GeroScience最新文献

{"title":"Effects of life-long hyperlipidaemia on age-dependent development of endothelial dysfunction in humanised dyslipidaemic mice","authors":"Anna Bar, Piotr Berkowicz, Anna Kurpinska, Tasnim Mohaissen, Agnieszka Karaś, Patrycja Kaczara, Joanna Suraj-Prażmowska, Magdalena Sternak, Brygida Marczyk, Agata Malinowska, Agnieszka Kij, Agnieszka Jasztal, Izabela Czyzynska-Cichon, Elsbet J. Pieterman, Hans M. G. Princen, Jacek R. Wiśniewski, Stefan Chlopicki","doi":"10.1007/s11357-025-01578-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01578-w","url":null,"abstract":"<p>Little is known, how life-long hyperlipidaemia affects vascular ageing, before atherosclerosis. Here, we characterise effects of mild, life-long hyperlipidaemia on age-dependent endothelial dysfunction (ED) in humanised dyslipidaemia model of E3L.CETP mice. Vascular function was characterised using magnetic resonance imaging in vivo and wire myograph ex vivo. Plasma endothelial biomarkers and non-targeted proteomics in plasma and aorta were analysed. Early atherosclerosis lesions were occasionally present only in 40-week-old or older E3L.CETP mice. However, age-dependent ED developed earlier, in 14-week-old male and 22-week-old female E3L.CETP mice as compared with 40-week-old female and male C57BL/6J mice. Acetylcholine-induced vasodilation in 8-week-old E3L.CETP, especially female mice, was blocked by catalase and attributed to H₂O₂. In 8-week-old female E3L.CETP mice, changes in plasma proteome in response to hyperlipidaemia were modest, while in male mice a number of differentially expressed proteins were identified that were involved in oxidative stress response, inflammation and regulation of metabolic pathways. In contrast, in older E3L.CETP and C57BL/6J mice, either plasma or aortic proteome displayed similar pattern of vascular ageing, dominating over hyperlipidaemia-induced changes. Interestingly, in 48-week-old male but not female E3L.CETP mice, vascular mitochondrial functional response was impaired. Early resilience of hyperlipidaemia-induced detrimental effects in young female E3L.CETP mice on a functional level was associated with a switch in vasodilation mechanism, blunted systemic proteomic response in plasma and slower ED development as compared to male E3L.CETP mice. The results indicate that profile of early vascular response to risk factors in young age may determine level of ED in older age before atherosclerosis development.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"59 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841305","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}

{"title":"Glycation metabolites predict incident age-related comorbidities and mortality in older people with HIV","authors":"Xi Qiao, Liangliang Zhang, Emely A. Hoffman, Grace E. Mastin, Corrilynn O. Hileman, Asha R. Kallianpur, Ming Wang, Ronald J. Ellis, Susan L. Koletar, Frank J. Palella, Katherine K. Tassiopoulos, Alan L. Landay, Pankaj Kapahi, James J. Galligan, Robert C. Kalayjian","doi":"10.1007/s11357-025-01652-3","DOIUrl":"https://doi.org/10.1007/s11357-025-01652-3","url":null,"abstract":"<p>Glycation is a class of modifications arising from non-enzymatic reactions of reducing sugars with proteins, lipids, and/or DNA, generating advanced glycation end-products (AGEs). AGEs are linked to many age-related comorbidities. In response to HIV-1 infection, activated T-cells and macrophages shift their predominate metabolism from oxidative phosphorylation to glycolysis. Increased glycolytic flux enhances AGE formation, which may increase age-related comorbidities. In this prospective, multicenter cohort study of antiretroviral therapy treated people with HIV, we explored predictive associations by baseline plasma AGE concentrations and their corresponding detoxification metabolites, with incident comorbidities and mortality. AGEs included dicarbonyl sugars: 3-deoxyglucosone, glyoxal, and methylglyoxal. Methylglyoxal-derived metabolites included carboxyethyl-arginine, carboxyethyl-lysine, and methylglyoxal hydroimidazolone-1. Detoxification metabolites included reduced and oxidized glutathione, and the glyoxalase cycle products lactoyl-glutathione and lactoyl-Lysine modified proteins. Plasma was collected at study entry, in the fasting state, and assayed by liquid chromatography-mass spectroscopy. Incident clinical outcomes included diabetes, chronic kidney disease, hypertension, neurocognitive impairment, peripheral neuropathy, frailty, fractures, recurrent falls, and all-cause mortality. Among 376 participants, higher baseline plasma concentrations of methylglyoxal derived AGEs predicted increased risks of diabetes, chronic kidney disease, and recurrent falls, while higher 3-deoxyglucosone predicted an increased risk of peripheral neuropathy. By contrast, higher baseline concentrations of reduced or oxidized glutathione, lactoyl-glutathione, and/or lactoyl-Lysine modified proteins predicted lower risks of diabetes, neurocognitive impairment, frailty, fractures, recurrent falls, and all-cause mortality. These findings support growing experimental evidence of the potential to mitigate age-related declines by interventions that reduce glycation or increase glutathione.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"6 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841357","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}

