Frontiers in aging最新文献

{"title":"Endurance exercise preserves physical function in adult and older male C57BL/6 mice: high intensity interval training (HIIT) <i>versus</i> voluntary wheel running (VWR).","authors":"Megan L Pajski, Chris Byrd, Nainika Nandigama, Emily Seguin, Anna Seguin, Alyssa Fennell, Ted G Graber","doi":"10.3389/fragi.2024.1356954","DOIUrl":"10.3389/fragi.2024.1356954","url":null,"abstract":"<p><p>Exercise has been shown to improve physical function, mitigate aspects of chronic disease and to potentially alter the trajectory of age-related onset of frailty and sarcopenia. Reliable and valid preclinical models are necessary to elucidate the underlying mechanisms at the intersection of age, exercise, and functional decline. The purpose of this study was to compare, head to head, the effects of two common pre-clinical models of endurance exercise: high intensity interval training (HIIT) and voluntary wheel running (VWR). The hypothesis was that a prescribed and regimented exercise program, HIIT, would prove to be a superior training method to unregulated voluntary exercise, VWR. To investigate this hypothesis, we evaluated adult (n = 24, designated 10 m, aged 6 months at the beginning of the study, 10 months at its completion) and older adult (n = 18, designated 26 m, aging from 22 months to 26 months over the course of the study) C57BL/6 male mice. These mice were randomly assigned (with selection criteria) to a 13-week program of voluntary wheel running (VWR), high intensity interval training (HIIT), or sedentary control (SED). The functional aptitude of each mouse was determined pre- and post-training using our composite CFAB (comprehensive functional assessment battery) scoring system consisting of voluntary wheel running (volitional exercise and activity rate), treadmill (endurance), rotarod (overall motor function), grip meter (forelimb strength), and inverted cling (whole body strength/endurance). To measure sarcopenia, we tracked body mass, body composition (with EchoMRI), plantar flexor torque (in 10 m), and measured muscle wet mass post-training. Overall, adult CFAB scores decreased while body mass and percent body fat increased as they matured; however, exercise significantly mitigated the changes (<i>p</i> < 0.05) compared to SED. Older adults demonstrated preservation of function (CFAB) and reduced body fat (<i>p</i> < 0.05) compared to SED. To conclude, both types of exercise maintained physical function equally in older mice.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1356954"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10958787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208308","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":"Assessing muscular power in older adults: evaluating the predictive capacity of the 30-second chair rise test.","authors":"Niladri Kumar Mahato, Alexandria Davis, Janet E Simon, Brian C Clark","doi":"10.3389/fragi.2024.1302574","DOIUrl":"10.3389/fragi.2024.1302574","url":null,"abstract":"<p><p><b>Background:</b> Timed chair rise tests are frequently used as a substitute for assessing leg muscle strength or power. To determine if timed chair rise tests are an indicator of lower extremity muscle power, we examined the relationship between the repetitions completed in a 30-s chair rise test and the power generated during the test. <b>Methods:</b> Seventy-five individuals participated in this study (n = 30 < 65 years and 45 ≥ 65 years). Participants underwent a 30-s chair rise test while instrumented with a power analyzer. Handgrip strength was also evaluated. <b>Results:</b> The relationship between chair rise repetitions and <i>average</i> chair rise power was <i>R</i> ² = 0.32 (<i>p</i> < 0.001). Chair rise repetitions when regressed on a <i>total</i> (i.e., summed) chair rise power, it yielded <i>R</i> ² = 0.70 with data from all participants combined (<i>p</i> < 0.001). A mediation analysis indicated that anthropometrics partially mediates the relationship between chair rise repetitions and total chair rise power accounting for 2.8%-6.9% of the variance. <b>Conclusion:</b> Our findings indicate that in older adults, the overall performance of chair rises offers limited information about the average power per rise but is more indicative of the cumulative power exerted. Thus, the total number of chair rises in a 30-s test is likely a more comprehensive metric of overall muscular power, reflecting endurance aspects as well. Additionally, we found that personal physical attributes, such as height and weight, partially influence the link between chair rise count and total power, highlighting the importance of factoring in individual body metrics in assessments of muscular performance.