Aging & Longevity

Lipoteichoic acid restrains macrophage senescence via β-catenin/FOXO1/REDD1 pathway in age-related osteoporosis

3 months 1 week ago
Osteoporosis and its related fractures are common causes of morbidity and mortality in older adults, but its underlying molecular and cellular mechanisms remain largely unknown. In this study, we found that lipoteichoic acid (LTA) treatment could ameliorate age-related bone degeneration and attenuate intramedullary macrophage senescence. FOXO1 signaling, which was downregulated and deactivated in aging macrophages, played a key role in the process. Blocking FOXO1 signaling caused decreased REDD1...
Weike Cheng

VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes

3 months 1 week ago
The mechanistic target of rapamycin complex 1 (mTORC1) is a crucial regulator of cell growth. It senses nutrient signals and adjusts cellular metabolism accordingly. Deregulation of mTORC1 has been associated with metabolic diseases, cancer, and aging. Amino acid signals are transduced to mTORC1 through sensor proteins and two protein complexes named GATOR1 and GATOR2. In this study, we identify VWCE (von Willebrand factor C and EGF domains) as a negative regulator of amino acid-dependent mTORC1...
Tianyu Zhao

Adult stem cell activity in naked mole rats for long-term tissue maintenance

3 months 1 week ago
The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5^(+)) in their native in vivo state, we find an expanded pool of Lgr5^(+) cells in NMRs, and these cells specifically at the crypt base (Lgr5^(+CBC)) exhibit slower division rates...
Shamir Montazid

Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response

3 months 1 week ago
Gain-of-function mutations in stimulator of interferon gene 1 (STING1) result in STING-associated vasculopathy with onset in infancy (SAVI), a severe autoinflammatory disease. Although elevated type I interferon (IFN) production is thought to be the leading cause of the symptoms observed in patients, STING can induce a set of pathways, which have roles in the onset and severity of SAVI and remain to be elucidated. To this end, we performed a multi-omics comparative analysis of peripheral blood...
Camille de Cevins

Senescent skeletal muscle fibroadipogenic progenitors recruit and promote M2 polarization of macrophages

3 months 1 week ago
Senescent cells compromise tissue structure and function in older organisms. We recently identified senescent fibroadipogenic progenitors (FAPs) with activated chemokine signaling pathways in the skeletal muscle of old mice, and hypothesized these cells may contribute to the age-associated accumulation of immune cells in skeletal muscle. In this study, through cell-cell communication analysis of skeletal muscle single-cell RNA-sequencing data, we identified unique interactions between senescent...
Xu Zhang

Gss deficiency causes age-related fertility impairment via ROS-triggered ferroptosis in the testes of mice

3 months 1 week ago
Glutathione synthetase (GSS) catalyzes the final step in the synthesis of glutathione (GSH), a well-established antioxidant. Research on the specific roles of the Gss gene during spermatogenesis remains limited due to the intricate structure of testis. In this study, we identified pachytene spermatocytes as the primary site of GSS expression and generated a mouse model with postnatal deletion of Gss using Stra8-Cre (S8) to investigate the role of GSS in germ cells. The impact of Gss knockout on...
Haixia Zhu

Mendelian randomization study supports the causal effects of air pollution on longevity via multiple age-related diseases

3 months 1 week ago
Growing evidence suggests that exposure to fine particulate matter (PM(2.5)) may reduce life expectancy; however, the causal pathways of PM(2.5) exposure affecting life expectancy remain unknown. Here, we assess the causal effects of genetically predicted PM(2.5) concentration on common chronic diseases and longevity using a Mendelian randomization (MR) statistical framework based on large-scale genome-wide association studies (GWAS) (>400,000 participants). After adjusting for other types of...
Shizheng Qiu

A pair of RNA binding proteins inhibit ion transporter expression to maintain lifespan

3 months 1 week ago
Regulation of lifespan by transcription factors has been well established. More recently a role for RNA binding proteins (RBPs) in regulating lifespan has also emerged. In both cases, a major challenge is to determine which regulatory targets are functionally responsible for the observed lifespan phenotype. We recently identified a pair of neuronal RBPs, exc-7/ELAVL and mbl-1/Muscleblind, which in C. elegans display synthetic (non-additive) lifespan defects: single mutants do not affect...
Rebekah Napier-Jameson

Projections of human kinship for all countries

3 months 1 week ago
Demographers have long attempted to project future changes in the size and composition of populations, but have ignored what these processes will mean for the size, composition, and age distribution of family networks. Kinship structures matter because family solidarity-a crucial source of informal care for millions of people around the world-is conditional on kin being alive. Here, we present innovative projections of biological kin for the 1950 to 2100 period and discuss what they imply for...
Diego Alburez-Gutierrez

A dicer-related helicase opposes the age-related pathology from SKN-1 activation in ASI neurons

