{"title":"Association between arterial stiffness index and age-related diseases: A Mendelian randomization study.","authors":"Xiaojie Yu,Yang Cao,Xinyi Li,Qingchun Liang,Xiaodan Dong,Bing Liang","doi":"10.1089/rej.2024.0041","DOIUrl":"https://doi.org/10.1089/rej.2024.0041","url":null,"abstract":"Arterial stiffness is an emerging indicator of cardiovascular risk, but its causal relationship with a variety of age-related diseases is unclear. Objective is to assess the causal relationship between arterial stiffness index (ASI) and age-related diseases by Mendelian randomization (MR) analysis. We obtained instrumental variables associated with age-related diseases from genome-wide association studies (GWAS) of 484,598 European individuals, and data for ASI were obtained from the UK Biobank GWAS of 127,127 participants. We used the inverse variance-weighted (IVW) as the primary analysis method. In addition, several sensitivity analyses including MR-Egger, weighted-median (WM), MR-PRESSO and Cochran's Q test were performed to test the robustness of the results. Reverse MR analysis were also performed to assess reverse Causal relationships between age-related diseases and ASI. We verified causal relationship between eight age-related diseases and ASI, of which cardiovascular disease, gallbladder disease, Liver, biliary or pancreas problem, hypertension, joint disorder and esophageal disorder elevated ASI. In contrast, hyperthyroidism or thyrotoxicosis and bowel problem may reduce ASI. This MR analysis reveals causal relationships between ASI and several age-related diseases. ASI is expected to be a potential indicator of health conditions for older populations.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"50 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Zhang,Kai Gao,Ya Bai,Dong Xu,Meina Zhao,Xingru Tao,Jingwen Wang
{"title":"Wedelolactone attenuates liver fibrosis and hepatic stellate cell activation by suppressing the Hippo pathway.","authors":"Wei Zhang,Kai Gao,Ya Bai,Dong Xu,Meina Zhao,Xingru Tao,Jingwen Wang","doi":"10.1089/rej.2024.0053","DOIUrl":"https://doi.org/10.1089/rej.2024.0053","url":null,"abstract":"Liver fibrosis is a commonly observed pathological phenomenon that occurs during the progression of various types of chronic liver diseases. The Hippo pathway is closely associated with the pathogenesis of liver fibrosis. Previous studies have shown that wedelolactone (WED) has a significant anti-hepatic fibrosis effect, whereas the target and mechanism underlying WED remain elusive. In this study, we found that WED significantly alleviated liver fibrosis and injury by inhibiting the expression of YAP and TAZ. In an in vitro model, WED suppressed the activation of hepatic stellate cells (HSCs) induced by TGF-β1, as well as the mRNA and protein expression of α-SMA, YAP, and TAZ. The allosteric regulation of YAP by WED was confirmed using MD and CETSA. Moreover, specific knockdown or inhibition of YAP did not enhance the suppressive effect of WED on HSC activation or protein expression associated with fibrosis. These findings demonstrated that the administration of WED effectively alleviated liver fibrosis by suppressing the Hippo/YAP/TAZ pathways. In addition, YAP activity may be regulated by WED via allosteric regulation.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"54 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rejuvenation researchPub Date : 2023-10-01Epub Date: 2023-09-25DOI: 10.1089/rej.2023.0035
Victor A Ansere, Matthew P Bubak, Benjamin F Miller, Willard M Freeman
{"title":"Heterochronic Plasma Transfer: Experimental Design, Considerations, and Technical Challenges.","authors":"Victor A Ansere, Matthew P Bubak, Benjamin F Miller, Willard M Freeman","doi":"10.1089/rej.2023.0035","DOIUrl":"10.1089/rej.2023.0035","url":null,"abstract":"<p><p>Experimental approaches such as Heterochronic Plasma Transfer (HPT) provide insights into the aging process and help identify the factors that impact aging, with the aim of developing anti-aging therapies. HPT involves the transfer of plasma from an animal of one age to an animal of a different age and highlights the effects of the systemic environment on aging. Despite its importance as an aging research tool, HPT is not without limitations and HPT experiments across various studies differ in key experimental designs considerations, presenting a challenge in obtaining comparable outcomes. In this review, we examine the caveats and experimental design considerations of HPT as a research tool. We provide insights into plasma preparation procedures, route of administration, dosing regimen, and appropriate controls to assist investigators in achieving their experimental goals.