{"title":"Prospective association of depression symptoms with exceptional longevity among older women","authors":"Carlos E. Rosas, Steve Nguyen, Aladdin H. Shadyab, Ariana M. Stickel, Shawnita Sealy-Jefferson, Michelle J. Naughton, Lorena Garcia, Linda C. Gallo, Andrea Z. LaCroix","doi":"10.1007/s11357-025-01659-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01659-w","url":null,"abstract":"<p>Older women may experience elevated depression symptoms, which have been associated with morbidity and mortality. Yet, few studies have examined associations of depression symptoms with longevity. We examined associations among older women of depression symptoms with survival to ages 90, 95, and 100, and survival to age 90 with intact mobility and cognitive functioning. Participants were 70,560 women enrolled in the Women’s Health Initiative with potential, due to birth year, to reach age ≥ 90 as of February 2022. Depression symptoms were assessed at baseline (1993–1998) using the Burnam screen, which comprises the 6-item Center for Epidemiologic Studies Depression Scale and 2 items from the Diagnostic Interview Schedule. Depression symptoms were classified as elevated (vs. not) using an established cut point of ≥ 0.06 for detecting depressive disorders. Survival (vs. death) to ages 90, 95, and 100 years was assessed. Among women surviving to age ≥ 90, maintenance of mobility and cognitive function were assessed in relation to depression symptoms. A total of 37,460 women (53.1%) survived to age ≥ 90. Women with (vs. without) elevated depression symptoms had 15% lower odds of surviving to age 90, 18% lower odds of surviving to age 95, and 23% lower odds of surviving to age 100. Among women surviving to 90, those with (vs. without) elevated depression symptoms had 46% lower odds of surviving with intact mobility and cognition. Depression symptoms associated with lower odds of healthy longevity. Findings underscore importance of depression intervention to increase women’s odds of healthy longevity.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"37 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836695","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}

{"title":"Systemic deficits in lipid homeostasis promote aging-associated impairments in B cell progenitor development","authors":"Silvia Vicenzi, Fangyuan Gao, Parker Côté, Joshua D. Hartman, Lara C. Avsharian, Ashni A. Vora, R. Grant Rowe, Hojun Li, Dorota Skowronska-Krawczyk, Leslie A. Crews","doi":"10.1007/s11357-025-01594-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01594-w","url":null,"abstract":"<p>Organismal aging has been associated with diverse metabolic and functional changes across tissues. Within the immune system, key features of physiological hematopoietic cell aging include increased fat deposition in the bone marrow, impaired hematopoietic stem and progenitor cell (HSPC) function, and a propensity towards myeloid differentiation. This shift in lineage bias can lead to pre-malignant bone marrow conditions such as clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenias of undetermined significance (CCUS), frequently setting the stage for subsequent development of age-related cancers in myeloid or lymphoid lineages. Human aging has also been associated with diverse lipid alterations across tissues, such as decreased phospholipid membrane fluidity that arises as a result of increased saturated fatty acid (FA) accumulation and a decay in n-3 polyunsaturated fatty acid (PUFA) species by the age of 80 years, however the extent to which impaired FA metabolism contributes to hematopoietic aging is less clear. Here, comprehensive multi-omics analyses uncovered a role for a key PUFA biosynthesis gene, <i>ELOVL2</i>, in mouse and human immune cell aging. Whole transcriptome RNA-sequencing studies and complementary flow cytometric analyses of bone marrow from aged <i>Elovl2</i> mutant (enzyme-deficient) mice compared with age-matched controls revealed global downregulation in lymphoid cell markers and expression of genes involved specifically in B cell development. These studies unveiled CD79B, a vital molecular regulator of lymphoid progenitor development from the pro-B to pre-B cell stage, as a putative surface biomarker whose loss is associated with accelerated immune aging. The lipidome of mutant versus wild-type mice also displayed significant changes in the biophysical properties of cellular membranes. To investigate the relevance of these finding to human bone marrow aging, analyses of a single cell RNA-seq dataset of human HSPCs across the spectrum of human development and aging uncovered a rare subpopulation (&lt; 7%) of CD34⁺ HSPCs that expresses <i>ELOVL2</i> in healthy adult bone marrow. This HSPC subset, along with <i>CD79B</i>-expressing lymphoid-committed cells, were almost completely absent in CD34⁺ cells isolated from elderly bone marrow samples. Together, these findings uncover new roles for lipid metabolism enzymes in the molecular regulation of cellular aging and immune cell function in mouse and human hematopoiesis. In addition, because systemic loss of ELOVL2 enzymatic activity resulted in downregulation of B cell genes that are also associated with lymphoproliferative neoplasms, this study sheds light on an intriguing metabolic pathway that could be leveraged in future studies as a novel therapeutic modality to target blood cancers or other age-related conditions involving the B cell lineage.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"40 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832134","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}