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1302574"},"PeriodicalIF":3.3,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177999","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":"Editorial: Women in aging and the immune system.","authors":"Jenna M Bartley, Anshu Agrawal","doi":"10.3389/fragi.2024.1386626","DOIUrl":"https://doi.org/10.3389/fragi.2024.1386626","url":null,"abstract":"","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1386626"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10948595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178001","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":"Editorial: Effects of vascular function and aging on brain circulation and neurodegeneration.","authors":"Benjamin Petersen, Sharon Negri, Madison Milan, Helen Shi, Zeke Reyff, Cade Ballard, Jennifer Ihuoma, Andrea Di Francesco, Stefano Tarantini","doi":"10.3389/fragi.2024.1385066","DOIUrl":"https://doi.org/10.3389/fragi.2024.1385066","url":null,"abstract":"","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1385066"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10948611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178000","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":"Alterations in metabolic pathways: a bridge between aging and weaker innate immune response.","authors":"Zahra Saleh, Sara Mirzazadeh, Fatemeh Mirzaei, Kamran Heidarnejad, Seppo Meri, Kurosh Kalantar","doi":"10.3389/fragi.2024.1358330","DOIUrl":"https://doi.org/10.3389/fragi.2024.1358330","url":null,"abstract":"<p><p>Aging is a time-dependent progressive physiological process, which results in impaired immune system function. Age-related changes in immune function increase the susceptibility to many diseases such as infections, autoimmune diseases, and cancer. Different metabolic pathways including glycolysis, tricarboxylic acid cycle, amino acid metabolism, pentose phosphate pathway, fatty acid oxidation and fatty acid synthesis regulate the development, differentiation, and response of adaptive and innate immune cells. During aging all these pathways change in the immune cells. In addition to the changes in metabolic pathways, the function and structure of mitochondria also have changed in the immune cells. Thereby, we will review changes in the metabolism of different innate immune cells during the aging process.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1358330"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177998","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":"Disrupting the SKN-1 homeostat: mechanistic insights and phenotypic outcomes.","authors":"Chris D Turner, Carmen M Ramos, Sean P Curran","doi":"10.3389/fragi.2024.1369740","DOIUrl":"10.3389/fragi.2024.1369740","url":null,"abstract":"<p><p>The mechanisms that govern maintenance of cellular homeostasis are crucial to the lifespan and healthspan of all living systems. As an organism ages, there is a gradual decline in cellular homeostasis that leads to senescence and death. As an organism lives into advanced age, the cells within will attempt to abate age-related decline by enhancing the activity of cellular stress pathways. The regulation of cellular stress responses by transcription factors SKN-1/Nrf2 is a well characterized pathway in which cellular stress, particularly xenobiotic stress, is abated by SKN-1/Nrf2-mediated transcriptional activation of the Phase II detoxification pathway. However, SKN-1/Nrf2 also regulates a multitude of other processes including development, pathogenic stress responses, proteostasis, and lipid metabolism. While this process is typically tightly regulated, constitutive activation of SKN-1/Nrf2 is detrimental to organismal health, this raises interesting questions surrounding the tradeoff between SKN-1/Nrf2 cryoprotection and cellular health and the ability of cells to deactivate stress response pathways post stress. Recent work has determined that transcriptional programs of SKN-1 can be redirected or suppressed to abate negative health outcomes of constitutive activation. Here we will detail the mechanisms by which SKN-1 is controlled, which are important for our understanding of SKN-1/Nrf2 cytoprotection across the lifespan.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1369740"},"PeriodicalIF":3.