The Journals of Gerontology Series A: Biological Sciences and Medical Sciences最新文献

{"title":"Frailty and the risk of age-related macular degeneration: a prospective cohort and Mendelian randomization study","authors":"Xinyu Zhu, Yikeng Huang, Li Liang, Xinyu Zhang, Zixuan Zhang, Yujin Jiang, Xiaoqian Wu, Chenxin Li, Zhi Zheng, Zhangli Bao, Wenjun Zou, Shuzhi Zhao","doi":"10.1093/gerona/glae300","DOIUrl":"https://doi.org/10.1093/gerona/glae300","url":null,"abstract":"Background Both frailty and age-related macular degeneration (AMD) are related to aging and may share some common mechanisms. We aimed to examine the observational and causal association between frailty and the risk of age-related macular degeneration (AMD). Methods We included 320,810 participants free of AMD at baseline from the UK Biobank. Frailty phenotypes were defined according to 5 components: weight loss, exhaustion, slow gait speed, low grip strength, and low physical activity. Cox proportional hazard models were used to evaluate the association between frailty phenotype and the risk of AMD. Causal relationship between frailty phenotype and AMD was examined using two-sample Mendelian randomization (MR) analysis. Results During a median follow-up of 12.81 years, 7,222 AMD cases were documented. After adjusting for confounding factors, compared with non-frail participants, both pre-frail and frail participants were significantly associated with an increased risk of AMD (HR 1.17, 95% CI: [1.11, 1.23] for pre-frailty and HR 1.55 [95% CI: 1.40, 1.73] for frailty). With each one-point increase in frailty phenotype score, the risk of AMD increased by 14%. Results from the two-sample MR analysis supported the potential causal effect of frailty phenotype on AMD. Conclusions Our findings suggested that frailty assessment may help identify at-risk populations and serve as a potential strategy for early prevention and management of AMD.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"280 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874264","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}

{"title":"Neuroprotective Effect of 1α,25-Dihydroxyvitamin D3 Against Cognitive impairment in D-galactose-induced Aging Mice","authors":"Ming Cai, Yiting Wang, Jingjing Lu, Yongchao Liang, Wenjie Yi, Fei Jiang","doi":"10.1093/gerona/glae298","DOIUrl":"https://doi.org/10.1093/gerona/glae298","url":null,"abstract":"Aging and age-related cognitive impairment have emerged as a growing global public health concern and remain no effective preventive strategies. Excessive oxidative stress and neuroinflammation have been proven to contribute to cognitive decline. Vitamin D maintains the redox balance and exerts immunomodulatory effects, but the specific role of vitamin D in aging and age-related cognitive impairment remains elusive. This study explored the neuroprotective effects and the potential molecular mechanisms of 1α,25-Dihydroxyvitamin D3 in the aging model. An aging model was established by the treatment of D-galactose for 14 weeks in Male KM mice. 0.1, 0.5, or 1 μg/kg 1α,25-Dihydroxyvitamin D3 were used in the intervention group for 8 weeks. Cognitive performance was evaluated using the Morris water maze test, and the levels of oxidative stress and neuroinflammation in the hippocampus were further analyzed. D-galactose induced memory impairment, whereas 1α,25-Dihydroxyvitamin D3 intervention prevented cognitive decline, accompanied by a reduction in neuronal apoptosis, an enhancement of synaptic plasticity, and a decrease in Aβ deposition. Meanwhile, 1α,25-Dihydroxyvitamin D3 dramatically attenuated oxidative stress, mitigated microglial cell activation, and ameliorated neuroinflammation by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (AREs) axis and inhibiting the NF-κB signaling pathway. This study provides evidence that 1α,25-Dihydroxyvitamin D3 might be a promising nutritional strategy for preventing cognitive decline in aging, thereby facilitating the clinical application and expanding the insight of vitamin D.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869962","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}

