Genesio M Karere, Fang-Chi Hsu, Russell T Hepple, Paul M Coen, Steve Cummings, Anne Newman, Nancy W Glynn, Lauren Sparks, Nancy E Lane, Jianzhao Xu, Nathan Wagner, Ge Li, Jeanne Chan, Laura A Cox, Stephen Kritchevsky
{"title":"MicroRNA signatures of VO2peak in older adult participants of the Study of Muscle, Mobility and Aging.","authors":"Genesio M Karere, Fang-Chi Hsu, Russell T Hepple, Paul M Coen, Steve Cummings, Anne Newman, Nancy W Glynn, Lauren Sparks, Nancy E Lane, Jianzhao Xu, Nathan Wagner, Ge Li, Jeanne Chan, Laura A Cox, Stephen Kritchevsky","doi":"10.1093/gerona/glaf159","DOIUrl":"10.1093/gerona/glaf159","url":null,"abstract":"<p><strong>Background: </strong>Peak oxygen consumption during exercise (VO2peak), is a direct measure of cardiorespiratory fitness (CF), a key indicator of physical function and overall health. However, the molecular changes that underpin VO2peak variation are not clear. Our objective is to understand the miRNA signatures that relate to VO2peak variation, which could provide insights to novel mechanisms that contribute to low VO2peak.</p><p><strong>Methods: </strong>We used small RNA sequencing to analyze baseline, cross-sectional serum samples from 72 participants (70-91 yrs old). We analyzed samples from individuals with low or high VO2peak (N = 18/group) as well as samples from 36 randomly selected participants spanning the entire spectrum of VO2peak. We used LIMMA analysis package for regression analysis and to identify differentially expressed miRNAs.</p><p><strong>Results: </strong>We identified 1,055 miRNAs expressed in all serum samples. Expression of 65 miRNAs differed between participants with low and high VO2peak (p < 0.05). After p-value adjustment, expression of 5 miRNAs (miR-1301-3p, -431-5p, -501-5p, -519a-3p, and -18a-3p) remained significantly different (FDR = 0.05). The Area Under the Curve for the five miRNAs ranged from 0.77 to 0.84. The optimal sensitivity and specificity ranged from 70 to 80% and 80 to 90%, respectively. After adjustment for age and sex covariates, 46 miRNAs significantly correlated with VO2peak (p < 0.05) and miR-519a-3p remained significant based on adjusted p-values.</p><p><strong>Conclusions: </strong>We identified a miRNA signature of VO2peak in older individuals that might provide insights to novel mechanisms that drive low VO2peak. Future studies will validate the findings in a larger, longitudinal study cohort.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel D Callow, Yiwei Yue, Idiatou Diallo, Jill A Rabinowitz, Yang An, Alfonso J Alfini, Mark N Wu, Sarah K Wanigatunga, Amal A Wanigatunga, Luigi Ferrucci, Eleanor M Simonsick, Jennifer A Schrack, Adam P Spira
{"title":"Associations of Accelerometer-Estimated Sleep with Cardiorespiratory Fitness and Energetic Efficiency among Middle-Aged and Older Adults.","authors":"Daniel D Callow, Yiwei Yue, Idiatou Diallo, Jill A Rabinowitz, Yang An, Alfonso J Alfini, Mark N Wu, Sarah K Wanigatunga, Amal A Wanigatunga, Luigi Ferrucci, Eleanor M Simonsick, Jennifer A Schrack, Adam P Spira","doi":"10.1093/gerona/glaf130","DOIUrl":"https://doi.org/10.1093/gerona/glaf130","url":null,"abstract":"<p><strong>Background: </strong>Sleep disturbances and cardiovascular disease are common and often co-occur in middle-aged and older adults, but less is known about associations of sleep with cardiorespiratory fitness and energy efficiency in these populations. We examined cross-sectional associations of accelerometer-derived sleep metrics with cardiorespiratory fitness, walking energetics, and resting metabolic rate, and explored whether associations were moderated by age, sex, and race.</p><p><strong>Methods: </strong>We studied 263 participants from the Baltimore Longitudinal Study of Aging (mean age 72.7 ± 10.1 years, 53.6% women). Predictors included total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), wake after sleep onset (WASO), and average wake bout length (WBL). Outcomes included measures of cardiorespiratory fitness (ie, maximal oxygen consumption (VO2peak)) and energetic efficiency (ie, energetic cost of walking (ECW) and resting metabolic rate (RMR)).</p><p><strong>Results: </strong>After adjusting for demographics, comorbidities, and self-reported physical activity, longer WBL was associated with lower VO2peak (B=-1.01 ml/kg/min, p < 0.01) and higher RMR (B = 43.25 kcal, p < 0.05), lower SE was associated with lower VO2peak (B = 1.07 ml/kg/min, p < 0.01), and shorter TST was associated with lower VO2peak (B = 0.33 ml/kg/min, p < 0.05). Higher SE was associated with lower RMR among middle-aged adults but not older adults (interaction p-value < 0.05).