The interaction between nuclear (nDNA) and mitochondrial DNA (mtDNA) methylation is not well known in the healthy population. The D-loop methylation level of the Olympic champions (N = 58) was significantly lower than that of non-champions (N = 32) (~ 36% unadjusted mean difference p = 0.016, sex and age adjusted p = 0.017). Interestingly, the robust linear analysis revealed that biological sex is a significant factor in mtDNA D-loop methylation (estimate = 1.521, p = 0.033). On the other hand, we cannot find relationships between the methylation levels of mtDNA and nuclear DNA, suggesting distinct regulation of the methylation/demethylation process of mtDNA and nuclear DNA. DNA methylation-based aging clocks showed a significant relationship with the levels of Klotho, irisin, and its receptor (irisin receptor integrin alpha-V), as well as with epigenetic regulators such as ten-eleven translocation enzyme 2, which were measured using enzyme-linked immunosorbent assay. Therefore, the data suggest a complex regulatory process of epigenetic aging and raise the possibility that D-loop methylation may have functional relevance in health, which remains to be explored.
{"title":"Epigenetic insights of Olympic champions: nuclear and mitochondrial DNA methylation and regulators of aging.","authors":"Timea Teglas,Ferenc Torma,Zoltan Bori,Dora Aczel,Gergely Babszky,Takuji Kawamura,Mitsuru Higuchi,Gu Yaodong,Muhammad Lee,Steve Horvath,Zsolt Radak","doi":"10.1007/s11357-025-02092-9","DOIUrl":"https://doi.org/10.1007/s11357-025-02092-9","url":null,"abstract":"The interaction between nuclear (nDNA) and mitochondrial DNA (mtDNA) methylation is not well known in the healthy population. The D-loop methylation level of the Olympic champions (N = 58) was significantly lower than that of non-champions (N = 32) (~ 36% unadjusted mean difference p = 0.016, sex and age adjusted p = 0.017). Interestingly, the robust linear analysis revealed that biological sex is a significant factor in mtDNA D-loop methylation (estimate = 1.521, p = 0.033). On the other hand, we cannot find relationships between the methylation levels of mtDNA and nuclear DNA, suggesting distinct regulation of the methylation/demethylation process of mtDNA and nuclear DNA. DNA methylation-based aging clocks showed a significant relationship with the levels of Klotho, irisin, and its receptor (irisin receptor integrin alpha-V), as well as with epigenetic regulators such as ten-eleven translocation enzyme 2, which were measured using enzyme-linked immunosorbent assay. Therefore, the data suggest a complex regulatory process of epigenetic aging and raise the possibility that D-loop methylation may have functional relevance in health, which remains to be explored.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"29 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-17DOI: 10.1007/s11357-025-02076-9
Menno Van Damme,Sanne Stegen,Bram Steenwinckel,Helene Schroé,Gustavo A Reyes Del Paso,Matias M Pulopulos,Rudi De Raedt,Marie-Anne Vanderhasselt,Wim Derave,Femke Ongenae,Jan Boone,Wim Van Criekinge,Ernst R Rietzschel,Tim De Meyer
Epigenetic clocks are emerging as promising biomarkers of biological aging, yet their sensitivity to short-term interventions remains unclear. This pilot study investigates whether the GrimAge clock can capture the effects of a 6-month cycling-based endurance exercise training intervention, with cardiorespiratory fitness (VO2 max) and body composition as primary outcomes. We enrolled 42 adults aged 35-65, of whom 38 completed the study and 33 adhered to the protocol (> 66% adherence). Participants demonstrated significant improvements in VO2 max (+ 20%, P < 0.001) and body composition (P < 0.001). High-quality epigenetic data preprocessing yielded highly reproducible GrimAge estimates (< 2 months measurement error), which strongly correlated with chronological age (R2 = 0.86, P < 0.001). On average, GrimAge decreased by 7.44 months relative to the expected trajectory (P = 0.012), reflecting improvements in VO2 max (R2 = 0.27, P = 0.002) but not body composition changes. Notably, GrimAge changes strongly correlated with fluctuations in leukocyte composition, particularly neutrophil fraction (R2 = 0.74, P < 0.001). Adjusting for leukocyte composition improved consistency in GrimAge changes, aligning them with additional intervention outcomes and explaining up to 81% of variance. These findings demonstrate that GrimAge is responsive to short-term endurance training, serving as a meaningful biomarker of improved cardiorespiratory fitness, while also capturing immune system variability. This study supports the use of GrimAge in evaluating longevity interventions and highlights the importance of accounting for leukocyte composition in epigenetic aging research.