{"title":"German longevity study reveals novel rare pro-longevity alleles clustering in mTOR signaling pathway","authors":"Daniel Kolbe, Janina Dose, Pasquale Putter, Malte Ziemann, Matthias Laudes, P. Eline Slagboom, Andre Franke, Joris Deelen, Almut Nebel","doi":"10.1007/s11357-025-01640-7","DOIUrl":"https://doi.org/10.1007/s11357-025-01640-7","url":null,"abstract":"<p>In this study, we investigated the contribution of rare coding variants to human longevity by analyzing whole exome sequencing data from 1245 German long-lived individuals (LLI) and 4105 geographically matched younger controls. We identified novel exome-wide significant associations at both the single-variant and gene level, with a significant over-representation of genes involved in mechanistic target of rapamycin (mTOR) signaling. As such, three rare single variants in the mTOR-pathway genes <i>RPS6</i>,<i> FLCN</i>, and <i>SIK3</i> were enriched in LLI. Additionally, <i>RWDD1</i> emerged as a strong candidate gene for longevity, with LLI exhibiting a statistically significant burden of rare missense variants in this gene. Other associations involved <i>PRAC2</i>, <i>SLC16 A6</i>, <i>FOCAD</i>, <i>IHH</i>, <i>MESD</i>, <i>HOXA4</i>, and <i>DNAJB13</i>. Furthermore, we observed an enrichment of protein-truncating variants in the genes <i>ASXL1</i> and <i>TET2</i> amongst LLI, likely as a result of clonal haematopoiesis. The study emphasizes the role of rare variants in human longevity, particularly through mTOR signaling.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"38 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832130","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}

{"title":"Reliability and validity of a full-body function Get-Up test in older adults","authors":"Nathan F. Meier, Brandon S. Klinedinst, Duck-chul Lee","doi":"10.1007/s11357-025-01643-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01643-4","url":null,"abstract":"<p>Identifying deficiencies in physical function in older adults is critical to evaluate important health outcomes like sarcopenia, but current protocols are expensive and require complex equipment. This study evaluates the reliability and validity of an inexpensive, simple new Get-Up test in older adults. It involves participants moving quickly from standing upright, to lying flat, then rising to a standing position unassisted. A total of 293 relatively healthy older adults without severe health conditions (e.g., cardiovascular, psychological, degenerative, or physical impairments) completed the Get-Up test twice for familiarization and twice for timed trials on two separate days alongside numerous validated clinical tests commonly used to assess strength, function, and fitness in older adults. ANOVA with post-hoc analysis and intraclass correlation (0.928 (95% CI [0.914, 0.940])) indicated strong reliability, with the second timed trial comparable to trials on a separate day. The Get-Up test was significantly (<i>p</i> &lt;.0001) negatively correlated with all referenced measures of strength (Biodex peak torque, <i>r</i> = −.41, 1-repetition maximum, <i>r</i> = −.26, handgrip, <i>r</i> = −.38) and function (Short Physical Performance Battery, <i>r</i> = −.49, gait speed, <i>r</i> = −.39) and significantly (<i>p</i> &lt;.0001) positively correlated with fitness (400-m walk, <i>r</i> =.70), which strongly predicted Get-Up test performance, suggesting good validity. Poor performance was associated with baseline sarcopenia prevalence (bottom tertile vs. top tertile: odds ratio 3.99 (95% CI 1.64–9.67)) and sarcopenia incidence after 1-year follow-up (hazard ratio 3.47 (1.10, 10.98)), suggesting potential to evaluate sarcopenia. This simple and safe Get-Up test requires minimal equipment, personnel, and expertise, yet it has good reliability and validity as a potential novel tool for full-body physical function in older adults that is associated with sarcopenia prevalence and incidence.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"21 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827697","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}