</p><p><strong>Conclusion: </strong>Shorter TST, longer WBL, and lower SE are associated with poorer cardiorespiratory fitness and energetic efficiency among middle-aged and older adults. Longitudinal studies are needed to understand the temporality of these associaitons and potential targets for interventions in these populations.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catherine G Derington, Ransmond O Berchie, Daniel O Scharfstein, Ryan M Andrews, Tom H Greene, Yizhe Xu, Jordan B King, Mark A Supiano, Joshua A Sonnen, Jeff Williamson, Nicholas M Pajewski, Jeremy J Pruzin, Jordana B Cohen, Adam P Bress
{"title":"Effect of Initiation and Continuous Adherence to ARBs Versus ACEIs on Risk of Adjudicated Mild Cognitive Impairment or Dementia.","authors":"Catherine G Derington, Ransmond O Berchie, Daniel O Scharfstein, Ryan M Andrews, Tom H Greene, Yizhe Xu, Jordan B King, Mark A Supiano, Joshua A Sonnen, Jeff Williamson, Nicholas M Pajewski, Jeremy J Pruzin, Jordana B Cohen, Adam P Bress","doi":"10.1093/gerona/glaf028","DOIUrl":"10.1093/gerona/glaf028","url":null,"abstract":"<p><strong>Background: </strong>Whether the differing mechanistic effects between angiotensin-2 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) on the renin-angiotensin system translate to differential effects on clinical cognitive outcomes is unclear.</p><p><strong>Methods: </strong>We employed an active comparator, new-user cohort study to emulate a target trial evaluating the per-protocol effect of initiating and continuously adhering to an ARB versus ACEI on adjudicated amnestic mild cognitive impairment (MCI) and probable dementia (PD) in the Systolic Blood Pressure Intervention Trial (SPRINT). Inverse probability of treatment and censoring weighted cumulative incidence functions accounted for confounding, the competing risk of death, adherence, and loss to follow-up.</p><p><strong>Results: </strong>Of 9,361 SPRINT participants (mean age 67.1 ± 9.5 years, 36.7% female, 58.7% non-Hispanic White), 710 and 1,289 were new users of an ARB or ACEI. Overall, 291 (41.0%) ARB initiators and 854 (66.3%) ACEI initiators were nonadherent during follow-up. The IP-weighted 4-year probabilities of full adherence and being alive among ARB was 56.0% (95% CI: 52.2%-59.9%) and 30.5% (95% CI: 28.0%-33.1%) for ACEI. The 4-year weighted risk ratios (RR) for amnestic MCI/PD and for amnestic MCI/PD/death with initiation and full adherence to ARB versus ACEI were 0.94 (95% CI: 0.66-1.29) and 0.79 (95% CI: 0.58-1.06). The weighted 4-year weighted RR for all-cause death with ARB versus ACEI initiation and adherence was 0.36 (95% CI: 0.14-0.76).</p><p><strong>Conclusions: </strong>In this target trial emulation of older adults at high risk for cardiovascular disease, there was insufficient evidence to conclude a beneficial effect of initiating and continuously adhering to an ARB versus ACEI on adjudicated clinical cognitive outcomes.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariateresa Mazzetto, Kathrin Reichwald, Philipp Koch, Marco Groth, Alessandro Cellerino
{"title":"Analysis of Different Strains of the Turquoise Killifish Identify Transcriptomic Signatures Associated With Heritable Lifespan Differences.","authors":"Mariateresa Mazzetto, Kathrin Reichwald, Philipp Koch, Marco Groth, Alessandro Cellerino","doi":"10.1093/gerona/glae255","DOIUrl":"10.1093/gerona/glae255","url":null,"abstract":"<p><p>The African turquoise killifish Nothobranchius furzeri represents an emerging short-lived vertebrate model for aging research. Captive strains of this species are characterized by large differences in lifespan. To identify gene expression correlates of this lifespan differences, we analyzed a public transcriptomic dataset comprising 4 different tissues in addition to embryos. We focused on the GRZ and the MZM0410 captive strains, which show a near twofold difference in lifespan, but similar growth- and maturation-rates and validated the results in a newly generated dataset from a third longer-lived strain. The 2 strains show distinct transcriptome expression patterns already as embryos and the genotype has a larger effect than age on gene expression, both in terms of number of differentially expressed genes and magnitude of regulation. Network analysis detected RNA processing and histone modifications as the most prominent categories upregulated in GRZ. This strain also showed idiosyncratic expression patterns, such as high expression of DND is somatic tissues and transcriptional aging signatures already at sexual maturity (anticipated aging) in all 4 tissues, suggesting that short lifespan is the results of events that occur early in life rather than the progressive accumulation of strain-dependent differences. The GRZ strain is the most commonly used N furzeri strain in intervention studies and our results warrant replication of at least key findings in longer-lived strains.