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":"171-179"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10667024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dirceu de Sousa Melo, Liliane Costa-Pereira, Carina Sousa Santos, Bruno Ferreira Mendes, Isaac Konig, Bruna Chaves Garcia, Ilkilene Queiroz, Lauane Gomes Moreno, Ricardo Cardoso Cassilhas, Elizabethe Adriana Esteves, Etel Vieira Rocha, Flávio Castro Magalhães, Luciano Dos Santos Aggum Capettini, Ricardo Augusto Leoni, Kinulpe Sampaio, Marco Fabrício Dias-Peixoto
{"title":"Intense Caloric Restriction from Birth Prevents Cardiovascular Aging in Rats.","authors":"Dirceu de Sousa Melo, Liliane Costa-Pereira, Carina Sousa Santos, Bruno Ferreira Mendes, Isaac Konig, Bruna Chaves Garcia, Ilkilene Queiroz, Lauane Gomes Moreno, Ricardo Cardoso Cassilhas, Elizabethe Adriana Esteves, Etel Vieira Rocha, Flávio Castro Magalhães, Luciano Dos Santos Aggum Capettini, Ricardo Augusto Leoni, Kinulpe Sampaio, Marco Fabrício Dias-Peixoto","doi":"10.1089/rej.2023.0032","DOIUrl":"10.1089/rej.2023.0032","url":null,"abstract":"<p><p>We previously demonstrated that a 50% caloric restriction (CR) from birth improves several cardiometabolic risk factors in young rats. In this study, we investigated in middle-aged rats the consequences of a 50% CR from birth on cardiometabolic risk factors, heart function/morphology, ventricular arrhythmia, and fibrillation incidence, and cardiac intracellular proteins involved with redox status and cell survival. From birth to the age of 18 months, rats were divided into an <i>Ad Libitum</i> (AL18) group, which had free access to food, and a CR18 group, which had food limited to 50% of that consumed by the AL18. Resting metabolic rate, blood pressure, and heart rate were recorded, and oral glucose and intraperitoneal insulin tolerance tests were performed. Blood was collected for biochemical analyses, and visceral fat and liver were harvested and weighed. Hearts were harvested for cardiac function, histological, redox status, and western blot analyses. The 50% CR from birth potentially reduced several cardiometabolic risk factors in 18-month-old rats. Moreover, compared with AL18, the CR18 group showed a ∼50% increase in cardiac contractility and relaxation, nearly three to five times less incidence of ventricular arrhythmia and fibrillation, ∼18% lower cardiomyocyte diameter, and ∼60% lower cardiac fibrosis. CR18 hearts also improved biomarkers of antioxidant defense and cell survival. Collectively, these results reveal several metabolic and cardiac antiaging effects of a 50% CR from birth in middle-aged rats.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":"194-205"},"PeriodicalIF":2.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10257689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rejuvenation researchPub Date : 2023-10-01Epub Date: 2023-10-05DOI: 10.1089/rej.2023.0019
Mariana Moysés-Oliveira, Luana Adami, Pedro Guerreiro, Amanda Mosini, Anna Kloster, Lais Cunha, Mayara Paschalidis, Bruna Pereira Marquezini, Gabriel Pires, Priscila Tempaku, Monica Andersen, Sergio Tufik
{"title":"Endocrine and Epigenetic Regulation as Common Pathways Underlying the Genetic Basis of Sleep Traits and Longevity.","authors":"Mariana Moysés-Oliveira, Luana Adami, Pedro Guerreiro, Amanda Mosini, Anna Kloster, Lais Cunha, Mayara Paschalidis, Bruna Pereira Marquezini, Gabriel Pires, Priscila Tempaku, Monica Andersen, Sergio Tufik","doi":"10.1089/rej.2023.0019","DOIUrl":"10.1089/rej.2023.0019","url":null,"abstract":"<p><p>The amount of sleep needed over one's lifespan is age dependent and not sleeping enough or sleeping in excess is associated with increased morbidity and mortality. Yet, the convergent molecular mechanisms that link longevity and sleep are largely unknown. We performed a gene