表观遗传时钟正在成为生物衰老的有前途的生物标志物，但它们对短期干预的敏感性尚不清楚。本初步研究以心肺功能（最大摄氧量）和身体成分为主要指标，调查GrimAge时钟是否能捕捉6个月周期耐力运动训练干预的效果。我们招募了42名年龄在35-65岁之间的成年人，其中38人完成了研究，33人遵守了方案（bbb66%的依从性）。参与者的最大摄氧量（+ 20%,P < 0.001）和身体成分（P < 0.001）均有显著改善。高质量的表观遗传数据预处理产生了高度可重复的GrimAge估计（< 2个月测量误差），其与实足年龄密切相关（R2 = 0.86, P < 0.001）。平均而言，GrimAge相对于预期轨迹减少了7.44个月（P = 0.012），反映了最大摄氧量的改善（R2 = 0.27, P = 0.002），但没有反映身体成分的变化。值得注意的是，GrimAge变化与白细胞组成，特别是中性粒细胞部分的波动密切相关（R2 = 0.74, P < 0.001）。调整白细胞组成提高了GrimAge变化的一致性，使其与其他干预结果一致，并解释了高达81%的差异。这些发现表明GrimAge对短期耐力训练有反应，作为改善心肺健康的有意义的生物标志物，同时也捕获免疫系统变异性。这项研究支持使用GrimAge来评估长寿干预措施，并强调了在表观遗传衰老研究中考虑白细胞组成的重要性。
{"title":"Epigenetic age deceleration reflects exercise-induced cardiorespiratory fitness improvements.","authors":"Menno Van Damme,Sanne Stegen,Bram Steenwinckel,Helene Schroé,Gustavo A Reyes Del Paso,Matias M Pulopulos,Rudi De Raedt,Marie-Anne Vanderhasselt,Wim Derave,Femke Ongenae,Jan Boone,Wim Van Criekinge,Ernst R Rietzschel,Tim De Meyer","doi":"10.1007/s11357-025-02076-9","DOIUrl":"https://doi.org/10.1007/s11357-025-02076-9","url":null,"abstract":"Epigenetic clocks are emerging as promising biomarkers of biological aging, yet their sensitivity to short-term interventions remains unclear. This pilot study investigates whether the GrimAge clock can capture the effects of a 6-month cycling-based endurance exercise training intervention, with cardiorespiratory fitness (VO2 max) and body composition as primary outcomes. We enrolled 42 adults aged 35-65, of whom 38 completed the study and 33 adhered to the protocol (> 66% adherence). Participants demonstrated significant improvements in VO2 max (+ 20%, P < 0.001) and body composition (P < 0.001). High-quality epigenetic data preprocessing yielded highly reproducible GrimAge estimates (< 2 months measurement error), which strongly correlated with chronological age (R2 = 0.86, P < 0.001). On average, GrimAge decreased by 7.44 months relative to the expected trajectory (P = 0.012), reflecting improvements in VO2 max (R2 = 0.27, P = 0.002) but not body composition changes. Notably, GrimAge changes strongly correlated with fluctuations in leukocyte composition, particularly neutrophil fraction (R2 = 0.74, P < 0.001). Adjusting for leukocyte composition improved consistency in GrimAge changes, aligning them with additional intervention outcomes and explaining up to 81% of variance. These findings demonstrate that GrimAge is responsive to short-term endurance training, serving as a meaningful biomarker of improved cardiorespiratory fitness, while also capturing immune system variability. This study supports the use of GrimAge in evaluating longevity interventions and highlights the importance of accounting for leukocyte composition in epigenetic aging research.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"56 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-16DOI: 10.1007/s11357-025-02078-7
Sagar Vyavahare,Ford Berger,Shelton G Swint,Bharati Mendhe,Mansi Shukla,Ian Duchesne,Roger Zhong,Marion A Cooley,Meghan E McGee-Lawrence,Carlos M Isales,Jessica M Hoffman,Sadanand Fulzele
Aging is associated with alterations in endogenous tryptophan (TRP) metabolism that contributes to musculoskeletal decline. In this study, we investigated the effects of the microbiota-derived TRP metabolite, indole-3-propionic acid (IPA), on musculoskeletal health in aged mice and lifespan in Drosophila melanogaster. Aged C57BL/6 mice received IPA (20 mg/kg, subcutaneous, three times per week for 12 weeks), while Drosophila were maintained on food supplemented with IPA (100 µM) throughout their lifespan. Our findings revealed that IPA-treated aged mice exhibited enhanced muscle function (grip strength and hang time). Histological and bone microCT analyses revealed no changes in muscle fiber size but enhanced bone microarchitecture. Furthermore, molecular studies have elucidated that IPA treatment prevents oxidative stress and reduces senescence, indicating improved cellular survival. Our Drosophila melanogaster longevity analysis revealed a significant extension of lifespan, but lifespan effects were genotype- and sex-specific. Collectively, our findings identify IPA as a promising microbiota-derived metabolite that improves musculoskeletal health and promotes longevity, highlighting its potential as a therapeutic intervention for age-related decline in function.
