BiogerontologyPub Date : 2025-06-25DOI: 10.1007/s10522-025-10274-3
Omidreza Salehi, Dariush Sheikholeslami-Vatani, Seyed Ali Hosseini
{"title":"Positive effects of HIIT and vitamin E on cognitive function, angiogenesis and NRF2 antioxidant pathway in male rats with Alzheimer's disease.","authors":"Omidreza Salehi, Dariush Sheikholeslami-Vatani, Seyed Ali Hosseini","doi":"10.1007/s10522-025-10274-3","DOIUrl":"https://doi.org/10.1007/s10522-025-10274-3","url":null,"abstract":"<p><p>Interactive effects of exercise and antioxidant supplements are still not well known. So, The aim of this study was to investigate the effects of high intensity interval training (HIIT) and vitamin E (VE) on the PI3K/NRF2 pathway in the hippocampus of Alzheimer's disease rats (AD). In this expremantal study, fifty aged AD rats with 10 mg/kg trimethyltin (TMT), were divided into groups 1) TMT, 2) VE solvent (Sham), 3) VE (30 mg/kg), 4) HIIT (90-95% of the maximum running speed) and 5) HIIT+VE. Ten healthy rats were included in the healthy control group to investigate the effect of TMT on research variables. Results Showed that, HIIT, VE and HIIT+VE decreased amyloid beta (P≤0.05), HIIT and HIIT+VE decreased NF-kB (P≤0.05) as well as HIIT, VE and HIIT+VE increased SOD and decreased MDA. HIIT simultaneously with VE increased PI3K, NRF2, and Cat. HIIT, VE and the interaction of HIIT and VE decreased the expression of miR-125b and increased expression of miR-132 (P≤0.05); The combination of HIIT and VE increased capillary density in areas 1 and 3, the percentage of healthy cells in C1 and C3 areas of the hippocampus (P≤0.05). The effects of HIIT and HIIT+VE on improving memory were better than VE (P≤0.05). It seems that HIIT and VE can synergistically increase the expression of antioxidant genes from the PI3K/NRF2 pathway by decreasing miR-125 and increasing miR-132. Probably, this happens by reducing some AD markers, increasing angiogenesis and cell protection as well as cognitive memory in AD situation.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"129"},"PeriodicalIF":4.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms of endothelial senescence and vascular aging.","authors":"Qiao Li, Zonghao Qian, Yuzhen Huang, Xiao Yang, Jiankun Yang, Nanyin Xiao, Guangyu Liang, Heng Zhang, Yanguang Fu, Yan Lin, Cuntai Zhang, Anding Liu","doi":"10.1007/s10522-025-10279-y","DOIUrl":"https://doi.org/10.1007/s10522-025-10279-y","url":null,"abstract":"<p><strong>Scope: </strong>Cardiovascular disease (CVD) is a major cause of mortality, especially in the aging population. Aging is one of the main risk factors contributing to CVD, leading to early mortality and a decline in the quality of life. Vascular aging is closely linked with atherosclerosis, diabetes, hypertension, stroke, heart failure, and peripheral arterial diseases. Elucidating the cellular and molecular mechanisms underlying vascular aging help to develop therapeutic strategies that can address age-related vascular diseases and decrease the rate of morbidity and mortality among the older population. Endothelial cells located on the interior layer of blood vessels. Intima layers of vascular vessels are damaged and remodeled during vascular aging. The dysfunction of smooth muscle cells and endothelial cells plays key roles in vascular aging. Common pathological changes during vascular aging include arterial stiffness, calcification, and atherosclerosis. Endothelial cell senescence is driven by complex underlying mechanisms. The complex regulation of aging and antiaging network in endothelial cells involve several factors, such as Klotho protein, nitric oxide, fibroblast growth factor 21 (FGF21), and SIRT family members.</p><p><strong>Objectives: </strong>This review aims to systematically delineate the mechanisms underlying the endothelial senescence.</p><p><strong>Methodology: </strong>The publications on the endothelial cell senescence mechanisms and its roles in vascular aging and aging related diseases are comprehensively investigated and summarized. In this review, the roles of various components in endothelial cell senescence are discussed to elucidate the underlying molecular mechanisms of endothelial cell senescence and identify potential therapeutic targets.