Aging & Longevity

Exercise has well-established health benefits, yet its molecular underpinnings remain incompletely understood. We conducted an integrated multi-omics analysis to compare the effects of acute vs. long-term exercise in healthy males. Acute exercise induced transient responses, whereas repeated exercise triggered adaptive changes, notably reducing cellular senescence and inflammation and enhancing betaine metabolism. Exercise-driven betaine enrichment, partly mediated by renal biosynthesis, exerts...

Chronic obstructive pulmonary disease (COPD) is the world's fourth highest reason for mortality, accounting for 3.5 million deaths in 2021, and about 5 % of total global deaths. Emphysema and chronic bronchitis are the two major pathologies of COPD. Tobacco smoke, dust, vapors, and fumes, outdoor air pollutants, genetic factors, ageing, infections, and asthma are the risk factors of COPD. On the other hand, senescence is permanent halt in cell cycle accompanied by phenotypic alterations due to...

Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal that silencing specific vacuolar H^(+)-ATPase subunits (for example, vha-6), which are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%. This longevity phenotype can be explained by an adaptive...

Small non-coding RNAs coordinate essential cellular processes, including gene expression regulation, genome stability maintenance, and transposon suppression. These processes determine aging, lifespan, and resistance of cells and organisms to stress. In this work, we conducted a comprehensive study of the geroprotective effects of overexpression of two Dicer family genes (Dcr-1 and Dcr-2, which are responsible for the biogenesis of miRNAs and siRNAs) in different tissues of Drosophila...

Immune cells navigate through complex tissue architectures by extensive cellular deformation, low adhesion, and high cell velocities. Loss-of-function mutations in Dedicator of Cytokinesis 8 (Dock8) are associated with immunodeficiency as immune cells becoming entangled during migration through dense environments, but their migration on two-dimensional surfaces remains entirely intact. Here we investigated the specific cytoskeletal defect of Dock8-deficient activated T cells and describe a...

α-ketoglutaric acid (AKG), a tricarboxylic acid cycle metabolite central to aerobic metabolism and longevity, retains unresolved anti-aging protein targets. Here, we demonstrate that reduced isocitrate dehydrogenase 1 (IDH1) expression during senescence lowers AKG production, accelerating the aging of mesenchymal stem cells (MSCs). Exogenous AKG or IDH1 overexpression restores AKG levels, enabling 2-oxoglutarate and Fe(II)-dependent oxygenase domain-containing protein 1 (OGFOD1)-catalyzed...

Lipophagy engulfs lipid droplets and delivers them to lysosomes for degradation. We found that lipophagy levels were low in most fly tissues, except for the prothoracic gland (PG) during larval development. Therefore, we performed a small-scale screening in the PG to identify regulators of lipophagy. We discovered that the loss of nmd, a gene encoding a mitochondrial AAA-ATPase, led to developmental failure and reduced lipophagy in the PG. Further studies indicated that nmd was not only required...

Liquid-liquid phase separation (LLPS) has emerged as a major organizing principle in cells. Recent work showed that multiple components of integrin-mediated focal adhesions, including p130Cas can form LLPS, which govern adhesion dynamics and related cell behaviors. In this study, we found that the focal adhesion protein p130Cas drives the formation of structures with the characteristics of LLPS that bud from focal adhesions into the cytoplasm. Condensing concentrated cytoplasm around...

Lens epithelial cell (LEC) senescence is one of the key pathological processes of age-related cataract (ARC) and is associated with oxidative stress, mitochondrial dysfunction, and protein aggregation. This study aimed to elucidate the pathogenesis of LEC senescence in ARC. The protein expression level of silencing regulatory protein 1 (SIRT1) and aptamer protein (p66Shc) was quantified. Reactive oxygen species (ROS) and mitochondrial superoxide levels were measured to evaluate cellular...

As organisms age, somatic stem cells progressively lose their ability to sustain tissue homeostasis and support regeneration. Although stem cells are relatively shielded from some cellular aging mechanisms compared with their differentiated progeny, they remain vulnerable to both intrinsic and extrinsic stressors. In this review, we delineate five cardinal features that characterize aged stem cells and examine how these alterations underlie functional decline across well-studied stem cell...

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Aging and age-related disorders are significant global health concerns, driving interest in potential preventative strategies. In this study, we established a high-throughput screening system to reveal the effects of quinacrine and rimonabant on lifespan extension in C. elegans. Mechanistically, quinacrine influences the metabolic and immune pathways through the insulin/insulin-like growth factor (IIS) pathway, as it fails to prolong longevity in IIS pathway mutants while boosting the expression...

CONCLUSION: As SSN is closely tied to biomechanical function, these findings present SSN as a distinct target for improving muscle performance in older adults.

CONCLUSION: Precision care interventions of biomarkers monitoring implemented into chronic disease follow-up on the CRP or Hs-CRP as well as IL-6 levels may reduce the risk of mortality and depression.

Dysregulation of redox homeostasis is implicated in the ageing process and the pathology of age-related diseases. To study redox signalling by H(2)O(2) in vivo, we established a redox-shifted model by manipulating levels of the H(2)O(2)-degrading enzyme catalase in Drosophila. Here we report that ubiquitous over-expression of catalase robustly extends lifespan in females. As anticipated, these flies are strongly resistant to a range of oxidative stress challenges, but interestingly are sensitive...

Osteoimmunology is an interdisciplinary branch of immunology which studies the interplay of skeletal and immune systems. Both spatial and functional connections exist between the two systems, as most immune cells are generated in the bone marrow microenvironment, which facilitates the communication between the two systems. Moreover, immune cytokines such as RANKL (receptor activating Nf-kB ligand) and non-immune soluble mediators such as osteoprotegrin (OPG), made by immune and bone cells,...

In vivo reprogramming through the forced expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) has demonstrated great potential for reversing age-associated phenotypes. However, continuous in vivo OSKM expression has raised safety concerns due to loss of cell identity, decrease in body weight, and premature death. Although cyclic short-term or targeted expression of the reprogramming factors can mitigate some of these detrimental effects, systemic rejuvenation of wild-type mice has remained elusive....

In the general population, aging is associated with an increase in systemic inflammation and chronic disease burden. However, in systemic lupus erythematosus (SLE), older age is uniquely associated with a decrease in disease activity, suggesting a distinct relationship between aging and inflammation. Using a multiomic approach, we compared aging-related changes in the peripheral blood immune profiles of 287 patients with SLE and 928 healthy controls. In patients with SLE, aging correlated with...

ObjectivesThis study examines whether social strain and support from various sources are associated with accumulation of chronic conditions in older adults.MethodsGrowth mixture modeling was used to investigate which network sources of support and strain were related to morbidity accumulation over 12 years among 5,321 individuals over age 50 in the Health and Retirement Study.ResultsHigher overall social support-comfort provided by others-was associated with a greater likelihood of belonging to...

Exacerbating the DNA replication problems of cancer cells serves as a viable therapeutic approach. Nevertheless, the cytotoxicity of cancer drugs is often hampered by therapy-induced senescence, leading to unfavorable patient outcomes. Here, we employ acute replisome dysfunction in combination with Ataxia telangiectasia and Rad3-related (ATR) inhibition as a strategy to divert senescent cells toward death by triggering DNA replication catastrophe, a form of irreversible replication fork collapse...