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159584","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":"Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice.","authors":"Christopher B Forsyth, Maliha Shaikh, Phillip A Engen, Fabian Preuss, Ankur Naqib, Breanna A Palmen, Stefan J Green, Lijuan Zhang, Zlata R Bogin, Kristi Lawrence, Deepak Sharma, Garth R Swanson, Faraz Bishehsari, Robin M Voigt, Ali Keshavarzian","doi":"10.3389/fragi.2024.1352299","DOIUrl":"10.3389/fragi.2024.1352299","url":null,"abstract":"<p><p><b>Introduction:</b> Aging studies in humans and mice have played a key role in understanding the intestinal microbiome and an increased abundance of \"inflammaging\" Gram-negative (Gn) bacteria. The mechanisms underlying this inflammatory profile in the aging microbiome are unknown. We tested the hypothesis that an aging-related decrease in colonic crypt epithelial cell anti-microbial peptide (AMP) gene expression could promote colonic microbiome inflammatory Gn dysbiosis and inflammaging. <b>Methods:</b> As a model of aging, C57BL/6J mice fecal (colonic) microbiota (16S) and isolated colonic crypt epithelial cell gene expression (RNA-seq) were assessed at 2 months (mth) (human: 18 years old; yo), 15 mth (human: 50 yo), and 25 mth (human: 84 yo). Informatics examined aging-related microbial compositions, differential colonic crypt epithelial cell gene expressions, and correlations between colonic bacteria and colonic crypt epithelial cell gene expressions. <b>Results:</b> Fecal microbiota exhibited significantly increased relative abundances of pro-inflammatory Gn bacteria with aging. Colonic crypt epithelial cell gene expression analysis showed significant age-related downregulation of key AMP genes that repress the growth of Gn bacteria. The aging-related decrease in AMP gene expressions is significantly correlated with an increased abundance in Gn bacteria (dysbiosis), loss of colonic barrier gene expression, and senescence- and inflammation-related gene expression. <b>Conclusion:</b> This study supports the proposed model that aging-related loss of colonic crypt epithelial cell AMP gene expression promotes increased relative abundances of Gn inflammaging-associated bacteria and gene expression markers of colonic inflammaging. These data may support new targets for aging-related therapies based on intestinal genes and microbiomes.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1352299"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10945560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159700","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":"Identification of dihydromyricetin as a natural DNA methylation inhibitor with rejuvenating activity in human skin.","authors":"Cassandra Falckenhayn, Agata Bienkowska, Jörn Söhle, Katrin Wegner, Guenter Raddatz, Boris Kristof, Dirk Kuck, Ralf Siegner, Ronny Kaufmann, Julia Korn, Sascha Baumann, Daniela Lange, Andreas Schepky, Henry Völzke, Lars Kaderali, Marc Winnefeld, Frank Lyko, Elke Grönniger","doi":"10.3389/fragi.2023.1258184","DOIUrl":"10.3389/fragi.2023.1258184","url":null,"abstract":"<p><p>Changes in DNA methylation patterning have been reported to be a key hallmark of aged human skin. The altered DNA methylation patterns are correlated with deregulated gene expression and impaired tissue functionality, leading to the well-known skin aging phenotype. Searching for small molecules, which correct the aged methylation pattern therefore represents a novel and attractive strategy for the identification of anti-aging compounds. DNMT1 maintains epigenetic information by copying methylation patterns from the parental (methylated) strand to the newly synthesized strand after DNA replication. We hypothesized that a modest inhibition of this process promotes the restoration of the ground-state epigenetic pattern, thereby inducing rejuvenating effects. In this study, we screened a library of 1800 natural substances and 640 FDA-approved drugs and identified the well-known antioxidant and anti-inflammatory molecule dihydromyricetin (DHM) as an inhibitor of the DNA methyltransferase DNMT1. DHM is the active ingredient of several plants with medicinal use and showed robust inhibition of DNMT1 in biochemical assays. We also analyzed the effect of DHM in cultivated keratinocytes by array-based methylation profiling and observed a moderate, but significant global hypomethylation effect upon treatment. To further characterize DHM-induced methylation changes, we used published DNA methylation clocks and newly established age predictors to demonstrate that the DHM-induced methylation change is associated with a reduction in the biological age of the cells. Further studies also revealed re-activation of age-dependently hypermethylated and silenced genes <i>in vivo</i> and a reduction in age-dependent epidermal thinning in a 3-dimensional skin model. Our findings thus establish DHM as an epigenetic inhibitor with rejuvenating effects for aged human skin.