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"128"},"PeriodicalIF":4.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Elucidating the anti-aging bioactive compounds and mechanisms of Jingfang Granules formula based on network pharmacology and Caenorhabditis elegans.","authors":"Rui Zhao, Taili Zhao, Tingting Shi, Chuanjiao Feng, Honghua Li, Ying Xu, Qingqing Zhang, Xin Yin, Jingchun Yao, Guimin Zhang, Xuekui Xia","doi":"10.1007/s10522-025-10276-1","DOIUrl":"10.1007/s10522-025-10276-1","url":null,"abstract":"<p><p>Jingfang Granule (JFG), a traditional Chinese medicine preparation, is widely used in clinical practice. It has been shown to extend both lifespan and healthspan in the Caenorhabditis elegans model. However, the molecular mechanisms of its main constituents and their targets remain unclear. In this study, through network pharmacology, molecular docking, and experiments on C. elegans including lifespan assays and stress resistance assays, the bioactive compounds of JFG and their targets were screened. Network analysis identified a total of 187 candidate components and 150 drug-disease related targets, among which TP53, STAT3, IL6, TNF, AKT1, ESR1, CCND1, BCL2, MAPK1, and MAPK3 were the core nodes. Gene Ontology (GO) enrichment analysis revealed that these targets were mainly involved in aging-related and anti-apoptotic processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the AGE-RAGE signaling pathway, which is crucial in diabetic complications, might be involved. Experiments on Caenorhabditis elegans further confirmed that neohesperidin, kaempferol, and stigmasterol in Jingfang Granule exhibited good anti-aging effects and stress resistance. They could extend the lifespan of Caenorhabditis elegans by activating the target genes of the transcription factors DAF-16, HSF-1, and SKN-1. By combining the strategies of network pharmacology and molecular biology, this study elucidated the anti-aging mechanisms of the Jingfang Granule formula and its bioactive compounds. Therefore, the Jingfang Granule formula and its bioactive compounds hold potential for lifespan extension, healthspan improvement, and enhanced stress resistance.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"127"},"PeriodicalIF":4.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiogerontologyPub Date : 2025-06-24DOI: 10.1007/s10522-025-10269-0
Sakshi Chaudhary, Mani Raj Chaudhary, Manoj Kumar Jena, Prasana Kumar Rath, Bidyut Prava Mishra, Biswaranjan Paital, Ashish Vyas, Dipak Kumar Sahoo, Prabhakar Singh, Mohammad Murtaza Mehdi
{"title":"Calorie restriction mimetics against aging and inflammation.","authors":"Sakshi Chaudhary, Mani Raj Chaudhary, Manoj Kumar Jena, Prasana Kumar Rath, Bidyut Prava Mishra, Biswaranjan Paital, Ashish Vyas, Dipak Kumar Sahoo, Prabhakar Singh, Mohammad Murtaza Mehdi","doi":"10.1007/s10522-025-10269-0","DOIUrl":"10.1007/s10522-025-10269-0","url":null,"abstract":"<p><p>Geroprotectors, a class of compounds that ameliorate molecular, cellular, or physiological aging-related alterations, have garnered significant attention in the quest to promote healthy aging and extend the human health span. Among these, Calorie Restriction Mimetics (CRMs) have emerged as promising candidates due to their potential to mimic the benefits of calorie restriction, a dietary approach involving reduced calorie intake without malnutrition. Prospective CRMs may include biguanides (metformin and aminoguanidine), which exert effects on the insulin signaling pathway; rapamycin, which interacts with mTOR signaling pathways; and stilbenes (resveratrol), which influences stress signaling pathways and promotes the activation of AMPK, impacting mitochondrial metabolism in addition to the activity of FOXO and sirtuin. Other compounds, such as glycolytic inhibitors, carbohydrate and lipid absorption blockers, polyamines, and polyphenols, which collectively modulate pathways regulating the effects of free radicals, are also under consideration. To propose prospective geroprotective strategies, this article focuses on analyzing the functions of potential CRMs and their mechanisms demonstrating health benefits, the same as that of CR (Calorie Restriction), but without undesirable side effects.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"126"},"PeriodicalIF":4.