{"title":"An expert consensus statement on biomarkers of ageing for use in intervention studies","authors":"Giorgia Perri, Chloe French, César Agostinis-Sobrinho, Atul Anand, Radiana Dhewayani Antarianto, Yasumichi Arai, Joseph A Baur, Omar Cauli, Morgane Clivaz-Duc, Giuseppe Colloca, Constantinos Demetriades, Chiara de Lucia, Giorgio Di Gessa, Breno S Diniz, Catherine L Dotchin, Gillian Eaglestone, Bradley T Elliott, Mark A Espeland, Luigi Ferrucci, James Fisher, Dimitris K Grammatopoulos, Novi S Hardiany, Zaki Hassan-Smith, Waylon J Hastings, Swati Jain, Peter K Joshi, Theodora Katsila, Graham J Kemp, Omid A Khaiyat, Dudley W Lamming, Jose Lara Gallegos, Frank Madeo, Andrea B Maier, Carmen Martin-Ruiz, Ian J Martins, John C Mathers, Lewis R Mattin, Reshma A Merchant, Alexey Moskalev, Ognian Neytchev, Mary Ni Lochlainn, Claire M Owen, Stuart M Phillips, Jedd Pratt, Konstantinos Prokopidis, Nicholas J W Rattray, María Rúa-Alonso, Lutz Schomburg, David Scott, Sangeetha Shyam, Elina Sillanpää, Michelle M C Tan, Ruth Teh, Stephanie W Tobin, Carolina J Vila-Chã, Luigi Vorluni, Daniela Weber, Ailsa Welch, Daisy Wilson, Thomas Wilson, Tongbiao Zhao, Elena Philippou, Viktor I Korolchuk, Oliver M Shannon","doi":"10.1093/gerona/glae297","DOIUrl":"https://doi.org/10.1093/gerona/glae297","url":null,"abstract":"Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method. A three-round Delphi study was conducted using an online platform. In Round 1, expert panel members provided suggestions for candidate biomarkers of ageing. In Rounds 2 and 3, they voted on 500 initial statements (yes/no) relating to 20 biomarkers of ageing. Panel members could abstain from voting on biomarkers outside their expertise. Consensus was reached when there was ≥70% agreement on a statement/biomarker. Of the 460 international panel members invited to participate, 116 completed Round 1, 87 completed Round 2, and 60 completed Round 3. Across the 3 rounds, 14 biomarkers met consensus that spanned physiological (e.g., insulin-like growth factor 1, growth-differentiating factor-15), inflammatory (e.g., high sensitivity c-reactive protein, interleukin-6), functional (e.g., muscle mass, muscle strength, hand grip strength, Timed-Up-and-Go, gait speed, standing balance test, frailty index, cognitive health, blood pressure), and epigenetic (e.g., DNA methylation/epigenetic clocks) domains. Expert consensus identified 14 potential biomarkers of ageing which may be used as outcome measures in intervention studies. Future ageing research should identify which combination of these biomarkers has the greatest utility.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869939","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}

{"title":"Effects of a physical activity intervention on perceived stress, fatigue, and depressive symptoms in older adults: A secondary analysis of the LIFE Study","authors":"Emily J Smail, Christopher N Kaufmann, Abby C King, Mark A Espeland, Stephen Anton, Todd M Manini","doi":"10.1093/gerona/glae290","DOIUrl":"https://doi.org/10.1093/gerona/glae290","url":null,"abstract":"Background Engaging in physical activity is critical for maintaining well-being in older adults, particularly those at heightened risk for mobility disability. We assessed the effects of a physical activity (PA) intervention on perceived stress, fatigue, and depressive symptoms compared to a health education (HE) program in older adults with mobility challenges and evaluated differential effects of the interventions among those with the poorest self-rated mental health at baseline. Methods Secondary data analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study, a single-blinded, parallel randomized controlled trial conducted between February 2010 and December 2013. The PA intervention included walking, strength exercises, balance training, and flexibility activities. The HE intervention consisted of workshops on health topics for older adults. The main outcomes for our analysis included standardized scales with participants self-reporting their stress, fatigue, and depressive symptoms at baseline, 12 months, and 24 months post-randomization. Results Results from the 1,495 participants (Mage = 78 years; 66% female in both groups) showed no significant between-group differences in perceived stress, fatigue, or depressive symptom scores over time. However, in both intervention groups, participants with worse baseline scores showed a steady improvement in symptom scores over time compared to the remaining participants, who showed some decline (p-value for interaction<0.05). Conclusions Among mobility-impaired individuals, a long-duration, group-based PA intervention had no more impact on stress, fatigue, or depressive symptoms compared to a group-based HE intervention. However, participants with higher symptoms at baseline showed improvement over time in both intervention groups.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"263 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858459","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}