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huan Zhou, Yong Li, Di Miao, Jiayu Zhang, Lisa Yang, An Li, Ruoyan Cao
{"title":"Associations of Periodontitis With Biological Aging Among U.S. Adults: An Exploratory Mediation Analysis via Lactate.","authors":"Huan Zhou, Yong Li, Di Miao, Jiayu Zhang, Lisa Yang, An Li, Ruoyan Cao","doi":"10.1093/gerona/glaf061","DOIUrl":"10.1093/gerona/glaf061","url":null,"abstract":"<p><strong>Background: </strong>To investigate the potential role of lactate in the relationship between periodontitis and biological aging.</p><p><strong>Methods: </strong>Cross-sectional data from 9 652 participants in the National Health and Nutrition Examination Survey 2009-2014 were analyzed. Periodontitis was categorized based on the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC/AAP) classification. Biological aging was assessed based on KDM-BA acceleration and PhenoAge acceleration, while lactate levels were assessed using lactate dehydrogenase (LDH). Weighted multivariable linear regression analyses were conducted to examine the association between periodontitis and biological aging. Additionally, exploratory mediation analyses were carried out to determine the mediating effect of LDH on this association.</p><p><strong>Results: </strong>Participants with moderate/severe periodontitis showed accelerated biological aging and higher serum LDH levels. Similarly, mean attachment loss (AL) and probing pocket depth (PPD) were positively associated with biological aging and serum LDH levels. Furthermore, serum LDH was found to mediate 8.4% and 3.8% of the associations between periodontitis and KDM-BA acceleration and PhenoAge acceleration, respectively. LDH also explained 11.0% and 4.4% of the association between mean PPD and KDM-BA acceleration and PhenoAge acceleration, respectively. However, the role of LDH in the relationship between mean AL and biological aging was not observed.</p><p><strong>Conclusions: </strong>These findings indicate that LDH, an enzyme that converts pyruvate to lactate, mediates the association between periodontitis and biological aging. However, additional longitudinal or interventional studies are needed to more effectively assess causality and confirm our findings.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura McDaniel, Ime Essien, Samuel Lefcourt, Ephrata Zelleke, Arushi Sinha, Rama Chellappa, Peter M Abadir
{"title":"Aging With Artificial Intelligence: How Technology Enhances Older Adults' Health and Independence.","authors":"Laura McDaniel, Ime Essien, Samuel Lefcourt, Ephrata Zelleke, Arushi Sinha, Rama Chellappa, Peter M Abadir","doi":"10.1093/gerona/glaf086","DOIUrl":"10.1093/gerona/glaf086","url":null,"abstract":"<p><strong>Background: </strong>As the global population ages healthcare challenges are escalating. Frailty, a clinical syndrome characterized by decreased reserve and resilience to stressors, is critically linked to adverse health outcomes in older adults. However, artificial intelligence (AI)-driven technologies offer promising solutions for revolutionizing older individuals care and enhancing senior health and independence.</p><p><strong>Objective: </strong>This paper explores how AI-driven technologies, including wearables, nonwearable devices, and wireless systems, are transforming senior care. These innovations enable continuous health monitoring, fall detection, medication adherence, and cognitive assistance.</p><p><strong>Recent findings: </strong>Recent advancements in sensor technology, machine learning/AI algorithms, and user interface design have made these technologies more effective and accessible to older adults. Key benefits include early health issue detection, improved medication adherence, reduced hospitalizations, extended independent living, and improved quality of life. Privacy concerns, ease of use, and technology adoption are challenges that must be addressed.