{"title":"Microbiota-derived indole-3-propionic acid extends lifespan in Drosophila and improves muscle and bone health in mice.","authors":"Sagar Vyavahare,Ford Berger,Shelton G Swint,Bharati Mendhe,Mansi Shukla,Ian Duchesne,Roger Zhong,Marion A Cooley,Meghan E McGee-Lawrence,Carlos M Isales,Jessica M Hoffman,Sadanand Fulzele","doi":"10.1007/s11357-025-02078-7","DOIUrl":"https://doi.org/10.1007/s11357-025-02078-7","url":null,"abstract":"Aging is associated with alterations in endogenous tryptophan (TRP) metabolism that contributes to musculoskeletal decline. In this study, we investigated the effects of the microbiota-derived TRP metabolite, indole-3-propionic acid (IPA), on musculoskeletal health in aged mice and lifespan in Drosophila melanogaster. Aged C57BL/6 mice received IPA (20 mg/kg, subcutaneous, three times per week for 12 weeks), while Drosophila were maintained on food supplemented with IPA (100 µM) throughout their lifespan. Our findings revealed that IPA-treated aged mice exhibited enhanced muscle function (grip strength and hang time). Histological and bone microCT analyses revealed no changes in muscle fiber size but enhanced bone microarchitecture. Furthermore, molecular studies have elucidated that IPA treatment prevents oxidative stress and reduces senescence, indicating improved cellular survival. Our Drosophila melanogaster longevity analysis revealed a significant extension of lifespan, but lifespan effects were genotype- and sex-specific. Collectively, our findings identify IPA as a promising microbiota-derived metabolite that improves musculoskeletal health and promotes longevity, highlighting its potential as a therapeutic intervention for age-related decline in function.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"29 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metacontrol, the ability to adapt cognitive control to task demands, declines with age and is thought to be reflected in aperiodic and periodic neural dynamics. Given that anodal transcranial direct current stimulation (atDCS) can modulate cortical excitability via membrane potential shifts, we tested whether atDCS alters the neurophysiological signatures of metacontrol in younger and older adults. In a mixed design, younger and older participants performed a Go/Nogo task under both atDCS and sham stimulation conditions; resting-state EEG data were also acquired. Aperiodic activity was analyzed using the FOOOF algorithm, and periodic activity was examined through time-frequency analysis. Behaviorally, younger adults showed higher accuracy and faster responses than older adults, but no significant stimulation effects emerged in either group. Results showed that, compared to sham, aperiodic activity (FOOOF exponent) increased after atDCS, particularly in older adults, indicating a steepening of the EEG spectrum and thus increased inhibitory tone in the aging process. However, resting-state aperiodic activity did not predict stimulation-induced effects within either group. In the periodic domain, we found no evidence that atDCS modulated task-related theta or alpha power. Moreover, exploratory analyses revealed no significant associations between atDCS-induced changes in the aperiodic exponent and oscillatory power. This dissociation indicates that, under the present conditions, the periodic and aperiodic components of the EEG signal reflect distinct and likely independent neurophysiological responses to neuromodulation. Targeting metacontrol mechanisms through neuromodulation may, with further validation, open new avenues for supporting cognitive health in older adults.
