Biogerontology最新文献

{"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}

{"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}

{"title":"Identifying a gene signature for age-related hearing loss through machine learning and revealing the effect of the CTSS on the mice cochlea.","authors":"Xu Jiang, Jing Ke, Yiting Liu, Xiaoqin Luo, Menglong Feng, Hailan Mo, Wei Yuan","doi":"10.1007/s10522-025-10261-8","DOIUrl":"10.1007/s10522-025-10261-8","url":null,"abstract":"<p><p>Age-related hearing loss (ARHL) is one of the most common health conditions among the elderly population. This study used machine learning to screen for a gene signature to predicts ARHL. Four ARHL mice cochlear transcriptome datasets and the mRNA sequencing of C57BL/6J mice were used for analysis. Machine learning was used to screen for gene signatures closely related to ARHL and validate them. Via qPCR, immunohistochemistry, and immunofluorescence confocal microscopy were used to assess the effect of key gene on the cochlea. The gene signature consisting of 38 genes constructed via Stepglm [forwards] had the best accuracy in the training group, with excellent accuracy and recall in the training and testing groups in predicting ARHL. The gene signature reflected active immune function. CTSS was selected as a key gene on the basis of its association with age and influence hearing loss severity. CTSS showed high expression in ARHL and enriched in the cochlear stria vascularis, which is significantly positively correlated with macrophage marker CD68 expression (R = 0.74, p = 0.006). The gene signature has good accuracy in predicting ARHL. CTSS is highly expressed in the cochleae of ARHL mice and may promote ARHL by inducing macrophage enrichment and causing low-grade inflammation.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 3","pages":"119"},"PeriodicalIF":4.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214727","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":"Bidirectional upregulation of Klotho by triiodothyronine and baicalein: mitigating chronic kidney disease and associated complications in aged BALB/c mice.","authors":"Saswat Kumar Mohanty, Vikas Kumar Sahu, Bhanu Pratap Singh, Kitlangki Suchiang","doi":"10.1007/s10522-025-10257-4","DOIUrl":"10.1007/s10522-025-10257-4","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a global health challenge marked by progressive renal decline and increased mortality. The interplay between CKD and hypothyroidism, particularly nonthyroidal low-triiodothyronine (T3) syndrome, exacerbates disease progression, driven by HPT axis dysfunction and reduced Klotho levels due to the Wnt/β-catenin pathway activation. This study explored Klotho as a link between CKD and hypothyroidism using an adenine-induced CKD aged mouse model. Exogenous T3 and baicalein (BAI), targeting the Wnt pathway, were used to upregulate Klotho expression. Combined T3 and BAI treatment significantly increased Klotho levels, surpassing individual effects, and suppressed key signaling molecules (TGF, NFκB, GSK3), mitigating renal fibrosis and CKD complications, including cardiovascular disorders and dyslipidemia. This bidirectional approach, enhancing Klotho via T3 and sustained Wnt pathway inhibition, offers a novel and effective strategy for CKD management, particularly in elderly patients with hypothyroidism.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 3","pages":"114"},"PeriodicalIF":4.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141425","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":"Reproduction and preference to macronutrients have different relations to biological or chronological age in Drosophila.","authors":"Oleh Lushchak, Olha Strilbytska, Pavlo Petakh, Oleksandr Kamyshnyi, Oleksandr Koliada, Uliana Semaniuk","doi":"10.1007/s10522-025-10259-2","DOIUrl":"10.1007/s10522-025-10259-2","url":null,"abstract":"<p><p>Varied factors and interventions were shown to extend the lifespan. An understanding of the mechanisms behind the beneficial effects might extend our understanding of how interventions work. However, in most studies, groups are compared at distinct time points representing chronological age. This setup does not take into account that organisms of the same chronological age are different biologically. In other words, they have a different biological age that reflects varied physiological traits. We have compared reproduction and consumption of specific macronutrients for flies in according quartiles (Q) of chronological and biological age. Quartiles of chronological age were obtained by dividing the total lifespan of the cohort into 4 parts. Quartiles of biological age were estimated as time points of 75, 50, 25 and 0% survival of the cohort. We found that the decline in carbohydrate or protein consumption was stronger in the case of chronological rather than biological age. However, flies of biological or chronological quartile 4 consumed virtually the same amounts of macronutrients. The decline in reproduction was significantly reduced in relation to biological age. Thus, the decline was about 38-68% when within chronological quartiles 2 and 1 but only 4-31% for biological ones. The reproductive capacity was reduced by 86-93% in flies of chronological Q4 as compared to a 60-77% decrease for those of biological. Starting from quartile 2 biologically aged flies laid significantly higher number of eggs than flies of the same chronological quartile. Our results point out the significant difference in flies of the same biological and chronological quartile and raise the question about the suitability of comparison traits of organisms with different lifespans same chronological age.