Aging Cell最新文献_第9页

Humanin P3S, haplogroup N1b and the risk of Alzheimer's disease 人类蛋白 P3S、单倍群 N1b 与阿尔茨海默病的风险。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-17 DOI: 10.1111/acel.14207

Ian Stewart Logan

{"title":"Humanin P3S, haplogroup N1b and the risk of Alzheimer's disease","authors":"Ian Stewart Logan","doi":"10.1111/acel.14207","DOIUrl":"10.1111/acel.14207","url":null,"abstract":"A commentary of the paper ‘Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4-induced brain pathology’ that appeared recently in Aging Cell. The possible association of a mitochondrial haplogroup with a disease is frequently discussed. The Humanin peptide encoded by the mtDNA has been shown to play an important regulatory role in cell metabolism. There are variants of Humanin caused by different mutations and it is known that the potent form of Humanin, termed S14G, is found naturally in the people of haplogroup U6a7a1a because they have the mutation m.A2672G; however it has not been shown that having this mutation is indeed beneficial. In their paper, the authors suggest that the mitochondrial DNA mutation, m.C2639T, may be beneficial in people who are in haplogroup N1b and also carry APOE4. The mutation changes the common form of Humanin to Humanin P3S. In the study, the researchers looked at a group of Ashkenazi women who were over the age of 95, and found that a higher proportion of them carried APOE4, suggesting that Humanin P3S protected them against the adverse effects of APOE4. A study in a mouse model supported this finding by showing treatment with Humanin P3S reduced APOE4-induced brain pathology. In the world population, there are about 500,000 Ashkenazi in haplogroup N1b, predominantly in the subgroup N1b1b1; and there are about 9.5 million non-Ashkenazi people with the mutation m.C2639T and are therefore also in haplogroup N1b and have Humanin P3S. However, the researchers have yet to show Humanin P3S is of benefit in non-Ashkenazi people. This paper raises the possibility of a therapeutic use of Humanin P3S in the treatment of Alzheimer's disease.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aging-associated decrease of PGC-1α promotes pain chronification 与衰老相关的PGC-1α的减少促进了疼痛的慢性化。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-17 DOI: 10.1111/acel.14177

Xinbo Wu, Liuyue Yang, Zihua Li, Chenzheng Gu, Kaiyan Jin, Andrew Luo, Nabeel Faiyaz Rasheed, Isabella Fiutak, Kristina Chao, Amy Chen, Jianren Mao, Qian Chen, Weihua Ding, Shiqian Shen

{"title":"Aging-associated decrease of PGC-1α promotes pain chronification","authors":"Xinbo Wu, Liuyue Yang, Zihua Li, Chenzheng Gu, Kaiyan Jin, Andrew Luo, Nabeel Faiyaz Rasheed, Isabella Fiutak, Kristina Chao, Amy Chen, Jianren Mao, Qian Chen, Weihua Ding, Shiqian Shen","doi":"10.1111/acel.14177","DOIUrl":"10.1111/acel.14177","url":null,"abstract":"Aging is generally associated with declining somatosensory function, which seems at odds with the high prevalence of chronic pain in older people. This discrepancy is partly related to the high prevalence of degenerative diseases such as osteoarthritis in older people. However, whether aging alters pain processing in the primary somatosensory cortex (S1), and if so, whether it promotes pain chronification is largely unknown. Herein, we report that older mice displayed prolonged nociceptive behavior following nerve injury when compared with mature adult mice. The expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) in S1 was decreased in older mice, whereas PGC-1α haploinsufficiency promoted prolonged nociceptive behavior after nerve injury. Both aging and PGC-1α haploinsufficiency led to abnormal S1 neural dynamics, revealed by intravital two-photon calcium imaging. Manipulating S1 neural dynamics affected nociceptive behavior after nerve injury: chemogenetic inhibition of S1 interneurons aggravated nociceptive behavior in naive mice; chemogenetic activation of S1 interneurons alleviated nociceptive behavior in older mice. More interestingly, adeno-associated virus-mediated expression of PGC-1α in S1 interneurons ameliorated aging-associated chronification of nociceptive behavior as well as aging-related S1 neural dynamic changes. Taken together, our results showed that aging-associated decrease of PGC-1α promotes pain chronification, which might be harnessed to alleviate the burden of chronic pain in older individuals.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elimination of damaged mitochondria during UVB-induced senescence is orchestrated by NIX-dependent mitophagy 在紫外线诱导的衰老过程中，受损线粒体的消除是由依赖于 NIX 的有丝分裂协调进行的。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-17 DOI: 10.1111/acel.14186