{"title":"Metacontrol-related aperiodic and periodic neural activity in cognitive aging: enhancing the neural signal-to-noise ratio through anodal transcranial direct current stimulation.","authors":"Yu Pi,Qinfei Zhang,Shuhui Lyu,Christian Beste,Lorenza Colzato,Bernhard Hommel","doi":"10.1007/s11357-025-02077-8","DOIUrl":"https://doi.org/10.1007/s11357-025-02077-8","url":null,"abstract":"Metacontrol, the ability to adapt cognitive control to task demands, declines with age and is thought to be reflected in aperiodic and periodic neural dynamics. Given that anodal transcranial direct current stimulation (atDCS) can modulate cortical excitability via membrane potential shifts, we tested whether atDCS alters the neurophysiological signatures of metacontrol in younger and older adults. In a mixed design, younger and older participants performed a Go/Nogo task under both atDCS and sham stimulation conditions; resting-state EEG data were also acquired. Aperiodic activity was analyzed using the FOOOF algorithm, and periodic activity was examined through time-frequency analysis. Behaviorally, younger adults showed higher accuracy and faster responses than older adults, but no significant stimulation effects emerged in either group. Results showed that, compared to sham, aperiodic activity (FOOOF exponent) increased after atDCS, particularly in older adults, indicating a steepening of the EEG spectrum and thus increased inhibitory tone in the aging process. However, resting-state aperiodic activity did not predict stimulation-induced effects within either group. In the periodic domain, we found no evidence that atDCS modulated task-related theta or alpha power. Moreover, exploratory analyses revealed no significant associations between atDCS-induced changes in the aperiodic exponent and oscillatory power. This dissociation indicates that, under the present conditions, the periodic and aperiodic components of the EEG signal reflect distinct and likely independent neurophysiological responses to neuromodulation. Targeting metacontrol mechanisms through neuromodulation may, with further validation, open new avenues for supporting cognitive health in older adults.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"4 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dysregulation in lipid metabolism is increasingly recognized as a key contributor to age-related diseases, including neurodegeneration and cerebrovascular dysfunction. While prior studies have largely focused on glial cells, the impact of lipid dysregulation on brain endothelial aging remains poorly understood. In this study, we conducted a secondary analysis of single-cell transcriptomic data from young and aged mouse brains, with a specific focus on endothelial cells (ECs). Our analyses revealed that aging promotes lipid droplet accumulation in brain ECs. These lipid-laden brain ECs exhibit a transcriptomic signature indicative of impaired blood-brain barrier function, increased cellular senescence, and inflammation in aging. Furthermore, lipid accumulation is associated with an altered metabolic phenotype characterized by increased fatty acid oxidation and decreased glycolysis and impaired mitochondrial electron transport chain activity in the ECs of the aging brain. We have also validated lipid accumulation in aged ECs in vivo. Collectively, our findings indicate that lipid accumulation may drive structural, functional, and metabolic impairments in the brain ECs, likely contributing to cerebrovascular aging. Understanding the mechanisms underlying lipid accumulation-induced endothelial dysfunction may offer novel therapeutic strategies for mitigating microvascular dysfunction and cognitive decline in aging.
{"title":"Lipid-laden endothelial cells exhibit a transcriptomic signature linked to blood-brain barrier dysfunction, metabolic reprogramming, and increased inflammation in the aging brain.","authors":"Sarah Otu-Boakye, Duraipandy Natarajan, Bhuvana Plakkot, Ilakiya Raghavendiran, Paulina Hoppa, Tamas Kiss, Madhan Subramanian, Priya Balasubramanian","doi":"10.1007/s11357-025-01986-y","DOIUrl":"10.1007/s11357-025-01986-y","url":null,"abstract":"<p><p>Dysregulation in lipid metabolism is increasingly recognized as a key contributor to age-related diseases, including neurodegeneration and cerebrovascular dysfunction. While prior studies have largely focused on glial cells, the impact of lipid dysregulation on brain endothelial aging remains poorly understood. In this study, we conducted a secondary analysis of single-cell transcriptomic data from young and aged mouse brains, with a specific focus on endothelial cells (ECs). Our analyses revealed that aging promotes lipid droplet accumulation in brain ECs. These lipid-laden brain ECs exhibit a transcriptomic signature indicative of impaired blood-brain barrier function, increased cellular senescence, and inflammation in aging. Furthermore, lipid accumulation is associated with an altered metabolic phenotype characterized by increased fatty acid oxidation and decreased glycolysis and impaired mitochondrial electron transport chain activity in the ECs of the aging brain. We have also validated lipid accumulation in aged ECs in vivo. Collectively, our findings indicate that lipid accumulation may drive structural, functional, and metabolic impairments in the brain ECs, likely contributing to cerebrovascular aging. Understanding the mechanisms underlying lipid accumulation-induced endothelial dysfunction may offer novel therapeutic strategies for mitigating microvascular dysfunction and cognitive decline in aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1007/s11357-025-02072-z