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 3","pages":"116"},"PeriodicalIF":4.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141427","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":"Vascular senescence and aging: mechanisms, clinical implications, and therapeutic prospects.","authors":"Aitor Picos, Nuria Seoane, Manuel Campos-Toimil, Dolores Viña","doi":"10.1007/s10522-025-10256-5","DOIUrl":"10.1007/s10522-025-10256-5","url":null,"abstract":"<p><p>The aging vasculature is characterized by endothelial dysfunction, arterial stiffness, and increased susceptibility to vascular pathologies. Central to these changes is the process of cellular senescence, where endothelial and vascular smooth muscle cells lose their replicative and functional capacity and adopt a pro-inflammatory secretory phenotype. This review provides an overview of the key mechanisms underlying vascular senescence, including the p53/p21 and p16/Rb pathways, the senescence-associated secretory phenotype (SASP), and oxidative stress, examines its contribution to cardiovascular diseases in older adults, and highlights emerging therapeutic strategies aimed at delaying or reversing these age-related vascular changes. In vascular cells, DNA damage, oxidative stress, and chronic inflammation associated with aging converge to amplify senescence. Clinically, vascular senescence is linked with hypertension, atherosclerosis, and increased overall cardiovascular risk. Several interventions, ranging from senolytics to lifestyle factors, show promise in mitigating these changes; however, long-term studies are needed. Given that vascular senescence is a pivotal driver of cardiovascular pathology in aging, targeting senescent cells or their secretory phenotype may potentially offer new avenues for preventing or attenuating age-related vascular diseases. This review presents an updated and integrative overview of vascular senescence, connecting fundamental cellular mechanisms with their clinical manifestations and highlighting the most promising therapeutic interventions.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 3","pages":"118"},"PeriodicalIF":4.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141012","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":"Therapeutic potential of young plasma in reversing age-related liver inflammation via modulation of NLRP3 inflammasome and necroptosis.","authors":"Burcu Baba, Taha Ceylani, Hikmet Taner Teker, Seda Keskin, Aysun Inan Genc, Rafig Gurbanov, Eda Acikgoz","doi":"10.1007/s10522-025-10260-9","DOIUrl":"10.1007/s10522-025-10260-9","url":null,"abstract":"<p><p>The phenomenon of inflammaging, characterized by an increase in low-grade chronic inflammation, is closely associated with diseases related to liver dysfunction. This study investigated daily plasma exchange between 5-week-old and 24-month-old Sprague Dawley rats for 30 days, focusing on protein secondary structures, NLRP3 inflammasome, and necroptosis. Conformation changes in protein secondary structures were identified by infrared spectroscopy-based pattern recognition analysis. Liver biopsies with histochemical and immunohistochemical staining were used to assess molecules associated with inflammation, necroptosis and NLRP3 inflammasome complex. Expression levels of NLRP3 components were determined by qPCR. Enhanced random coils, 3₁₀ helices, β-turns, and loop structures were identified in old rats and young rats with old plasma. Young rats and old rats with young plasma displayed higher α-helices and β-sheet structures. Young rats with old plasma showed increased NLRP3, ASC, caspase-1, IL-1β, and IL-18 mRNA levels, indicating an inflammatory response. Whereas old rats with young plasma exhibited lower inflammation levels. Histological evaluations revealed that young rats receiving aged plasma showed significantly increased levels of NLRP3, ASC, caspase-1, IL-1β, TNF-α, VEGFR2, RIPK1, and MLKL immunoreactivity, whereas decreased immunoreactivity in aged rats receiving young plasma. These findings suggest that young plasma reduces NLRP3 inflammasome activation and necroptosis in aged rats.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 3","pages":"117"},"PeriodicalIF":4.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140984","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":"The age-dependent impacts of treadmill exercise on cognitive impairments by reducing inflammation and oxidative stress in the hippocampus of morphine-exposed rats: the role of SIRTs 3 &4 and BDNF.","authors":"Saeedeh Ahmadi Nejad, Mohammad Amin Rajizadeh, Saeedeh Shojaeepour, Shahrzad Azizi, Omid Moradnejad, Tania Dehesh, Faezeh Akhgarandouz, Mansoureh Sabzalizadeh, Atena Alifarsangi","doi":"10.1007/s10522-025-10255-6","DOIUrl":"10.1007/s10522-025-10255-6","url":null,"abstract":"<p><p>Morphine addiction has many side effects, such as cognitive disorders. On the other hand, old age alone is one of the risk factors for cognitive decline and can increase the risk of addiction. On the other hand, the positive effects of exercise as a non-pharmacological intervention on cognitive disorders have been shown through the increase of growth factors and synaptic proteins. This study will investigate the impacts of exercise on the consequences of morphine addiction in aged rats, relying on the role of oxidative and inflammatory factors as well as SIRT 3, SIRT 4, and BDNF. 56 male Wistar rats were allotted in 8 groups, 4 for young and 4 for old rats.The groups include 1. Control; 2. Exercise; 3. Morphine exposed; 4. Morphine exposed + Exercise.The rats in