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling mysteries of aging: the potential of melatonin in preventing neurodegenerative diseases in older adults.","authors":"Omer Unal, Nilufer Akgun-Unal, Abdulkerim Kasim Baltaci","doi":"10.1007/s10522-025-10254-7","DOIUrl":"10.1007/s10522-025-10254-7","url":null,"abstract":"<p><p>Neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, result in a substantial health problem for the elderly, marked by ongoing neuronal degeneration and a deterioration in mental faculties. These disorders are frequently linked to oxidative stress, problems with mitochondria, and persistent inflammation in the brain, which worsen neuronal damage. The neurohormone melatonin, primarily secreted by the pineal gland, has gained recognition as a promising therapeutic agent due to its antioxidant, anti-inflammatory, and neuroprotective effects. Melatonin's functions extend beyond its regulation of circadian rhythms, as research has demonstrated its ability to remove free radicals, improve mitochondrial performance, and adjust immune system responses, ultimately reducing the progression of neurodegenerative disease. Research findings from preclinical and clinical trials imply that taking melatonin supplements could lead to improved cognitive abilities, slower disease progression, and an overall better quality of life for elderly individuals suffering from neurodegenerative conditions. The mechanisms through which melatonin acts, the best dosage, and its long-term effectiveness are still being researched. This review underscores the potential benefits of melatonin as a supplementary treatment for neurodegenerative disorders in older adults, stressing the necessity for additional studies to confirm its efficacy and standardize its use in treatment plans.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"125"},"PeriodicalIF":4.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biological properties, synthetic pathways and anti-aging mechanisms of nicotinamide mononucleotide (NMN): Research progress and challenges.","authors":"Enhui Wang, Yuting Wang, Zhaofeng Zhang, Yanfei Jiang, Chunyue Zhao","doi":"10.1007/s10522-025-10270-7","DOIUrl":"https://doi.org/10.1007/s10522-025-10270-7","url":null,"abstract":"<p><p>The increasing global population aging has made the prevention and control of aging-related diseases a major public health challenge in the twenty-first century. Nicotinamide mononucleotide (NMN), as a precursor of nicotinamide adenine dinucleotide (NAD<sup>+</sup>), has garnered significant attention in recent years for its anti-aging potential. This review comprehensively reviews the metabolic pathways and molecular mechanisms of NMN, comparing the technical characteristics and industrialization prospects of chemical synthesis, microbial fermentation, and enzyme-catalyzed synthesis. The molecular targets and networks of NMN in core aging mechanisms, such as DNA damage repair, mitochondrial function regulation, inflammatory response balance, gut microbiota remodeling, and autophagy pathway activation, are analyzed. The molecular mechanism of NMN in slowing down the aging process through multi-target synergistic effects is elucidated. However, critical issues such as age-stratified dosage modeling, long-term safety, and efficacy of NMN still require in-depth research. This review provides a theoretical basis and research direction for translational research and precise anti-aging strategies of NMN.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"124"},"PeriodicalIF":4.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiogerontologyPub Date : 2025-06-20DOI: 10.1007/s10522-025-10268-1
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