Nan Hua,Ruth Harris,Shalini Ahuja,Xiangmin Tan,Kia-Chong Chua,Yihan Mo,Joanne M Fitzpatrick
Group dance is an engaging physical activity that may benefit the prevention and management of sarcopenia among older adults. However, current evidence on this topic is limited. We aimed to evaluate published evidence on group dance for sarcopenia in community dwelling older adults. Studies published in English and Chinese between 2014 and 2024 were identified through searches in MEDLINE, Embase, and PsycINFO via Ovid, CINAHL via EBSCO, Chinese National Knowledge Infrastructure, Wan Fang, Google Scholar, and Web of Science Core Collection. Two reviewers independently performed screening, data extraction, and risk of bias assessment. Quantitative data were meta-analysed, and qualitative findings were analysed using thematic analysis. The protocol was registered with PROSPERO (CRD42024554152). 24 studies were included, comprising 1840 participants across 12 countries and involving nine types of group dance interventions. Meta-analysis showed significant improvements in the Short Physical Performance Battery (MD = 1.32, 95%CI: 0.56, 2.08, I2 = 37%), Sit and Reach Test (MD = 1.91, 95%CI: 0.29, 2.91, I2 = 0), Montreal Cognitive Assessment (MD = 0.94, 95%CI: 0.01, 1.87, I2 = 0) and Trail Making Test (SMD = 0.12, 95%CI: 0.03, 0.21, I2 = 34%). No significant differences were observed in muscle strength, 5 times Sit-To-Stand, Time Up and Go, Single Leg Test, 30s Chair Stand, and gait speed. Qualitative analysis identified three overarching themes: psychosocial, physical, and cognitive wellbeing. Group dance is a safe, acceptable, and promising community intervention that improves physical performance in older adults. Enjoyment-driven and socially engaging group dance interventions are encouraged to support the prevention and management of sarcopenia. Future investigation should use sarcopenia-specific assessments, and consider cultural context, baseline physical status, and individual preferences when designing and evaluating group dance interventions.
{"title":"Group dance interventions for community dwelling older adults to prevent and treat sarcopenia: a mixed methods systematic review.","authors":"Nan Hua,Ruth Harris,Shalini Ahuja,Xiangmin Tan,Kia-Chong Chua,Yihan Mo,Joanne M Fitzpatrick","doi":"10.1007/s11357-025-02072-z","DOIUrl":"https://doi.org/10.1007/s11357-025-02072-z","url":null,"abstract":"Group dance is an engaging physical activity that may benefit the prevention and management of sarcopenia among older adults. However, current evidence on this topic is limited. We aimed to evaluate published evidence on group dance for sarcopenia in community dwelling older adults. Studies published in English and Chinese between 2014 and 2024 were identified through searches in MEDLINE, Embase, and PsycINFO via Ovid, CINAHL via EBSCO, Chinese National Knowledge Infrastructure, Wan Fang, Google Scholar, and Web of Science Core Collection. Two reviewers independently performed screening, data extraction, and risk of bias assessment. Quantitative data were meta-analysed, and qualitative findings were analysed using thematic analysis. The protocol was registered with PROSPERO (CRD42024554152). 24 studies were included, comprising 1840 participants across 12 countries and involving nine types of group dance interventions. Meta-analysis showed significant improvements in the Short Physical Performance Battery (MD = 1.32, 95%CI: 0.56, 2.08, I2 = 37%), Sit and Reach Test (MD = 1.91, 95%CI: 0.29, 2.91, I2 = 0), Montreal Cognitive Assessment (MD = 0.94, 95%CI: 0.01, 1.87, I2 = 0) and Trail Making Test (SMD = 0.12, 95%CI: 0.03, 0.21, I2 = 34%). No significant differences were observed in muscle strength, 5 times Sit-To-Stand, Time Up and Go, Single Leg Test, 30s Chair Stand, and gait speed. Qualitative analysis identified three overarching themes: psychosocial, physical, and cognitive wellbeing. Group dance is a safe, acceptable, and promising community intervention that improves physical performance in older adults. Enjoyment-driven and socially engaging group dance interventions are encouraged to support the prevention and management of sarcopenia. Future investigation should use sarcopenia-specific assessments, and consider cultural context, baseline physical status, and individual preferences when designing and evaluating group dance interventions.