Maria Cavinato, Ines Martic, Sophia Wedel, Annabella Pittl, Rafal Koziel, Regina Weinmmüllner, Markus Schosserer, Brigitte Jenewein, Madhusudhan Reddy Bobbili, Elsa Arcalis, Johannes Haybaeck, Gerhard Pierer, Christian Ploner, Martin Hermann, Nikolaus Romani, Matthias Schmuth, Johannes Grillari, Pidder Jansen-Dürr

{"title":"Elimination of damaged mitochondria during UVB-induced senescence is orchestrated by NIX-dependent mitophagy","authors":"Maria Cavinato, Ines Martic, Sophia Wedel, Annabella Pittl, Rafal Koziel, Regina Weinmmüllner, Markus Schosserer, Brigitte Jenewein, Madhusudhan Reddy Bobbili, Elsa Arcalis, Johannes Haybaeck, Gerhard Pierer, Christian Ploner, Martin Hermann, Nikolaus Romani, Matthias Schmuth, Johannes Grillari, Pidder Jansen-Dürr","doi":"10.1111/acel.14186","DOIUrl":"10.1111/acel.14186","url":null,"abstract":"Skin aging is the result of two types of aging, “intrinsic aging” an inevitable consequence of physiologic and genetically determined changes and “extrinsic aging,” which is dependent on external factors such as exposure to sunlight, smoking, and dietary habits. UVB causes skin injury through the generation of free radicals and other oxidative byproducts, also contributing to DNA damage. Appearance and accumulation of senescent cells in the skin are considered one of the hallmarks of aging in this tissue. Mitochondria play an important role for the development of cellular senescence, in particular stress-induced senescence of human cells. However, many aspects of mitochondrial physiology relevant to cellular senescence and extrinsic skin aging remain to be unraveled. Here, we demonstrate that mitochondria damaged by UVB irradiation of human dermal fibroblasts (HDF) are eliminated by NIX-dependent mitophagy and that this process is important for cell survival under these conditions. Additionally, UVB-irradiation of human dermal fibroblasts (HDF) induces the shedding of extracellular vesicles (EVs), and this process is significantly enhanced in UVB-irradiated NIX-depleted cells. Our findings establish NIX as the main mitophagy receptor in the process of UVB-induced senescence and suggest the release of EVs as an alternative mechanism of mitochondrial quality control in HDF.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status 羟基柠檬酸盐可延缓小鼠早期死亡，促进肌肉再生，同时诱导丰富的肝脏能量状态。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-17 DOI: 10.1111/acel.14205

Isabel Espadas, María Ángeles Cáliz-Molina, Raúl López-Fernández-Sobrino, Concepción Panadero-Morón, Alejandro Sola-García, Mario Soriano-Navarro, Enrique Martínez-Force, Mónica Venegas-Calerón, Joaquin J. Salas, Franz Martín, Benoit R. Gauthier, Clara Alfaro-Cervelló, David Martí-Aguado, Vivian Capilla-González, Alejandro Martín-Montalvo

{"title":"Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status","authors":"Isabel Espadas, María Ángeles Cáliz-Molina, Raúl López-Fernández-Sobrino, Concepción Panadero-Morón, Alejandro Sola-García, Mario Soriano-Navarro, Enrique Martínez-Force, Mónica Venegas-Calerón, Joaquin J. Salas, Franz Martín, Benoit R. Gauthier, Clara Alfaro-Cervelló, David Martí-Aguado, Vivian Capilla-González, Alejandro Martín-Montalvo","doi":"10.1111/acel.14205","DOIUrl":"10.1111/acel.14205","url":null,"abstract":"ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy-fed mice, and improved locomotion in mice exposed to cardiotoxin-induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-16 DOI: 10.1111/acel.14200