{"title":"Photoaging: UV radiation-induced cGAS-STING signaling promotes the aging process in skin by remodeling the immune network.","authors":"Antero Salminen, Kai Kaarniranta, Anu Kauppinen","doi":"10.1007/s10522-025-10268-1","DOIUrl":"10.1007/s10522-025-10268-1","url":null,"abstract":"<p><p>Excessive exposure of the skin to UV radiaton (UVR) accelerates the aging process and leads to a photoaging state which involves similar pathological alterations to those occurring in chronological aging. UVR exposure, containing both UVA and UVB radiation, triggers cellular senescence and a chronic inflammatory state in skin. UVR promotes oxidative stress and a leakage of double-stranded DNA (dsDNA) from nuclei and mitochondria into the cytoplasm of keratinocytes and fibroblasts. It is recognized that cytosolic dsDNA is a specific danger signal which stimulates cytoplasmic DNA sensors. The activation of the signaling through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) is a major defence and survival mechanism combatting against tissue injuries. There is abundant evidence that UVR exposure of skin stimulates cGAS-STING signaling which promotes cellular senescence and remodels both the local and systemic immune network. cGAS-STING signaling activates the IRF3 and NF-κB signaling pathways which trigger both pro-inflammatory and immunosuppressive responses. Moreover, cGAS-STING signaling stimulates inflammatory responses by activating the NLRP3 inflammasomes. Senescent fibroblasts secrete not only cytokines but also chemokines and colony-stimulating factors which induce myeloid differentiation and recruitment of immune cells into inflamed skin. Photoaging is associated with an immunosuppressive state in skin which is attributed to an expansion of immunosuppressive cells, such as Tregs. UVR-induced cGAS-STING signaling also stimulates the expression of PD-L1, a ligand for inhibitory immune checkpoint receptor, which evokes an exhaustion of effector immune cells. There is clear evidence that cGAS-STING signaling can also accelerate chronological aging by remodeling the immune network.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"123"},"PeriodicalIF":4.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiogerontologyPub Date : 2025-06-20DOI: 10.1007/s10522-025-10263-6
Chenghui Yu, Xingxing Qiu, Si Tao, Yuanyuan Wu, Siyao He, Qiao Wang, Duozhuang Tang, Yiting Wang
{"title":"The impact of dietary restriction on transcriptional profiles of hematopoietic stem cells in aged female mice.","authors":"Chenghui Yu, Xingxing Qiu, Si Tao, Yuanyuan Wu, Siyao He, Qiao Wang, Duozhuang Tang, Yiting Wang","doi":"10.1007/s10522-025-10263-6","DOIUrl":"10.1007/s10522-025-10263-6","url":null,"abstract":"<p><p>This study investigates the impact of dietary restriction (DR) on gene expression in hematopoietic stem cells (HSCs) derived from aged mice. RNA sequencing (RNA-seq) data were obtained from sorted HSCs, followed by weighted gene co-expression network analysis (WGCNA) to identify differentially expressed genes (DEGs) and key transcriptional modules. Principal component analysis (PCA) and heatmaps revealed significant differences between the groups, highlighting a predominant upregulation of gene expression during aging and a more suppressive gene expression profile under DR. Functional enrichment analysis indicated that the aging process in HSCs is characterized by enhanced expression of genes associated with inflammatory responses and DNA damage, whereas DR significantly reduced gene expression related to immune responses, protein quality control, and cellular stress responses. Additionally, our analysis identified key transcription factors (TFs), such as Gata2, Klf16, and Runx3, which likely mediate the gene expression changes observed under DR. These TFs are implicated in critical processes, including signal transduction, transcriptional regulation, and cellular responses to DNA damage. Furthermore, machine learning algorithms identified Gnptg as a key hub gene associated with programmed cell death (PCD) in HSC aging with its gene products maintaining lysosomal homeostasis. DR reduced lysosomal numbers and preserved lysosomal membrane integrity in aging HSCs, suggesting that lysosomal dysfunction contributes to HSC aging. Overall, DR induces a distinct transcriptional landscape in aged HSCs, suggesting a protective role by reducing harmful gene expression linked to inflammation, DNA damage, apoptosis, and stress responses, thereby maintaining HSC function during aging.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"122"},"PeriodicalIF":4.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiogerontologyPub Date : 2025-06-18DOI: 10.1007/s10522-025-10265-4
Adiv A Johnson, Maxim N Shokhirev
