Aging advances最新文献

{"title":"Mitoepigenetic Targeting of Age-Related Dysfunction: Mechanisms, Therapeutic Avenues, and Transgenerational Implications.","authors":"Kit Neikirk, Suraj Thapliyal, Sepiso K Masenga, Ashton Oliver, Margaret Mungai, Han Le, Heather K Beasley, Andrea G Marshall, Anthonya T Cooper, Taneisha Gillyard Cheairs, Benjamin I Rodriguez, Edgar Garza-Lopez, Prasanna Katti, Antentor Hinton","doi":"10.4103/agingadv.agingadv-d-25-00006","DOIUrl":"10.4103/agingadv.agingadv-d-25-00006","url":null,"abstract":"<p><p>Mitochondrial epigenetics, a burgeoning field bridging mitochondrial biology and epigenetic regulation, has emerged as a critical determinant of aging and age-related diseases. While nuclear epigenetics is well-characterized, the mechanisms governing mitochondrial DNA (mtDNA) regulation, including nucleoid dynamics, non-coding RNAs (ncRNAs), and metabolite-driven modifications, remain underexplored. This review synthesizes evidence that mitochondrial epigenetics influences cardiovascular pathogenesis through altered DNA methylation and histone acetylation patterns, which dysregulate oxidative phosphorylation and nucleoid stability. In neurodegenerative diseases, endoplasmic reticulum-mitochondrial contact points, disrupted by aging, impair calcium homeostasis and promote neuronal apoptosis, while oxidative stress exacerbates mtDNA instability through inefficient repair mechanisms. Cancer cells exploit mitochondrial metabolic reprogramming, where shifts in acetyl-CoA and α-ketoglutarate levels modulate epigenetic enzymes, fostering drug resistance. Potential therapeutic targets include pharmacological modulation of Mitochondrial transcription factor A acetylation/phosphorylation to enhance mtDNA transcription and dietary interventions to boost NAD+ levels, thereby improving mitochondrial function. Transgenerational studies reveal matrilineal inheritance of mtDNA methylation patterns and stress-induced epigenetic memory, though technical limitations in detecting mtDNA methylation persist. Clinically, mitochondrial epigenetic biomarkers like mtDNA hydroxymethylation and lncRNA expression (e.g., Mitoregulin) show promise for early diagnosis and treatment monitoring. Despite advances, challenges include standardizing methods for mtDNA methylation analysis and translating preclinical findings into therapies. This perspective review underscores the need for integrative approaches combining single-cell sequencing and CRISPR-based technologies to dissect mitochondrial-nuclear crosstalk, ultimately paving the way for precision medicine strategies targeting mitoepigenetic pathways to mitigate age-related decline.</p>","PeriodicalId":520381,"journal":{"name":"Aging advances","volume":"2 3","pages":"108-111"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088790","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":"Biological aging and its association with serum neurofilament light chain levels in middle-aged African Americans: a prospective observational study.","authors":"Man-Kit Lei, Mei Ling Ong, Ronald L Simons, Steven R H Beach","doi":"10.4103/agingadv.agingadv-d-24-00021","DOIUrl":"10.4103/agingadv.agingadv-d-24-00021","url":null,"abstract":"<p><p>This study examines the association between DNA methylation-based epigenetic aging indices and neurofilament light chain levels in middle-aged African Americans to advance the understanding of neurodegeneration and cognitive decline. Epigenetic aging was assessed in samples from 2008 and 2019 by applying HorvathAgeAccel, HannumAgeAccel, PhenoAgeAccel, GrimAgeAccel, and DunedinPACE. Controlling for financial strain, exercise, age, gender, cell-type composition, and <i>APOE-ε4</i>, second- and third-generation DNA methylation-based aging-PhenoAgeAccel, GrimAgeAccel, and DunedinPACE-were significantly associated with serum neurofilament light chain levels. In contrast, first-generation DNA methylation-based clocks, including HorvathAgeAccel and HannumAgeAccel, were not significantly related to neurofilament light chain. These findings suggest that newer DNA methylation-based aging indices are more strongly associated with neurodegenerative biomarkers. Integrating advanced DNA methylation-based clocks with neurofilament light chain levels may improve early detection of cognitive decline and dementia, supporting personalized medicine by identifying biological aging profiles linked to neurodegenerative risks.</p>","PeriodicalId":520381,"journal":{"name":"Aging advances","volume":"2 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187970","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":"N-lactoyl phenylalanine suppresses appetite and obesity with important implications for aging and age-related diseases.","authors":"Antentor Hinton, Kit Neikirk, Han Le, Ashton Oliver, Chanel Harris, Pamela Martin, Amadou Gaye","doi":"10.4103/agingadv.agingadv-d-24-00011","DOIUrl":"10.4103/agingadv.agingadv-d-24-00011","url":null,"abstract":"","PeriodicalId":520381,"journal":{"name":"Aging advances","volume":"1 2","pages":"172-173"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026270","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":"Estrogen receptors in mitochondrial metabolism: age-related changes and implications for pregnancy complications.","authors":"Antentor Hinton, Kit Neikirk, Han Le, Chanel Harris, Ashton Oliver, Pamela Martin, Amadou Gaye","doi":"10.4103/agingadv.agingadv-d-24-00012","DOIUrl":"10.4103/agingadv.agingadv-d-24-00012","url":null,"abstract":"<p><p>Estrogen hormones are primarily associated with their role as female sex hormones responsible for primary and secondary sexual development. Estrogen receptors are known to undergo age-dependent decreases due to age-related changes in hormone production. In the mitochondria, estrogen functions by reducing the production of reactive oxygen species in the electron transport chain, inhibiting apoptosis, and regulating mitochondrial DNA content. Moreover, estrogen receptors may be the key components in maintaining mitochondrial membrane potential and structure. Although estrogen plays a crucial role in the development of pregnancy, our understanding of how estrogen receptors change with aging during pregnancy remains limited. During pregnancy, estrogen levels are significantly elevated, with a corresponding upregulation of estrogen receptors, which play various roles in pregnancy. However, the exact role of estrogen receptors in pregnancy complications remains to be further investigated. The paper reviews the role of estrogen receptors in the regulation of mitochondrial metabolism and in pregnancy complications, with a special focus on the effect of age-related changes on estrogen levels and estrogen receptors function. We also address how estrogen maintains mitochondrial function, including reducing the production of reactive oxygen species in the electron transport chain, inhibiting apoptosis, regulating mitochondrial DNA content, and maintaining mitochondrial membrane potential and structure. However, the effects of estrogen on mitochondria-endoplasmic reticulum contacts have not been well studied. Based on these emergent roles in mitochondria, the differential roles of estrogen receptors in pregnancy complications are of great relevance. The paper emphasizes the association between maternal health and estrogen receptors and indicates the need for future research to elucidate the interdependence of estrogen receptor-regulated maternal health with mitochondrial function and their relationship with the gut microbiome. Overall, we summarize the important role of estrogen receptors during pregnancy and highlight the need for further research to better understand the role of estrogen receptors in aging and pregnancy complications. This not only helps to reveal the mechanism underlying the role of estrogen in maternal health but also has potential clinical implications for the development of new therapies targeting age-related diseases and pregnancy complications.</p>","PeriodicalId":520381,"journal":{"name":"Aging advances","volume":"1 2","pages":"154-171"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019978","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}