Marcus Dittrich, Laura Bernhardt, Christopher A. Penfold, Thorsten E. Boroviak, Charis Drummer, Rüdiger Behr, Tobias Müller, Thomas Haaf

{"title":"Age-related and species-specific methylation changes in the protein-coding marmoset sperm epigenome","authors":"Marcus Dittrich, Laura Bernhardt, Christopher A. Penfold, Thorsten E. Boroviak, Charis Drummer, Rüdiger Behr, Tobias Müller, Thomas Haaf","doi":"10.1111/acel.14200","DOIUrl":"10.1111/acel.14200","url":null,"abstract":"The sperm epigenome is thought to affect the developmental programming of the resulting embryo, influencing health and disease in later life. Age-related methylation changes in the sperm of old fathers may mediate the increased risks for reproductive and offspring medical problems. The impact of paternal age on sperm methylation has been extensively studied in humans and, to a lesser extent, in rodents and cattle. Here, we performed a comparative analysis of paternal age effects on protein-coding genes in the human and marmoset sperm methylomes. The marmoset has gained growing importance as a non-human primate model of aging and age-related diseases. Using reduced representation bisulfite sequencing, we identified age-related differentially methylated transcription start site (ageTSS) regions in 204 marmoset and 27 human genes. The direction of methylation changes was the opposite, increasing with age in marmosets and decreasing in humans. None of the identified ageTSS was differentially methylated in both species. Although the average methylation levels of all TSS regions were highly correlated between marmosets and humans, with the majority of TSS being hypomethylated in sperm, more than 300 protein-coding genes were endowed with species-specifically (hypo)methylated TSS. Several genes of the glycosphingolipid (GSL) biosynthesis pathway, which plays a role in embryonic stem cell differentiation and regulation of development, were hypomethylated (<5%) in human and fully methylated (>95%) in marmoset sperm. The expression levels and patterns of defined sets of GSL genes differed considerably between human and marmoset pre-implantation embryo stages and blastocyst tissues, respectively.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LEMD2-associated progeroid syndrome: Expanding the phenotype of the nuclear envelopathy caused by a defect in LEMD2 gene LEMD2相关早衰综合征：扩展由 LEMD2 基因缺陷引起的核包膜病变的表型。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-16 DOI: 10.1111/acel.14189

Alyssia Matter, Christina Kaufman, Nadia Zürcher, Daniela Lenggenhager, Patrice Grehten, Deborah Bartholdi, Laura Horka, Johannes Häberle, Georgios Makris

{"title":"LEMD2-associated progeroid syndrome: Expanding the phenotype of the nuclear envelopathy caused by a defect in LEMD2 gene","authors":"Alyssia Matter, Christina Kaufman, Nadia Zürcher, Daniela Lenggenhager, Patrice Grehten, Deborah Bartholdi, Laura Horka, Johannes Häberle, Georgios Makris","doi":"10.1111/acel.14189","DOIUrl":"10.1111/acel.14189","url":null,"abstract":"Nuclear envelopathies are rare genetic diseases that compromise the integrity of the nuclear envelope. Patients with a defect in LEM domain nuclear envelope protein 2 (LEMD2) leading to LEMD2-associated progeroid syndrome are exceedingly scarce in number, yet they exhibit shared clinical features including skeletal abnormalities and a prematurely-aged appearance. Our study broadens the understanding of LEMD2-associated progeroid syndrome by detailing its phenotypic and molecular characteristics in the first female and fourth reported case, highlighting a distinct impact on metabolic functions. The patient's history revealed growth delay, facial and skeletal abnormalities, and recurrent abdominal pain crises caused by hepatomegaly. Comparisons with the previously documented cases emphasized similarities in skeletal and facial features while showcasing unique variations, notably in cardiac and hepatic manifestations. In vitro experiments conducted on patient-derived peripheral blood and urinary epithelial cells and LEMD2-downregulated HepG2 cells confirmed abnormalities in the structure of the nuclear envelope in all three tissue-types. Overall, our work offers a comprehensive profile of a patient with LEMD2-related syndrome, emphasizing the hepatic involvement in the disease and broadening our understanding of clinical and molecular implications. This study not only contributes specific insights into LEMD2-related conditions but also underscores potential therapeutic paths for disorders affecting nuclear envelope dynamics.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The integrated stress response promotes neural stem cell survival under conditions of mitochondrial dysfunction in neurodegeneration 在神经退行性疾病线粒体功能障碍的条件下，综合应激反应可促进神经干细胞存活。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-16 DOI: 10.1111/acel.14165