{"title":"HDAC11 deficiency regulates age-related muscle decline and sarcopenia","authors":"Renato Odria, Aina Cardús, Clara Gomis-Coloma, Marta Balanyà-Segura, Alexandra Mercado-Amarilla, Pau Maestre-Mora, Andrea Poveda-Sabuco, Joan Carles Domingo, Gisela Nogales-Gadea, Jose A. Gomez-Sanchez, Erica Hurtado, Mònica Suelves","doi":"10.1007/s11357-025-01611-y","DOIUrl":"https://doi.org/10.1007/s11357-025-01611-y","url":null,"abstract":"<p>Sarcopenia, defined as the progressive loss of skeletal muscle mass and function associated with ageing, has devastating effects in terms of reducing the quality of life of older people. Muscle ageing is characterised by muscle atrophy and decreased capacity for muscle repair, including a reduction in the muscle stem cell pool that impedes recovery after injury. Histone deacetylase 11 (HDAC11) is the newest member of the HDAC family and it is highly expressed in skeletal muscle. Our group recently showed that genetic deficiency in HDAC11 increases skeletal muscle regeneration, mitochondrial function and globally improves muscle performance in young mice. Here, we explore for the first time the functional consequences of HDAC11 deficiency in old mice, in homeostasis and during muscle regeneration. Aged mice lacking HDAC11 show attenuated muscle atrophy and postsynaptic fragmentation of the neuromuscular junction, but no significant differences in the number or diameter of myelinated axons of peripheral nerves. Maintenance of the muscle stem cell reservoir and advanced skeletal muscle regeneration after injury are also observed. HDAC11 depletion enhances mitochondrial fatty acid oxidation and attenuates age-associated alterations in skeletal muscle fatty acid composition, reducing drastically the omega-6/omega-3 fatty acid ratio and improving significantly the omega-3 index, providing an explanation for improved muscle strength and fatigue resistance and decreased mortality. Taken together, our results point to HDAC11 as a new target for the treatment of sarcopenia. Importantly, selective HDAC11 inhibitors have recently been developed that could offer a new therapeutic approach to slow the ageing process.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"30 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823167","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}

{"title":"Cerebral hypoperfusion, brain structural integrity, and cognitive impairment in older APOE4 carriers","authors":"Ioannis Pappas, Trevor Lohman, Shubir Dutt, Arunima Kapoor, Allison C. Engstrom, John Paul M. Alitin, Samuel Barnes, Ararat Chakhoyan, Lucas Saca, Raghav Gaggar, Elnaz Nourollahimoghadam, Danny J. J. Wang, Mark H. C. Lai, Elizabeth B. Joe, John M. Ringman, Hussein N. Yassine, Lon S. Schneider, Helena C. Chui, Arthur W. Toga, Berislav V. Zlokovic, Daniel A. Nation","doi":"10.1007/s11357-025-01642-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01642-5","url":null,"abstract":"<p>Cerebral blood flow (CBF) deficits, cognitive decline, and brain structural changes have been reported in older adults with and without apolipoprotein E-e4 (<i>APOE4</i>)-related risk for dementia. However, it remains unclear whether brain structural changes mediate the effects of hypoperfusion on cognitive impairment in <i>APOE4</i> carriers and non-carriers. We studied 166 (60–89 years) <i>APOE4</i> carriers (ε3/ε4 or ε4/ε4) and <i>APOE3</i> homozygotes (e3/e3) with and without cognitive impairment by clinical dementia rating (CDR) and neuropsychological testing. Pseudocontinuous arterial spin-labeling-MRI assessed regional CBF, and T1-anatomical and diffusion-MRI assessed structural integrity. Mediation analyses examined relationships among grey matter CBF, grey matter volume, and white matter integrity in regions underlying impairment in distinct cognitive ability domains. <i>APOE4</i> carriers with global/memory impairment (CDR 0.5) exhibited decreased CBF in the posterior cingulate, decreased grey matter volume in the hippocampus, parahippocampal gyrus, and posterior cingulate, and decreased white matter integrity in the cingulum relative to <i>APOE4</i> carriers with no impairment (CDR 0). Mediation analysis in <i>APOE4</i> carriers indicated decreased posterior cingulate CBF effects on global/memory impairment were mediated by decreased cingulum integrity. In the combined <i>APOE4</i> and <i>APOE3</i> carriers sample, there were direct effects of frontal and inferior parietal CBF and superior longitudinal fasciculus integrity on attention/executive impairment. There were also direct effects of left inferior frontal CBF on language impairment. Findings suggest links between hypoperfusion and brain structural integrity underlying global/memory impairment in <i>APOE4</i> carriers. Independent CBF relationships with structural integrity are also identified across genotypes and impairment domains.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"50 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823165","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}

