Ginsenoside Rg1, the main active component of Panax ginseng, has been shown to improve mitochondrial function and delay cell aging by regulating chaperone-mediated mitophagy. However, how Rg1 works in Caenorhabditis elegans is still unclear. In this study, C. elegans was used as a model to study how Rg1 regulates autophagy and mitochondrial function, and to understand its anti-aging mechanism. The results showed that Rg1 treatment significantly kept cells alive and maintained muscle shape in aged C. elegans, and effectively extended their lifespan. Further studies found that Rg1 improved mitochondrial function by activating mitophagy, which helped the C. elegans better resist oxidative stress. In addition, by combining RNA sequencing and bioinformatics analysis, the transcription factor daf-16 was identified as a key target of Rg1. Experiments using daf-16 knockout strains confirmed that Rg1 produced its anti-aging effects through the daf-16 pathway, in which the activation of mitophagy and the improvement of antioxidant ability were both mediated by daf-16. In conclusion, this study shows that Rg1 slows aging in C. elegans through a daf-16-mediated mitophagy pathway, providing experimental support for the study and use of natural products in anti-aging research.
Minimal hepatic encephalopathy (MHE) is a neurological complication associated with chronic liver disease characterized by subtle cognitive impairment and neuroinflammation, particularly in the aging population. However, the molecular mechanisms underlying age-associated MHE remain poorly understood. The present study investigated the role of Fetuin-A-mediated neuroinflammation and its potential as a therapeutic target in the management of MHE in old rats using pioglitazone in a thioacetamide (TAA)-induced MHE model in aged rats. Old male rats were administered TAA (50 mg/kg) for 14 days to induce MHE, followed by pioglitazone treatment (3 mg/kg) for 7 days. Western blot and immunofluorescence analyses revealed elevated hippocampal Fetuin-A expression in MHE rats, accompanied by activation of the TLR4/MyD88/NF-κB signaling pathway and increased inflammatory cytokines (IL-6 and TNF-α). Pioglitazone treatment significantly reduced Fetuin-A expression and was accompanied by reduced TLR4, MyD88 and nuclear NF-κB expression, and by decreased astrocyte activation Furthermore, histological and Golgi-Cox analyses demonstrated restoration of neuronal density, dendritic arborization, and spine density in the hippocampus of pioglitazone-treated old MHE rats. Behavioral analyses further confirmed the molecular and histological findings. Thus, elevated hippocampal Fetuin-A is associated with TLR4/MyD88/NF-κB activation in aged MHE rats, and its pharmacological reduction by pioglitazone is accompanied by reduced neuroinflammation, restored hippocampal cytoarchitecture and recovered recognition memory. A causal role for Fetuin-A remains to be established by direct perturbation.
Cellular senescence is characterized by coordinated disruptions in mitochondrial function and epigenetic regulation, with perturbation of the mitochondria–chromatin axis emerging as a central hallmark of this process. Resveratrol (RSV) has been extensively investigated as a modulator of this axis; however, its clinical utility is constrained by dose-dependent cytotoxicity. Here, we evaluated the safety profile and anti-aging potential of resveratrol glucoside (R-glc), a glucosylated derivative of RSV. R-glc exhibited markedly reduced cytotoxicity compared to RSV and effectively attenuated multiple senescence-associated phenotypes at low concentrations. Mechanistically, R-glc enhanced mitochondrial function, as evidenced by increased oxidative phosphorylation and reduced glycolytic dependence. At the epigenetic level, R-glc upregulated the NAD+-dependent deacetylase SIRT6 and decreased histone H3 lysine 9 (H3K9) acetylation, indicating improved chromatin stability. Taken together, these findings identify R-glc as a safer and functionally effective modulator of the mitochondria–chromatin axis, supporting its potential as a clinically applicable intervention for age-related functional decline.
Aging is modulated by conserved nutrient-sensing pathways that integrate metabolic cues to regulate growth, stress resilience, and lifespan. Caloric restriction (CR) extends longevity across species, motivating the search for compounds that engage related physiology. Lysergic acid diethylamide (LSD), a classic serotonergic psychedelic with emerging therapeutic applications, remains unexplored in the context of aging. Here we show that chronic exposure to nanomolar LSD extends lifespan in Caenorhabditis elegans by up to 17.6
What explains the large variation in lifespan across species? I examine an information-turnover proposition—that ancestral environmental variability should shorten captive lifespan after controlling for body mass, temperature and extrinsic mortality (P1), with a possible lineage-fate interaction (P2)—against the classical extrinsic-mortality prediction that safer niches permit longer life. I state the decision rules in advance rather than register a third-party protocol. Integrating AnAge (4,219 records), PanTHERIA, WorldClim/CHELSA climate and a 4,100-species mammal phylogeny with Pagel’s-λ phylogenetic generalized least squares (PGLS), together with Paleobiology Database fossils across two mass extinctions, the lifespan–mass scaling reproduces (slopes 0.158 mammals, 0.212 birds; P < 10⁻140). P1 is not supported under the most conservative specifications: weak proxy signals attenuate or reverse at λ = 1 and under family fixed effects, and the set of analyses is best read as overlapping sensitivity and robustness checks rather than independent falsifications; equivalence intervals for the climate coefficients exclude large (arboreality-sized) effects but not small ones. A basal-metabolic-rate correlate likewise dissolves at λ = 1. Turning the same pipeline to niche safety, flight, arboreality, aquatic life and hibernation carry positive mass-corrected coefficients in raw and maximum-likelihood-λ contrasts; at λ = 1 in a joint model (n = 652) only multiply-origin arboreality is significant (b = + 0.106 dex, 95