Mohamed Ariff Iqbal, Maria Bilen, Yubing Liu, Vanessa Jabre, Bensun C. Fong, Imane Chakroun, Smitha Paul, Jingwei Chen, Steven Wade, Michel Kanaan, Mary-Ellen Harper, Mireille Khacho, Ruth S. Slack

{"title":"The integrated stress response promotes neural stem cell survival under conditions of mitochondrial dysfunction in neurodegeneration","authors":"Mohamed Ariff Iqbal, Maria Bilen, Yubing Liu, Vanessa Jabre, Bensun C. Fong, Imane Chakroun, Smitha Paul, Jingwei Chen, Steven Wade, Michel Kanaan, Mary-Ellen Harper, Mireille Khacho, Ruth S. Slack","doi":"10.1111/acel.14165","DOIUrl":"10.1111/acel.14165","url":null,"abstract":"Impaired mitochondrial function is a hallmark of aging and a major contributor to neurodegenerative diseases. We have shown that disrupted mitochondrial dynamics typically found in aging alters the fate of neural stem cells (NSCs) leading to impairments in learning and memory. At present, little is known regarding the mechanisms by which neural stem and progenitor cells survive and adapt to mitochondrial dysfunction. Using Opa1-inducible knockout as a model of aging and neurodegeneration, we identify a decline in neurogenesis due to impaired stem cell activation and progenitor proliferation, which can be rescued by the mitigation of oxidative stress through hypoxia. Through sc-RNA-seq, we identify the ATF4 pathway as a critical mechanism underlying cellular adaptation to metabolic stress. ATF4 knockdown in Opa1-deficient NSCs accelerates cell death, while the increased expression of ATF4 enhances proliferation and survival. Using a Slc7a11 mutant, an ATF4 target, we show that ATF4-mediated glutathione production plays a critical role in maintaining NSC survival and function under stress conditions. Together, we show that the activation of the integrated stress response (ISR) pathway enables NSCs to adapt to metabolic stress due to mitochondrial dysfunction and metabolic stress and may serve as a therapeutic target to enhance NSC survival and function in aging and neurodegeneration.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exercise rejuvenates microglia and reverses T cell accumulation in the aged female mouse brain 运动能使小胶质细胞恢复活力，并逆转老年雌鼠大脑中 T 细胞的积累。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-15 DOI: 10.1111/acel.14172

Solal Chauquet, Emily F. Willis, Laura Grice, Samuel B. R. Harley, Joseph E. Powell, Naomi R. Wray, Quan Nguyen, Marc J. Ruitenberg, Sonia Shah, Jana Vukovic

{"title":"Exercise rejuvenates microglia and reverses T cell accumulation in the aged female mouse brain","authors":"Solal Chauquet, Emily F. Willis, Laura Grice, Samuel B. R. Harley, Joseph E. Powell, Naomi R. Wray, Quan Nguyen, Marc J. Ruitenberg, Sonia Shah, Jana Vukovic","doi":"10.1111/acel.14172","DOIUrl":"10.1111/acel.14172","url":null,"abstract":"Slowing and/or reversing brain ageing may alleviate cognitive impairments. Previous studies have found that exercise may mitigate cognitive decline, but the mechanisms underlying this remain largely unclear. Here we provide unbiased analyses of single-cell RNA sequencing data, showing the impacts of exercise and ageing on specific cell types in the mouse hippocampus. We demonstrate that exercise has a profound and selective effect on aged microglia, reverting their gene expression signature to that of young microglia. Pharmacologic depletion of microglia further demonstrated that these cells are required for the stimulatory effects of exercise on hippocampal neurogenesis but not cognition. Strikingly, allowing 18-month-old mice access to a running wheel did by and large also prevent and/or revert T cell presence in the ageing hippocampus. Taken together, our data highlight the profound impact of exercise in rejuvenating aged microglia, associated pro-neurogenic effects and on peripheral immune cell presence in the ageing female mouse brain.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults 蛋白质组衰老时钟（PAC）可预测中老年人与年龄相关的结果。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-15 DOI: 10.1111/acel.14195