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"26 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aging is accompanied by cumulative oxidative stress that promotes tissue degeneration and reproductive decline. Here, we show that deficiency of superoxide dismutase 1 (SOD1) accelerates oxidative injury and reproductive aging through a ferroptosis-linked redox imbalance, and that ginseng root extract (GR) confers protection across species. Aged hairless Sod1⁻/⁻ mice exhibited markedly elevated skin and plasma oxidative stress markers-including 8-isoprostane, malondialdehyde (MDA), and pentosidine-together with dermal cyst formation and atrophic pathology. Complementary studies in C. elegans revealed that SOD1-deficient strains displayed increased reactive oxygen species, depleted glutathione, and elevated iron and lipid peroxidation-canonical features of ferroptosis-associated oxidative stress. These redox alterations coincided with shortened reproductive span and reduced progeny output, both rescued by ferroptosis inhibition or GR supplementation. In female Sod1⁻/⁻ mice, GR restored folliculogenesis, normalized estrous cyclicity, and improved ovarian morphology. Collectively, these findings identify SOD1 loss as a driver of ferroptosis-associated oxidative and reproductive aging and highlight GR as a promising redox-targeted intervention.
{"title":"SOD1 deficiency drives ferroptosis-linked oxidative and reproductive aging, mitigated by ginseng root extract.","authors":"Juewon Kim,Shuichi Shibuya,Yusuke Ozawa,Yorino Sato,Kazuhiro Kawamura,Takahiko Shimizu","doi":"10.1007/s11357-025-02093-8","DOIUrl":"https://doi.org/10.1007/s11357-025-02093-8","url":null,"abstract":"Aging is accompanied by cumulative oxidative stress that promotes tissue degeneration and reproductive decline. Here, we show that deficiency of superoxide dismutase 1 (SOD1) accelerates oxidative injury and reproductive aging through a ferroptosis-linked redox imbalance, and that ginseng root extract (GR) confers protection across species. Aged hairless Sod1⁻/⁻ mice exhibited markedly elevated skin and plasma oxidative stress markers-including 8-isoprostane, malondialdehyde (MDA), and pentosidine-together with dermal cyst formation and atrophic pathology. Complementary studies in C. elegans revealed that SOD1-deficient strains displayed increased reactive oxygen species, depleted glutathione, and elevated iron and lipid peroxidation-canonical features of ferroptosis-associated oxidative stress. These redox alterations coincided with shortened reproductive span and reduced progeny output, both rescued by ferroptosis inhibition or GR supplementation. In female Sod1⁻/⁻ mice, GR restored folliculogenesis, normalized estrous cyclicity, and improved ovarian morphology. Collectively, these findings identify SOD1 loss as a driver of ferroptosis-associated oxidative and reproductive aging and highlight GR as a promising redox-targeted intervention.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"6 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1007/s11357-025-02062-1
Prince Ahad Mir,Nishant Kumar,Gyamcho Tshering Bhutia,Preeti Chaudhary,Gurkiran Kaur,Sukesh Kumar Gupta
Alzheimer's disease (AD), the most common cause of dementia in the aging population, is marked by amyloid-beta (Aβ) plaques, tau tangles, and progressive neuronal degeneration, placing heavy clinical and socioeconomic burdens on healthcare worldwide. Aging remains the strongest risk factor, with chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and impaired proteostasis creating a vulnerable brain environment that accelerates AD onset and progression. Recent evidence highlights the gut-glia-immune axis as a critical pathway linking age-related microbiome changes to glial dysfunction. Microbial metabolites, such as short-chain fatty acids and tryptophan derivatives, regulate microglial maturation, astrocytic activity, and neuroimmune signaling. However, age-associated dysbiosis disrupts glial homeostasis, amplifies neuroinflammation, and impairs amyloid clearance, thereby worsening neurodegeneration. Preclinical models including germ-free mice and fecal microbiota transplantation along with clinical studies of elderly AD patients, provide compelling evidence of microbiome-driven modulation of disease. From a therapeutic perspective, microbiome-targeted interventions including probiotics, prebiotics, synbiotics, and microbiota-directed small molecules offer promising strategies to restore glial balance, reduce inflammation, and protect cognitive function. This review highlights the therapeutic potential of probiotics, synbiotics, and fecal microbiota transplantation for mitigating neuroinflammation and cognitive decline in Alzheimer's disease. However, given the multifactorial nature of neurodegenerative disorders, these strategies are unlikely to be universally effective and must be tailored to individual patient profiles.