morphine-exposed groups received morphine for 21 days, and the rats performed treadmill exercises for 4 weeks. The behavioral tests included Morris water maze (MWM), Open field test (OFT), Elevated plus maze (EPM), and Novel object recognition test (NOR), which were done to evaluate cognitive function. The gene expression of TNF, IL-6, BDNF, SIRT 3, and SIRT 4 was measured in the hippocampus tissue by RT-PCR. Also, the levels of MDA, TAC, SOD and GPX were assessed using by related kits. Our results showed that morphine exposure in both young and old rats resulted in cognitive impairments and increased anxiety-like behaviors. Also, morphine exposure reduced BDNF, SIRT1, and SIRT4 and increased TNF and IL-6 gene expression in the hippocampus of rats. However, exercise could improve cognitive impairments and anxiety in both young and old rats and reduce TNF, IL-6, and MDA and elevation of BDNF, SIRT 3, and SIRT 4 gene expression and TAC, SOD, and GPX levels in the hippocampus tissue. Exercise could improve cognitive impairments following morphine exposure in young and old rats by reducing inflammation and oxidative stress and increasing expression of BDNF, SIRT 3, and SIRT 4.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 3","pages":"113"},"PeriodicalIF":4.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141428","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":"Blood-based biomarkers in centenarians and non-centenarians: a matched, population-based retrospective cohort study using primary care records in Catalonia, Spain.","authors":"Manuel A Moreno, Josep Vidal-Alaball, Marc Saez, Maria A Barceló","doi":"10.1007/s10522-025-10258-3","DOIUrl":"10.1007/s10522-025-10258-3","url":null,"abstract":"<p><p>The global increase in life expectancy has sparked growing interest in the factors that contribute to exceptional longevity. Between 1990 and 2015, the number of centenarians worldwide more than quadrupled. This study aimed to analyse the relationship between blood-based biomarkers and the likelihood of reaching 100 years of age in Catalonia (2015-2022), and to examine how biomarker variations during COVID-19 affected longevity. Using a retrospective cohort study based on primary care electronic health records from Catalonia, we compared centenarians with individuals aged 92 or older who died before reaching 100 years of age. We analysed anaemia, cholesterol, glycemia, kidney function, and liver function biomarkers. We employed multiple strategies to control for confounding including matching without replacement, adjusting for both observed confounders at both the individual and contextual level, and unobserved confounders, in particular spatial dependence. Our findings reveal that centenarians exhibit higher rates of chronic conditions, greater socioeconomic disadvantage, and increased neighbourhood inequality in urban areas. Biologically, longevity was linked to intermediate levels of ferritin and cholesterol, alongside lower glucose, creatinine, and uric acid levels. Glycaemic balance, indicated by HbA1c and fasting glucose, emerged as a key factor in survival to extreme old age. Additionally, biomarker improvements during the pandemic correlated with an increased likelihood of reaching centenarian age. These results emphasize the complex interplay between biological, behavioural, and contextual factors in determining longevity. While biomarkers provide valuable insights, they are insufficient indicators of healthy ageing. Future research should integrate multiple dimensions, among them, environmental, and social determinants for uncovering the mechanisms of longevity.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 3","pages":"115"},"PeriodicalIF":4.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141426","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":"The age-dependent neuroglial interaction with peripheral immune cells in coronavirus-induced neuroinflammation with a special emphasis on COVID-19.","authors":"Satavisha Ghosh, Jayasri Das Sarma","doi":"10.1007/s10522-025-10252-9","DOIUrl":"10.1007/s10522-025-10252-9","url":null,"abstract":"<p><p>Neurodegenerative diseases are chronic progressive disorders that impair memory, cognition, and motor functions, leading to conditions such as dementia, muscle weakness, and speech difficulties. Aging disrupts the stringent balance between pro- and anti-inflammatory cytokines, increasing neuroinflammation, which contributes to neurodegenerative diseases. The aging brain is particularly vulnerable to infections due to a weakened and compromised immune response and impaired integrity of the blood-brain barrier, allowing pathogens like viruses to trigger neurodegeneration. Coronaviruses have been linked to both acute and long-term neurological complications, including cognitive impairments, psychiatric disorders, and neuroinflammation. The virus can induce a cytokine storm, damaging the central nervous system (CNS) and worsening existing neurological conditions. Though its exact mechanism of neuroinvasion remains elusive, evidence suggests it disrupts the blood-brain barrier and triggers immune dysregulation, leading to persistent neurological sequelae in elderly individuals. This review aims to understand the interaction between the peripheral immune system and CNS glial cells in aged individuals, which is imperative in addressing coronavirus-induced neuroinflammation and concomitant neurodegeneration.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 3","pages":"111"},"PeriodicalIF":4.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085717","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}