{"title":"Mexican Health and Aging Study Biomarker and Genetic Data Profile","authors":"Rafael Samper-Ternent, Jesús Daniel Zazueta-Borboa, Alejandra Michaels-Obregon, Dolly Reyes-Dumeyer, Sandra Barral, Giuseppe Tosto, Rebeca Wong","doi":"10.1093/gerona/glae270","DOIUrl":"https://doi.org/10.1093/gerona/glae270","url":null,"abstract":"The Mexican Health and Aging Study (MHAS) is one of the largest ongoing longitudinal studies of aging in Latin America, with six waves over 20 years. MHAS includes sociodemographic, economic, and health data from a nationally representative sample of adults 50 years and older in urban and rural Mexico. MHAS is designed to study the impact of diseases on adults’ health, function, and mortality. As Mexico is experiencing rapid population aging, providing adequate information to study this phenomenon is vital for designing and implementing public policies. The availability of biomarker and genetic data and longitudinal survey data elevates opportunities for research on aging in a low–middle-income country. This manuscript describes the profile of biomarkers and genetic data available in the MHAS study, including sample sizes and sociodemographic characteristics of participants who provided biospecimens for biomarker analyses, emphasizing recent genetic data. The sample size of individuals with anthropometric biomarkers was 2 707 (Wave 1—2001), 2 361 (Wave 2—2003), 2 086 (Wave 3—2012), and 2 051 (2016). Capillary blood samples were collected from 2 063 participants in 2012 (Wave 3) and 1 141 in 2016. Venous blood samples for blood-based biomarkers were collected from 2 003 participants in 2012 (Wave 3) and 752 in 2016. Venous blood samples were also collected for genetic data from 2 010 participants in 2012 (Wave 3) and 750 in 2016. A total of 7 821 participants provided saliva in 2018, and 2 671 provided hair in 2018. From these samples, a total of 7 204 have genome-wide genetic data, 8 600 have apolipoprotein-E genotype data, and 7 156 have genetic ancestry data.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841557","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}

{"title":"Longitudinal Decline of Exercise Capacity in Male and Female Mice","authors":"Megan L Pajski, Rosario Maroto, Chris Byrd, Ted G Graber","doi":"10.1093/gerona/glae293","DOIUrl":"https://doi.org/10.1093/gerona/glae293","url":null,"abstract":"The population of older adults is exponentially expanding. Alongside aging comes the onset of chronic disease, decline of functional capacity, and reduced quality of life. Thus, this population increase will stress the capacity and financial viability of health and long-term care systems. Developing pre-clinical models for age-related functional decline is imperative to advancing therapies that extend healthspan and prolong independence. Previously in a cross-sectional study, we established a powerful composite scoring system we termed CFAB (comprehensive functional assessment battery). CFAB measures physical function and exercise capacity using well-validated determinants to measure overall motor function, fore-limb strength, four-limb strength/endurance, aerobic capacity, and volitional exercise/activity rate. In the current work, we used CFAB to track cohorts of male and female C57BL/6 mice over the lifespan (measuring CFAB at 6, 12, 18, 24, and 28 months of age). Overall, we found statistically significantly declining function as the mice aged, with some differences between males and females in trajectory and slope. We also determined that body mass changes presented differently between sexes, and tracked body composition (fat percentage, using magnetic resonance imagery) in females. In a subset of mice, we tracked in vivo contractile physiology noting declines in plantar flexor maximum isometric torque. In summary, our data suggest that males and females declined at different rates. We confirmed the efficacy of CFAB to track longitudinal changes in exercise capacity and physical fitness in both males and females, further validating the system to track age-related functional decline.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849158","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}