{"title":"The aging gut-glia-immune axis in alzheimer's disease: microbiome-derived mediators of neuroinflammation and therapeutic innovation.","authors":"Prince Ahad Mir,Nishant Kumar,Gyamcho Tshering Bhutia,Preeti Chaudhary,Gurkiran Kaur,Sukesh Kumar Gupta","doi":"10.1007/s11357-025-02062-1","DOIUrl":"https://doi.org/10.1007/s11357-025-02062-1","url":null,"abstract":"Alzheimer's disease (AD), the most common cause of dementia in the aging population, is marked by amyloid-beta (Aβ) plaques, tau tangles, and progressive neuronal degeneration, placing heavy clinical and socioeconomic burdens on healthcare worldwide. Aging remains the strongest risk factor, with chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and impaired proteostasis creating a vulnerable brain environment that accelerates AD onset and progression. Recent evidence highlights the gut-glia-immune axis as a critical pathway linking age-related microbiome changes to glial dysfunction. Microbial metabolites, such as short-chain fatty acids and tryptophan derivatives, regulate microglial maturation, astrocytic activity, and neuroimmune signaling. However, age-associated dysbiosis disrupts glial homeostasis, amplifies neuroinflammation, and impairs amyloid clearance, thereby worsening neurodegeneration. Preclinical models including germ-free mice and fecal microbiota transplantation along with clinical studies of elderly AD patients, provide compelling evidence of microbiome-driven modulation of disease. From a therapeutic perspective, microbiome-targeted interventions including probiotics, prebiotics, synbiotics, and microbiota-directed small molecules offer promising strategies to restore glial balance, reduce inflammation, and protect cognitive function. This review highlights the therapeutic potential of probiotics, synbiotics, and fecal microbiota transplantation for mitigating neuroinflammation and cognitive decline in Alzheimer's disease. However, given the multifactorial nature of neurodegenerative disorders, these strategies are unlikely to be universally effective and must be tailored to individual patient profiles.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"2020 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1007/s11357-026-02095-0
Beatrice Polini,Sandra Ghelardoni,Gerarda Capone,Emilia Monti,Grazia Chiellini,Vincenzo Lionetti,Raffaele De Caterina,Rosalinda Madonna
Pulmonary arterial hypertension (PAH) is a rare and progressive and life-threatening clinical condition characterized by elevated mean pulmonary arterial pressure (mPAP ≥ 20 mmHg at rest), increased pulmonary vascular resistance (PVR ≥ 2 Wood units), and normal pulmonary arterial wedge pressure. PAH group 1 comprises idiopathic, heritable, and drug- or toxin-induced forms, as well as cases associated with connective tissue diseases, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, persistent pulmonary hypertension of the newborn, and pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis. The diagnosis of PAH is frequently delayed, and clinical outcomes remain poor in a significant proportion of patients, although several targeted therapies, acting on the endothelin (ET-1), nitric oxide (NO), and prostacyclin pathways, have been developed, and novel agents (i.e., sotatercept) are showing promising results in clinical trials. Circulating microRNAs (miRNAs) have emerged as promising biomarker candidates for risk stratification and prediction of therapeutic response in PAH group 1. These small non-coding RNAs that regulate gene expression at the post-transcriptional level are released into the circulation either actively, via extracellular vesicles such as exosomes and microvesicles, or passively as a result of cell damage. These features confer remarkable stability in biological fluids, making circulating miRNAs particularly attractive not only as innocent bystanders but also as factors actively involved in the pathogenesis of the disease. The aim of this review is to provide an overview of the role of circulating miRNAs in PAH group 1, with a focus on their diagnostic, prognostic, and therapeutic potential.