3 months 1 week ago
Coordination of cellular responses to stress is essential for health across the lifespan. The transcription factor SKN-1 is an essential homeostat that mediates survival in stress-inducing environments and cellular dysfunction, but constitutive activation of SKN-1 drives premature aging thus revealing the importance of turning off cytoprotective pathways. Here, we identify how SKN-1 activation in two ciliated ASI neurons in Caenorhabditis elegans results in an increase in organismal...
Chris D Turner

Divergent bleaching and recovery trajectories in reef-building corals following a decade of successive marine heatwaves

3 months 1 week ago
Increasingly frequent marine heatwaves are devastating coral reefs. Corals that survive these extreme events must rapidly recover if they are to withstand subsequent events, and long-term survival in the face of rising ocean temperatures may hinge on recovery capacity and acclimatory gains in heat tolerance over an individual's lifespan. To better understand coral recovery trajectories in the face of successive marine heatwaves, we monitored the responses of bleaching-susceptible and...
Kristen T Brown

Aged intestinal stem cells propagate cell-intrinsic sources of inflammaging in mice

3 months 1 week ago
Low-grade chronic inflammation is a hallmark of ageing, associated with impaired tissue function and disease development. However, how cell-intrinsic and -extrinsic factors collectively establish this phenotype, termed inflammaging, remains poorly understood. We addressed this question in the mouse intestinal epithelium, using mouse organoid cultures to dissect stem cell-intrinsic and -extrinsic sources of inflammaging. At the single-cell level, we found that inflammaging is established...
Maja C Funk

Network-based cytokine inference implicates Oncostatin M as a driver of an inflammation phenotype in knee osteoarthritis

3 months 1 week ago
Inflammatory cytokines released by synovium after trauma disturb the gene regulatory network and have been implicated in the pathophysiology of osteoarthritis. A mechanistic understanding of how aging perturbs this process can help identify novel interventions. Here, we introduced network paradigms to simulate cytokine-mediated pathological communication between the synovium and cartilage. Cartilage-specific network analysis of injured young and aged murine knees revealed aberrant matrix...
Hirotaka Iijima

Trioxidized cysteine in the aging proteome mimics the structural dynamics and interactome of phosphorylated serine

3 months 1 week ago
Aging is the primary risk factor for the development of numerous human chronic diseases. On a molecular level, it significantly impacts the regulation of protein modifications, leading to the accumulation of degenerative protein modifications (DPMs) such as aberrant serine phosphorylation (p-Ser) and trioxidized cysteine (t-Cys) within the proteome. The altered p-Ser is linked to abnormal cell signaling, while the accumulation of t-Cys is associated with chronic diseases induced by oxidative...
Jose Antonio Sánchez Milán

Functional-metabolic coupling in distinct renal cell types coordinates organ-wide physiology and delays premature ageing

3 months 1 week ago
Precise coupling between cellular physiology and metabolism is emerging as a vital relationship underpinning tissue health and longevity. Nevertheless, functional-metabolic coupling within heterogenous microenvironments in vivo remains poorly understood due to tissue complexity and metabolic plasticity. Here, we establish the Drosophila renal system as a paradigm for linking mechanistic analysis of metabolism, at single-cell resolution, to organ-wide physiology. Kidneys are amongst the most...
Jack Holcombe

iMUT-seq: high-resolution DSB-induced mutation profiling reveals prevalent homologous-recombination dependent mutagenesis

3 months 1 week ago
DNA double-strand breaks (DSBs) are the most mutagenic form of DNA damage, and play a significant role in cancer biology, neurodegeneration and aging. However, studying DSB-induced mutagenesis is limited by our current approaches. Here, we describe iMUT-seq, a technique that profiles DSB-induced mutations at high-sensitivity and single-nucleotide resolution around endogenous DSBs. By depleting or inhibiting 20 DSB-repair factors we define their mutational signatures in detail, revealing insights...
Aldo S Bader

Cpne7 deficiency induces cellular senescence and premature aging of dental pulp

3 months 1 week ago
Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in...
Yoon Seon Lee

Age-associated changes in lineage composition of the enteric nervous system regulate gut health and disease

3 months 1 week ago
The enteric nervous system (ENS), a collection of neural cells contained in the wall of the gut, is of fundamental importance to gastrointestinal and systemic health. According to the prevailing paradigm, the ENS arises from progenitor cells migrating from the neural crest and remains largely unchanged thereafter. Here, we show that the lineage composition of maturing ENS changes with time, with a decline in the canonical lineage of neural-crest derived neurons and their replacement by a newly...
Subhash Kulkarni

Obesity paradox in older sarcopenic adults - a delay in aging: A systematic review and meta-analysis

3 months 1 week ago
The prognostic significance of obesity in sarcopenic adults is controversial. This systematic review and meta-analysis aimed to investigate the effect of additional obesity on health outcomes in sarcopenia. MEDLINE, EMBASE, Scopus and CENTRAL were systematically searched for studies to compare health outcomes of adults with sarcopenic obesity (SO) to those of sarcopenic non-obese (SNO) adults. We also considered the methods of assessing obesity. Of 15060 records screened, 65 papers were included...
Szimonetta Eitmann
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