{"title":"Objectively measured physical activity using wrist-worn accelerometers as a predictor of incident Alzheimer’s Disease in the UK Biobank","authors":"Angela Zhao, Erjia Cui, Andrew Leroux, Xinkai Zhou, John Muschelli, Martin A Lindquist, Ciprian M Crainiceanu","doi":"10.1093/gerona/glae287","DOIUrl":"https://doi.org/10.1093/gerona/glae287","url":null,"abstract":"Background Alzheimer’s disease (AD) affects over 6 million people and is the seventh-leading cause of death in the US. This study compares wrist-worn accelerometry-derived PA measures against traditional risk factors for incident AD in the UK Biobank. Methods Of 42,157 UK Biobank participants 65 years and older who had accelerometry data and no prior AD diagnosis, 157 developed AD by April 1, 2021 (264,988 person-years or on average 6.2 years of follow-up). 12 traditional predictors and 8 accelerometer-based PA measures were used in single- and multivariate Cox models. Their predictive performances for future AD diagnosis were compared across models using the repeated cross-validated concordance (rcvC). To account for potential reverse causality, sensitivity analyses were conducted by removing dropouts and cases within the first six months, one year, and two years. Results The best-performing individual predictors of incident AD were age (p < 0.0001, rcvC = 0.658) and moderate-to-vigorous PA (MVPA, p = 0.0001, rcvC = 0.622). Forward selection produced a model that included age, diabetes, and MVPA, rcvC = 0.681). Adding MVPA to the model containing age and diabetes improved its rcvC from 0.665 to 0.681 (p = 0.0030), more than all other potential risk factors considered. Conclusion Objective PA summaries are the best single predictors among modifiable risk factors with a predictive performance close to that of age. Adding PA summaries to traditional risk factors for AD substantially increases the predictive performance of these models. Increasing MVPA by 14.5 minutes/day reduces the hazard substantially, equivalent to two years younger.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805419","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}

{"title":"Does sleep moderate the effects of exercise training or complex mental and social activities on cognitive function in adults with chronic stroke? Secondary analysis of a randomized trial","authors":"Ryan S Falck, Ryan G Stein, Jennifer C Davis, Janice J Eng, Laura E Middleton, Peter A Hall, Teresa Liu-Ambrose","doi":"10.1093/gerona/glae264","DOIUrl":"https://doi.org/10.1093/gerona/glae264","url":null,"abstract":"Background Exercise (EX) or cognitive and social enrichment (ENRICH) are two strategies for promoting cognition post-stroke. Whether sleep moderates the effects of EX or ENRICH on cognition in adults with chronic stroke is unknown. Methods A three-arm parallel randomized clinical trial among community-dwelling adults aged 55+ years with chronic stroke (i.e., ≥12 months since stroke). Participants were randomized to 2x/week EX, ENRICH, or balance and tone control (BAT). At baseline, device-measured sleep duration and efficiency were measured using wrist-worn actigraphy; self-reported quality was measured by Pittsburgh Sleep Quality Index (PSQI). Participants were categorized at baseline as having good or poor device-measured duration, device-measured efficiency, or self-reported quality based on PSQI. The primary cognitive outcome was Alzheimer’s Disease Assessment Scale Plus (ADAS-Cog-Plus) measured at baseline, 6 months (end of intervention), and 12 months (6-month follow-up). We examined if baseline sleep categorizations (i.e., good/poor) moderated effects of EX or ENRICH on ADAS-Cog-Plus. Results We enrolled 120 participants in the trial (EX=34; ENRICH=34; BAT=52). Sleep quality (i.e., device-measured sleep efficiency or self-reported sleep quality) categorization moderated effects of EX (but not ENRICH) on ADAS-Cog-Plus. Compared with BAT participants with poor sleep quality, EX participants with poor sleep quality had better ADAS-Cog-Plus performance at 6 months (estimated mean difference for those with poor device-measured sleep efficiency: -0.48; 95% CI:[-0.85, -0.10]; p=0.010); estimated mean difference for those with poor self-reported sleep quality: -0.38; 95% CI:[-0.70, -0.07]; p=0.014). There was no effect of EX on ADAS-Cog-Plus for participants with good sleep quality. Device-measured sleep duration did not moderate intervention effects. Conclusion Exercise is particularly beneficial in improving cognitive function in adults with chronic stroke and poor sleep quality.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597139","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}