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"4 ","pages":"1258184"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159583","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":"How are APOE4, changes in body weight, and longevity related? Insights from a causal mediation analysis.","authors":"Rachel Holmes, Hongzhe Duan, Olivia Bagley, Deqing Wu, Yury Loika, Alexander Kulminski, Anatoliy Yashin, Konstantin Arbeev, Svetlana Ukraintseva","doi":"10.3389/fragi.2024.1359202","DOIUrl":"10.3389/fragi.2024.1359202","url":null,"abstract":"<p><p>The ε4 allele of the APOE gene (<i>APOE4</i>) is known for its negative association with human longevity; however, the mechanism is unclear. <i>APOE4</i> is also linked to changes in body weight, and the latter changes were associated with survival in some studies. Here, we explore the role of aging changes in weight in the connection between <i>APOE4</i> and longevity using the causal mediation analysis (CMA) approach to uncover the mechanisms of genetic associations. Using the Health and Retirement Study (HRS) data, we tested a hypothesis of whether the association of <i>APOE4</i> with reduced survival to age 85+ is mediated by key characteristics of age trajectories of weight, such as the age at reaching peak values and the slope of the decline in weight afterward. Mediation effects were evaluated by the total effect (TE), natural indirect effect, and percentage mediated. The controlled direct effect and natural direct effect are also reported. The CMA results suggest that <i>APOE4</i> carriers have 19%-22% (TE <i>p</i> = 0.020-0.039) lower chances of surviving to age 85 and beyond, in part, because they reach peak values of weight at younger ages, and their weight declines faster afterward compared to non-carriers. This finding is in line with the idea that the detrimental effect of <i>APOE4</i> on longevity is, in part, related to the accelerated physical aging of ε4 carriers.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1359202"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140145045","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":"Dietary pyrroloquinoline quinone hinders aging progression in male mice and D-galactose-induced cells.","authors":"Nur Syafiqah Mohamad Ishak, Midori Kikuchi, Kazuto Ikemoto","doi":"10.3389/fragi.2024.1351860","DOIUrl":"10.3389/fragi.2024.1351860","url":null,"abstract":"<p><p><b>Background:</b> Understanding and promoting healthy aging has become a necessity in the modern world, where life expectancy is rising. The prospective benefits of the antioxidant pyrroloquinoline quinone (PQQ) in healthy aging are promising. However, its role in aging remains unclear. Thus, this study aimed to investigate the effect of PQQ on preventing the progression of aging and to explore its underlying molecular mechanisms. <b>Methods:</b> Naturally aged C57BL/6J male mice were fed a normal diet with or without PQQ (20 mg/kg/day) for 10 weeks. Body composition was measured by bioimpedance at weeks 0 and 8. The integument conditions were evaluated at weeks 0, 4, and 8. Muscle strength and function were examined at week 8. At the ninth week, computed tomography images of the mice were captured, and blood and tissue samples were collected. The levels of inflammatory cytokines in the gastrocnemius muscle were measured, and the muscle fiber cross-sectional area in the soleus muscle was examined. Additionally, a D-galactose (D-gal)-induced cell aging model was used to study the effects of PQQ intervention on cell proliferation, senescence, differentiation, ROS levels, and mitochondrial function in myoblasts (C2C12). Cell proliferation and monolayer permeability of D-gal-induced intestinal epithelial cells (IEC6) were also examined. <b>Results:</b> Aged mice suffered from malnutrition; however, PQQ supplementation ameliorated this effect, possibly by improving metabolic dysfunction and small intestinal performance. PQQ prevented rapid loss of body fat and body fluid accumulation, attenuated muscle atrophy and weakening, reduced chronic inflammation in skeletal muscles, and improved skin and coating conditions in aged mice. Furthermore, PQQ intervention in D-gal-treated C2C12 cells improved mitochondrial function, reduced cellular reactive oxygen species (ROS) levels and senescence, and enhanced cell differentiation, consequently preventing age-related muscle atrophy. In addition, PQQ increased cell proliferation in D-gal-treated IEC6 cells and consequently improved intestinal barrier function. <b>Conclusion:</b> PQQ could hinder the aging process and particularly attenuate muscle atrophy, and muscle weakness by improving mitochondrial function, leading to reduced age-related oxidative stress and inflammation in muscles. PQQ may also ameliorate malnutrition caused by intestinal barrier dysfunction by enhancing IEC proliferation. This study provides evidence for the role of PQQ in aging and suggests that PQQ may be a potential nutritional supplementation that can be included in healthy aging strategies.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":"5 ","pages":"1351860"},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10938241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133441","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}