{"title":"Bryostatin-1 improves function in arteries with suppressed endothelial cell autophagy","authors":"Jae Min Cho, Seul-Ki Park, Sohom Mookherjee, Emily Carolyn Peters, Paulo W. Pires, J. David Symons","doi":"10.1007/s11357-025-01650-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01650-5","url":null,"abstract":"<p>We have previously reported that when autophagy is suppressed in endothelial cells (ECs), a glycolytic defect limits shear-stress -induced ATP production to an extent that purinergic 2Y1 receptor (P2Y1R)-mediated activation of EC nitric oxide (NO) synthase (eNOS) is compromised. Subsequently we demonstrated the functional relevance of this finding in arteries from mice with genetic, pharmacological, and age-associated EC autophagy impairment. Using gain and loss of function approaches in vitro, we further revealed that p-PKCδ^T505 serves as a signaling link between P2Y1R activation and NO generation. Here we sought to discern the functional relevance of this observation. First, shear-stress- induced activating phosphorylation of eNOS (p-eNOS^S1177) that is otherwise prevented by knockdown of autophagy-related gene 3 (<i>Atg3</i>) in ECs was restored by the PKC agonist bryostatin-1. Next, in murine models of genetic and age-associated EC autophagy compromise, depressed vasodilation displayed by femoral and cerebral arteries was reversed by bryostatin-1 in a manner that could be prevented by concurrent NO synthase inhibition. Finally, the bryostatin-1-mediated normalization of intraluminal flow-induced vasodilation observed in femoral arteries from both models of EC autophagy disruption was mitigated by inhibiting downstream targets of p-PKCδ^T505 i.e., p-PKD^S744/S748 and p-PKD^S916. These findings provide evidence that stimulating PKC/PKD has strategic potential to restore compromised endothelial function in pathologies associated with suppressed EC autophagy e.g., aging.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"5 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823164","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}

{"title":"Exercise and survival benefit in cancer patients: evidence from a comprehensive meta-analysis","authors":"Zoltan Ungvari, Mónika Fekete, Péter Varga, Gyöngyi Munkácsy, János Tibor Fekete, Andrea Lehoczki, Annamaria Buda, Csaba Kiss, Anna Ungvari, Balázs Győrffy","doi":"10.1007/s11357-025-01647-0","DOIUrl":"https://doi.org/10.1007/s11357-025-01647-0","url":null,"abstract":"<p>Cancer remains a major global health challenge, and growing evidence suggests that physical activity is a key modifiable factor that may improve survival outcomes in cancer patients. However, a comprehensive, large-scale synthesis of the effects of post-diagnosis physical activity across multiple cancer types remains lacking. This meta-analysis aims to systematically evaluate the association between physical activity and survival in patients diagnosed with breast, lung, prostate, colorectal, and skin cancers. We conducted a comprehensive search in PubMed, Web of Science, Scopus, and Cochrane Library for studies on physical activity and cancer survival. Eligible studies (January 2000–November 2024) included adults (≥ 18 years) with breast, lung, prostate, colorectal, or skin cancer. Only prospective cohort and case–control studies reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall or cancer-specific mortality were included, with a minimum sample size of 100 and at least six months of follow-up. Meta-analysis was performed using metaanalysisonline.com, applying random-effects models and assessing heterogeneity via the I² statistic. Sensitivity analyses and publication bias (Egger’s test, funnel plots) were evaluated. The meta-analysis included 151 cohorts with almost 1.5 million cancer patients. Post-diagnosis physical activity was associated with significantly lower cancer-specific mortality across all five cancer types. The greatest benefit was observed in breast cancer, with a pooled hazard ratio (HR) of 0.69 (95% CI: 0.63–0.75), followed by prostate cancer (HR: 0.73, 95% CI: 0.62–0.87). Lung cancer patients who engaged in physical activity had a 24% lower risk of cancer-specific death (HR: 0.76, 95% CI: 0.69–0.84), while colorectal cancer patients experienced a similar benefit (HR: 0.71, 95% CI: 0.63–0.80). In skin cancer, physical activity was associated with a non-significant reduction in mortality (HR: 0.86, 95% CI: 0.71–1.05). These findings provide robust evidence supporting the survival benefits of post-diagnosis physical activity in cancer patients, particularly for breast, prostate, lung, and colorectal cancers. The results underscore the potential for incorporating structured physical activity interventions into oncological care to improve long-term patient outcomes.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"109 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823163","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}