autophagy genes in the extrusion of protein aggregates and in longevity

3 months 2 weeks ago
A decline in macroautophagic/autophagic activity with age contributes to the accumulation of damaged molecules and is associated with the impairment of neuronal functions and the onset of age-related diseases, particularly neurodegenerative disorders. To learn about the neuronal-specific roles of autophagy genes in aging, we specifically inhibited autophagy genes pan-neuronally in C. elegans, which leads to unexpected positive impacts on neuronal homeostasis including polyQ aggregate load and...
Ling-Hsuan Sun

Aging STINGs: mitophagy at the crossroads of neuroinflammation

3 months 2 weeks ago
Loss of proteostasis and dysregulated mitochondrial function are part of the traditional hallmarks of aging, and in their last revision impaired macroautophagy and chronic inflammation are also included. Mitophagy is at the intersection of all these processes but whether it undergoes age-associated perturbations was not known. In our recent work, we performed a systematic and systemic analysis of mitolysosome levels in mice and found that, despite the already-known decrease in nonselective...
Juan Ignacio Jiménez-Loygorri

Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer's disease progression

3 months 2 weeks ago
Ageing increases susceptibility to neurodegenerative disorders, such as Alzheimer's disease (AD). Serum levels of sclerostin, an osteocyte-derived Wnt-β-catenin signalling antagonist, increase with age and inhibit osteoblastogenesis. As Wnt-β-catenin signalling acts as a protective mechanism for memory, we hypothesize that osteocyte-derived sclerostin can impact cognitive function under pathological conditions. Here we show that osteocyte-derived sclerostin can cross the blood-brain barrier of...
Tianshu Shi

Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice

3 months 2 weeks ago
Foxo family transcription factors are critically involved in multiple processes, such as metabolism, quiescence, cell survival and cell differentiation. Although continuous, high activity of Foxo transcription factors extends the life span of some species, the involvement of Foxo proteins in mammalian aging remains to be determined. Here, we show that Foxo1 is down-regulated with age in mouse T cells. This down-regulation of Foxo1 in T cells may contribute to the disruption of naive T-cell...
Aurélie Durand

A homoeostatic switch causing glycerol-3-phosphate and phosphoethanolamine accumulation triggers senescence by rewiring lipid metabolism

3 months 2 weeks ago
Cellular senescence affects many physiological and pathological processes and is characterized by durable cell cycle arrest, an inflammatory secretory phenotype and metabolic reprogramming. Here, by using dynamic transcriptome and metabolome profiling in human fibroblasts with different subtypes of senescence, we show that a homoeostatic switch that results in glycerol-3-phosphate (G3P) and phosphoethanolamine (pEtN) accumulation links lipid metabolism to the senescence gene expression...
Khaled Tighanimine

Histone deficiency and hypoacetylation in the aging retinal pigment epithelium

3 months 2 weeks ago
Histones serve as a major carrier of epigenetic information in the form of post-translational modifications which are vital for controlling gene expression, maintaining cell identity, and ensuring proper cellular function. Loss of histones in the aging genome can drastically impact the epigenetic landscape of the cell leading to altered chromatin structure and changes in gene expression profiles. In this study, we investigated the impact of age-related changes on histone levels and histone...
Sushil K Dubey
4 hours 27 minutes ago
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