{"title":"Circulating microRNAs in pulmonary arterial hypertension: biomarkers for diagnosis, prognostic stratification, and treatment.","authors":"Beatrice Polini,Sandra Ghelardoni,Gerarda Capone,Emilia Monti,Grazia Chiellini,Vincenzo Lionetti,Raffaele De Caterina,Rosalinda Madonna","doi":"10.1007/s11357-026-02095-0","DOIUrl":"https://doi.org/10.1007/s11357-026-02095-0","url":null,"abstract":"Pulmonary arterial hypertension (PAH) is a rare and progressive and life-threatening clinical condition characterized by elevated mean pulmonary arterial pressure (mPAP ≥ 20 mmHg at rest), increased pulmonary vascular resistance (PVR ≥ 2 Wood units), and normal pulmonary arterial wedge pressure. PAH group 1 comprises idiopathic, heritable, and drug- or toxin-induced forms, as well as cases associated with connective tissue diseases, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, persistent pulmonary hypertension of the newborn, and pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis. The diagnosis of PAH is frequently delayed, and clinical outcomes remain poor in a significant proportion of patients, although several targeted therapies, acting on the endothelin (ET-1), nitric oxide (NO), and prostacyclin pathways, have been developed, and novel agents (i.e., sotatercept) are showing promising results in clinical trials. Circulating microRNAs (miRNAs) have emerged as promising biomarker candidates for risk stratification and prediction of therapeutic response in PAH group 1. These small non-coding RNAs that regulate gene expression at the post-transcriptional level are released into the circulation either actively, via extracellular vesicles such as exosomes and microvesicles, or passively as a result of cell damage. These features confer remarkable stability in biological fluids, making circulating miRNAs particularly attractive not only as innocent bystanders but also as factors actively involved in the pathogenesis of the disease. The aim of this review is to provide an overview of the role of circulating miRNAs in PAH group 1, with a focus on their diagnostic, prognostic, and therapeutic potential.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"129 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1007/s11357-025-02083-w
Daniel W Fisher,Jillian R Fisher,Silvan R Urfer,NhiVan A Tran,Kathleen F Kerr, ,Martin Darvas
Non-cognitive, neuropsychiatric symptoms (NPS) are nearly universal in Alzheimer's disease (AD), but investigation of their underlying biology is complicated by comparative medicine approaches that incompletely capture spontaneous disease, primarily using transgenic rodent models. The aged companion dog, which spontaneously develops an AD-like disease called canine cognitive dysfunction (CCD), may help fill this translational gap. Using data from the Dog Aging Project with > 10,000 aged dogs (> 8 years old), we identify numerous behaviors in dogs "at-risk" for and with CCD that mirror NPS in humans. Compared to dogs without CCD, our analysis shows that dogs with CCD are less physically active, exhibit fewer previously trained behaviors, demonstrate fewer motivated behaviors, have more daytime sleep, demonstrate more separation anxiety, have altered anxious responses to novelty, have changes in aggressive behaviors, and exhibit lower appetite. Using k-means clustering, we did not find evidence for behavioral sub-phenotypes. Overall, our analysis of a large number of aged dogs suggests clinically significant NPS are associated with CCD and that the companion dog may serve as an important comparative medicine approach to understand these debilitating symptoms across species.
{"title":"Higher burden of neuropsychiatric symptom-like behaviors associated with canine cognitive dysfunction compared to normal aging in the Dog Aging Project.","authors":"Daniel W Fisher,Jillian R Fisher,Silvan R Urfer,NhiVan A Tran,Kathleen F Kerr, ,Martin Darvas","doi":"10.1007/s11357-025-02083-w","DOIUrl":"https://doi.org/10.1007/s11357-025-02083-w","url":null,"abstract":"Non-cognitive, neuropsychiatric symptoms (NPS) are nearly universal in Alzheimer's disease (AD), but investigation of their underlying biology is complicated by comparative medicine approaches that incompletely capture spontaneous disease, primarily using transgenic rodent models. The aged companion dog, which spontaneously develops an AD-like disease called canine cognitive dysfunction (CCD), may help fill this translational gap. Using data from the Dog Aging Project with > 10,000 aged dogs (> 8 years old), we identify numerous behaviors in dogs \"at-risk\" for and with CCD that mirror NPS in humans. Compared to dogs without CCD, our analysis shows that dogs with CCD are less physically active, exhibit fewer previously trained behaviors, demonstrate fewer motivated behaviors, have more daytime sleep, demonstrate more separation anxiety, have altered anxious responses to novelty, have changes in aggressive behaviors, and exhibit lower appetite. Using k-means clustering, we did not find evidence for behavioral sub-phenotypes. Overall, our analysis of a large number of aged dogs suggests clinically significant NPS are associated with CCD and that the companion dog may serve as an important comparative medicine approach to understand these debilitating symptoms across species.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"30 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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