</p><p><strong>Conclusion: </strong>Thoughtfully designed AI wearables and supportive policies and infrastructure can significantly enhance seniors' quality of life while reducing caregiver burden and healthcare costs. As technology advances, AI-driven solutions across wearable, nonwearable, and wireless devices are set to become indispensable in global strategies for healthy aging.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":"80 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rapamycin Alters the Feeding Preference for Amino Acids and Sugar in Female Drosophila.","authors":"Guixiang Yu, Qihao Yang, Qi Wu","doi":"10.1093/gerona/glaf093","DOIUrl":"10.1093/gerona/glaf093","url":null,"abstract":"<p><p>Rapamycin has demonstrated significant lifespan-extending effects across a variety of model organisms, positioning it as one of the most promising antiaging agents currently under investigation. Nonetheless, chronic administration of rapamycin may induce diverse adverse reactions, primarily due to its influence on energy metabolism. Here, using Drosophila melanogaster as a model, we show that rapamycin significantly alters feeding behaviors in a dose-dependent manner. Specifically, both long-term and short-term administration of the optimal life-extending dose of rapamycin decreases the protein preference while increasing sugar intake in female flies. Utilizing a chemically defined diet, we identified that these alterations in amino acid and sugar feeding preferences occur as early as the second day of rapamycin exposure, preceding any detectable decline in fecundity. Furthermore, rapamycin also modifies amino acid preference even in taste-blind females, indicating that postingestive nutritional learning mechanisms, independent of food taste value, are sufficient to mediate the effects of rapamycin on feeding behavior. However, such changes in macronutrient preferences were absent in males and sterile mutant females. Collectively, our study suggests that the modification of feeding behavior could be a non-negligible side effect of rapamycin treatment, and this effect is influenced by both sex and reproductive status.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyle J Bourassa, Livia Anderson, Sandra Woolson, Paul A Dennis, Melanie E Garrett, Lauren Hair, Michelle Dennis, Karen Sugden, Benjamin Williams, Renate Houts, Patrick S Calhoun, Jennifer C Naylor, Allison E Ashley-Koch, Jean C Beckham, Avshalom Caspi, Gregory A Taylor, Katherine S Hall, Terrie E Moffitt, Nathan A Kimbrel
{"title":"Accelerated Epigenetic Aging and Prospective Morbidity and Mortality Among U.S. Veterans.","authors":"Kyle J Bourassa, Livia Anderson, Sandra Woolson, Paul A Dennis, Melanie E Garrett, Lauren Hair, Michelle Dennis, Karen Sugden, Benjamin Williams, Renate Houts, Patrick S Calhoun, Jennifer C Naylor, Allison E Ashley-Koch, Jean C Beckham, Avshalom Caspi, Gregory A Taylor, Katherine S Hall, Terrie E Moffitt, Nathan A Kimbrel","doi":"10.1093/gerona/glaf088","DOIUrl":"10.1093/gerona/glaf088","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic aging measures have promise as surrogate health outcomes in randomized control trials and observational cohort studies. The value of these measures, however, will reflect the extent to which they are associated with prospective health outcomes in real-world medical settings.</p><p><strong>Methods: </strong>Using data from 2 216 post-9/11 veterans from the VISN 6 MIRECC's Post-Deployment Mental Health Study, we examined whether accelerated epigenetic aging, assessed by DunedinPACE, was associated with prospective chronic disease morbidity, predicted healthcare costs, and mortality over an average of 13.1 years of electronic health record follow-up.</p><p><strong>Results: </strong>Veterans with faster DunedinPACE aging scores developed more chronic disease over the subsequent 5 years (RR, 1.25; 95% CI, 1.14-1.36), 10 years (RR, 1.31; 95% CI, 1.21-1.40), and 15 years (RR, 1.36; 95% CI, 1.22-1.52). Faster aging scores were also associated with increases in predicted healthcare costs over the next 5 years (β = 0.08; 95% CI, 0.03-0.13), 10 years (β = 0.23, 95% CI, 0.15-0.31), and 15 years (β = 0.21; 95% CI, 0.11-0.30). Faster DunedinPACE aging scores were associated with greater risk for incident myocardial infarction (84%), stroke (38%), diabetes (56%), cancer (25%), liver disease (44%), and renal disease (34%), as well as greater risk of mortality due to all-causes (38%) and chronic disease (74%). These results remained when adjusting for demographic, biomarker, and smoking covariates.