{"title":"First-generation versus next-generation epigenetic aging clocks: Differences in performance and utility.","authors":"Adiv A Johnson, Maxim N Shokhirev","doi":"10.1007/s10522-025-10265-4","DOIUrl":"https://doi.org/10.1007/s10522-025-10265-4","url":null,"abstract":"<p><p>Aging biomarkers that predict age given methylomic data are referred to as epigenetic aging clocks. While the earliest, first-generation clocks were exclusively trained to predict chronological age, more recent next-generation models have been explicitly trained to associate with health, lifestyle, and/or age-related outcomes. Although these next-generation models have been trained using distinct approaches and techniques, existing evidence indicates that they associate with a greater number of health and disease signals than first-generation clocks. Moreover, they are often more predictive of age-related outcomes and appear more responsive to interventions. In this work, we provide definitions for first- versus next-generation clocks and discuss the potential merits of further dividing next-generation clocks into sub-categories. In addition, we summarize existing next-generation epigenetic aging clocks, including how they were trained and how they can be accessed. Given the relative value of interventional data over observational data, we comprehensively tabulate existing literature documenting the ability of an intervention to influence at least one epigenetic aging clock. While we acknowledge that the decision to a use a specific clock is ultimately dependent on the research application and goal, current evidence suggests that next-generation models should be generally prioritized for health-oriented association and interventional studies.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"121"},"PeriodicalIF":4.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiogerontologyPub Date : 2025-06-18DOI: 10.1007/s10522-025-10262-7
Xu He, Yan Li, Jun Chen, Yan Huang, Ying Zhou, Yang Li, Jing Quan
{"title":"β-hydroxy-β-methylbutyrate supplementation mitigates muscle atrophy induced by inactivity and protein deprivation.","authors":"Xu He, Yan Li, Jun Chen, Yan Huang, Ying Zhou, Yang Li, Jing Quan","doi":"10.1007/s10522-025-10262-7","DOIUrl":"10.1007/s10522-025-10262-7","url":null,"abstract":"<p><p>Muscle atrophy, resulting from physical inactivity or protein deficiency, is a significant health concern. β-hydroxy-β-methylbutyrate (HMB) has potential in preserving muscle mass, but its mechanisms in various atrophy-inducing conditions are not fully understood. This study aimed to investigate HMB's effects on muscle atrophy induced by inactivity and protein deprivation, and to elucidate the underlying molecular mechanisms. Rats were subjected to inactivity or protein-deficient diets with or without HMB supplementation. Muscle morphology, strength, and biochemical parameters were assessed. In vitro studies using C2C12 myoblasts and mouse skeletal muscle satellite cells exposed to interleukin-6 (IL-6) explored molecular pathways involved in HMB's protective effects. Inactivity and protein deprivation led to muscle atrophy, reduced strength, and altered biochemical markers. HMB supplementation partially mitigated these effects, preserving muscle mass and function. HMB attenuated atrophy markers (Muscle Atrophy F-box and Muscle RING Finger 1 (MuRF1)) and maintained myogenic factor (Myogenin (MyoG)) levels. In vitro studies revealed that HMB's protective effects were mediated through the AKT/mTOR pathway, with concurrent regulation of autophagy pathways and preservation of mitochondrial function in both myoblasts and satellite cells. HMB specifically protected satellite cell viability and function through AKT-dependent mechanisms, maintaining protein synthesis and reducing apoptosis under IL-6-induced stress conditions. HMB supplementation shows protective effects against muscle atrophy induced by inactivity and protein deprivation, through multiple mechanisms including AKT/mTOR pathway activation, autophagy regulation, and maintenance of mitochondrial function in both myoblasts and satellite cells. These findings suggest HMB as a potential therapeutic strategy for preventing muscle atrophy in various clinical scenarios.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 4","pages":"120"},"PeriodicalIF":4.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}