Chia-Ling Kuo, Zhiduo Chen, Peiran Liu, Luke C. Pilling, Janice L. Atkins, Richard H. Fortinsky, George A. Kuchel, Breno S. Diniz

{"title":"Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults","authors":"Chia-Ling Kuo, Zhiduo Chen, Peiran Liu, Luke C. Pilling, Janice L. Atkins, Richard H. Fortinsky, George A. Kuchel, Breno S. Diniz","doi":"10.1111/acel.14195","DOIUrl":"10.1111/acel.14195","url":null,"abstract":"Beyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features of biological aging and might, therefore, offer useful information for the testing and, ultimately, clinical use of gerotherapeutics. We aimed to develop a proteomic aging clock (PAC) for all-cause mortality risk as a proxy of biological age. Data were from the UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 and 70 years and 2923 plasma proteins assessed using the Olink Explore 3072 assay®. 10.9% of the participants died during a mean follow-up of 13.3 years, with the mean age at death of 70.1 years. The Spearman correlation between PAC proteomic age and chronological age was 0.77. PAC showed robust age-adjusted associations and predictions for all-cause mortality and the onset of various diseases in general and disease-free participants. The proteins associated with PAC proteomic age deviation were enriched in several processes related to the hallmarks of biological aging. Our results expand previous findings by showing that biological age acceleration, based on PAC, strongly predicts all-cause mortality and several incident disease outcomes. Particularly, it facilitates the evaluation of risk for multiple conditions in a disease-free population, thereby, contributing to the prevention of initial diseases, which vary among individuals and may subsequently lead to additional comorbidities.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circulating microRNA profile of long-lived Okinawans identifies novel potential targets for optimizing lifespan and health span 长寿冲绳人的循环 microRNA 图谱确定了优化寿命和健康寿命的潜在新目标。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-05-15 DOI: 10.1111/acel.14191

Sarah Noureddine, Augusto Schneider, Sydney Strader, Xiang Zhu, Joseph Dhahbi, Richard Allsopp, D. Craig Willcox, Timothy A. Donlon, Michio Shimabukuro, Moritake Higa, Makoto Suzuki, Trevor Torigoe, Sarah Ashiqueali, Hariom Yadav, Bradley J. Willcox, Michal M. Masternak

{"title":"Circulating microRNA profile of long-lived Okinawans identifies novel potential targets for optimizing lifespan and health span","authors":"Sarah Noureddine, Augusto Schneider, Sydney Strader, Xiang Zhu, Joseph Dhahbi, Richard Allsopp, D. Craig Willcox, Timothy A. Donlon, Michio Shimabukuro, Moritake Higa, Makoto Suzuki, Trevor Torigoe, Sarah Ashiqueali, Hariom Yadav, Bradley J. Willcox, Michal M. Masternak","doi":"10.1111/acel.14191","DOIUrl":"10.1111/acel.14191","url":null,"abstract":"Nonagenarians and centenarians serve as successful examples of aging and extended longevity, showcasing robust regulation of biological mechanisms and homeostasis. Given that human longevity is a complex field of study that navigates molecular and biological mechanisms influencing aging, we hypothesized that microRNAs, a class of small noncoding RNAs implicated in regulating gene expression at the post-transcriptional level, are differentially regulated in the circulatory system of young, middle-aged, and nonagenarian individuals. We sequenced circulating microRNAs in Okinawan males and females <40, 50–80, and >90 years of age accounting for FOXO3 genetic variations of single nucleotide polymorphism (SNP) rs2802292 (TT - common vs. GT - longevity) and validated the findings through RT-qPCR. We report five microRNAs exclusively upregulated in both male and female nonagenarians with the longevity genotype, play predictive functional roles in TGF-β, FoxO, AMPK, Pi3K-Akt, and MAPK signaling pathways. Our findings suggest that these microRNAs upregulated in nonagenarians may provide novel insight into enhanced lifespan and health span. This discovery warrants further exploration into their roles in human aging and longevity.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0