</p><p><strong>Conclusions: </strong>Our findings suggest DunedinPACE is a biomarker of accelerated aging that is prospectively associated with chronic disease morbidity and mortality, as assessed using health records from an integrated healthcare system.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human Peripheral Blood Leukocyte Transcriptome-Based Aging Clock Reveals Acceleration of Aging by Bacterial or Viral Infections.","authors":"Xin Gao, Si-Jia Li, Jian-Ping Cai","doi":"10.1093/gerona/glaf054","DOIUrl":"10.1093/gerona/glaf054","url":null,"abstract":"<p><p>The aging of the population is a global concern. In the post-coronavirus disease 2019 (COVID-19) pandemic era, there are no effective methods to identify aging acceleration due to infection. In this study, we conducted whole-transcriptome sequencing on peripheral blood samples from 35 healthy individuals (22-88 years old). By analyzing the changes in mRNA, lncRNA, and miRNA expression, we investigated the characteristics of transcriptome alterations during the aging process. ceRNA networks were constructed, and 10 genes (CD248, PHGDH, SFXN2, MXRA8, NOG, TTC24, PHYKPL, CACHD1, BPGM, and TWF1) were identified as potential aging markers and used to construct an aging clock. Moreover, our aging clock categorized individuals into slow-, average-, and quick-aging groups, highlighting a link between accelerated aging and infection-related clinical parameters. Pseudotime analysis further revealed 2 distinct aging trajectories, corroborating the variations in the aging rate identified by the aging clock. Furthermore, we validated the results using the OEP001041 data set (277 healthy individuals aged 17-75), and data sets comprising patients with infectious diseases (n = 1 558). Our study revealed that infection accelerates aging via increased inflammation and oxidative stress in infectious disease patients. Besides, the aging clock exhibited alterations after infection, highlighting its potential for assessing the aging rate after patient recovery. In conclusion, our study introduces a novel aging clock to assess the aging rate in healthy individuals and those with infections, revealing a strong link between accelerated aging and infections through inflammation and oxidative stress. These findings offer valuable insights into aging mechanisms and potential strategies for healthy aging.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johanna Drewelies, Jan Homann, Valentin Max Vetter, Sandra Düzel, Simone Kühn, Laura Deecke, Elisabeth Steinhagen-Thiessen, Philippe Jawinski, Sebastian Markett, Ulman Lindenberger, Christina M Lill, Lars Bertram, Ilja Demuth, Denis Gerstorf
{"title":"There Are Multiple Clocks That Time Us: Cross-Sectional and Longitudinal Associations Among 14 Alternative Indicators of Age and Aging.","authors":"Johanna Drewelies, Jan Homann, Valentin Max Vetter, Sandra Düzel, Simone Kühn, Laura Deecke, Elisabeth Steinhagen-Thiessen, Philippe Jawinski, Sebastian Markett, Ulman Lindenberger, Christina M Lill, Lars Bertram, Ilja Demuth, Denis Gerstorf","doi":"10.1093/gerona/glae244","DOIUrl":"10.1093/gerona/glae244","url":null,"abstract":"<p><p>Aging is a complex process influenced by mechanisms operating at numerous levels of functioning. Multiple biomarkers of age have been identified, yet we know little about how the different alternative age indicators are intertwined. In the Berlin Aging Study II (nmin = 328; nmax = 1 517, women = 51%; 14.27 years of education), we examined how levels and 7-year changes in indicators derived from blood assays, magnetic resonance imaging brain scans, other-ratings, and self-reports converge among older adults. We included 8 epigenetic biomarkers (incl. 5 epigenetic \"clocks\"), a BioAge composite from clinical laboratory parameters, brain age, skin age, subjective age, subjective life expectancy, and subjective health horizon. We found moderate associations within aging domains, both cross-sectionally and longitudinally over 7 years. However, associations across different domains were infrequent and modest. Notably, participants with older BioAge had correspondingly older epigenetic ages. Our results suggest that different aging clocks are only loosely interconnected and that more specific measures are needed to differentiate healthy from unhealthy aging.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}