{"title":"Longitudinal Changes in Peak Expiratory Flow Predict Risk for Incident Dementia","authors":"Patrick T Donahue, Aparna Balasubramanian, Qian-Li Xue, Jennifer A Schrack, Michelle C Carlson","doi":"10.1093/gerona/glae249","DOIUrl":"https://doi.org/10.1093/gerona/glae249","url":null,"abstract":"Background Impaired respiratory function, measured via peak expiratory flow (PEF), has been associated with increased dementia risk. However, much of the current literature uses cross-sectional measures of PEF, whereas longitudinal relationships between changes in respiratory function and dementia risk are underexplored. Methods Using 10 years of data (2011-2021) from 2,439 adults ages 65 and older in the National Health and Aging Trends Study (NHATS), we examined whether 5-year changes in PEF (2011-2016) were associated with risk for incident dementia over the subsequent 5-year period (2017-2021). PEF slopes for each participant were estimated using linear mixed-effects models and then grouped into quartiles: rapid, moderate, mild, and no declines. Discrete-time Cox proportional hazards models were used to estimate the risk for incident dementia by PEF slope category, while controlling for several health and sociodemographic characteristics. Results After excluding dementia cases during the exposure window (2011-2016), we identified 338 cases of incident dementia (13.9%) between 2017-2021. Rapid PEF declines between 2011-2016 were associated with 85% higher risk for incident dementia between 2017-2021 compared to those with no declines in PEF (HR=1.85; 95% CI [1.24, 2.76]). Results were robust to several sensitivity analyses. Conclusions These findings demonstrate that declines in PEF may precede declines in cognition, suggesting that respiratory function may be an important dementia risk factor in older adults. Additionally, these findings highlight the utility of measuring PEF via a peak flow meter, which is a simple and inexpensive measure of respiratory function.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489752","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}

{"title":"Late-onset caloric restriction improves cognitive performance and restores circadian patterns of neurotrophic, clock and epigenetic factors in the hippocampus of male old rats","authors":"Fernando Gabriel Altamirano, Ivanna Castro-Pascual, Ivana Tamara Ponce, Cinthia Daiana Coria-Lucero, Ethelina Cargnelutti, Mariana Lucila Ferramola, Marcela Silvia Delgado, Ana Cecilia Anzulovich, María Gabriela Lacoste","doi":"10.1093/gerona/glae252","DOIUrl":"https://doi.org/10.1093/gerona/glae252","url":null,"abstract":"Aging is a complex multifactorial process that results in a general functional decline, including cognitive impairment. Caloric restriction (CR) can positively influence the aging processes and delay cognitive decline. There is a rhythmic variation in memory and learning processes throughout the day, indicating the involvement of the circadian clock in the regulation of these processes. Despite growing evidence on the efficacy of CR, it has not yet been fully determined whether starting this strategy at an advanced age is beneficial for improving quality of life and eventually, for protection against age-related diseases. Here, we investigated the effect of late-onset CR on the temporal organization of the molecular clock machinery, molecules related to cognitive processes and epigenetic regulation, in the hippocampus of male old rats maintained under constant darkness conditions. Our results evidenced the existence of a highly coordinated temporal organization of Bmal1, Clock, Bdnf, Trkb, Dnmts, Sirt1, and Pgc-1α in the hippocampus of young adult rats. We observed that aging led to cognitive deficits and loss of circadian oscillations of all the above variables. Interestingly, CR restored circadian rhythmicity in all cases and, in addition, improved the cognitive performance of the old animals. This work would highlight the importance of the circadian clock and its synchronization with feeding signals, as the basis of the beneficial effects of CR. Thus, lifestyle modifications, such as CR, might be a powerful intervention to preserve hippocampal circadian organization and cognitive health during aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489749","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}