enrichment study that (1) identified genes associated with both longevity and sleep traits and (2) determined molecular pathways enriched among these shared genes. We manually curated two sets of genes, one associated with longevity and aging and the other with sleep traits (<i>e.g.,</i> insomnia, narcolepsy, sleep duration, chronotype, among others), with both gene lists heavily driven by hits from recent large-scale Genome-Wide Association Studies. There were 47 overlapping genes between the gene list associated with sleep traits (1064 genes total) and the genes associated with longevity (367 genes total), indicating significantly more overlap than expected by chance. An overrepresentation analysis identified enriched pathways that suggest endocrine and epigenetic regulation as potential shared mechanisms between sleep traits and longevity. Concordantly, functional network analysis retrieved two clusters, being one associated with proteins of nuclear functions and the other, with extracellular proteins. This overlapping gene set, and the highlighted biological pathways may serve as preliminary findings for new functional investigations of sleep and longevity shared genetic mechanisms.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":"206-213"},"PeriodicalIF":2.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10554371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rejuvenation researchPub Date : 2023-10-01Epub Date: 2023-09-12DOI: 10.1089/rej.2023.0022
Amir Arav, Shujun Li, Or Friedman, Inna Solodeev, Jessie Aouizerate, Daniel Kedar, Marie De Antonio, Dity Natan, Eyal Gur, Nir Shani
{"title":"Long-Term Survival and Functional Recovery of Cryopreserved Vascularized Groin Flap and Below-the-Knee Rat Limb Transplants.","authors":"Amir Arav, Shujun Li, Or Friedman, Inna Solodeev, Jessie Aouizerate, Daniel Kedar, Marie De Antonio, Dity Natan, Eyal Gur, Nir Shani","doi":"10.1089/rej.2023.0022","DOIUrl":"10.1089/rej.2023.0022","url":null,"abstract":"<p><p>Effective cryopreservation of large tissues, limbs, and organs has the potential to revolutionize medical post-trauma reconstruction options and organ preservation and transplantation procedures. To date, vitrification and directional freezing are the only viable methods for long-term organ or tissue preservation, but are of limited clinical relevance. This work aimed to develop a vitrification-based approach that will enable the long-term survival and functional recovery of large tissues and limbs following transplantation. The presented novel two-stage cooling process involves rapid specimen cooling to subzero temperatures, followed by gradual cooling to the vitrification solution (VS) and tissue glass transition temperature. Flap cooling and storage were only feasible at temperatures equal to or slightly lower than the VS Tg (<i>i.e.</i>, -135°C). Vascularized rat groin flaps and below-the-knee (BTK) hind limb transplants cryopreserved using this approach exhibited long-term survival (>30 days) following transplantation to rats. BTK-limb recovery included hair regrowth, normal peripheral blood flow, and normal skin, fat, and muscle histology. Above all, BTK limbs were reinnervated, enabling rats to sense pain in the cryopreserved limb. These findings provide a strong foundation for the development of a long-term large-tissue, limb and organ preservation protocol for clinical use.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":"180-193"},"PeriodicalIF":2.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10215450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rejuvenation researchPub Date : 2023-08-01Epub Date: 2023-06-12DOI: 10.1089/rej.2023.0015
Kwasi Adu-Berchie, Favour O Obuseh, David J Mooney
{"title":"T Cell Development and Function.","authors":"Kwasi Adu-Berchie, Favour O Obuseh, David J Mooney","doi":"10.1089/rej.2023.0015","DOIUrl":"10.1089/rej.2023.0015","url":null,"abstract":"<p><p>T cells play critical roles in the immune system, including in responses to cancer, autoimmunity, and tissue regeneration. T cells arise from common lymphoid progenitors (CLPs) that differentiate from hematopoietic stem cells in the bone marrow. CLPs then traffic to the thymus, where they undergo thymopoiesis through a number of selection steps, resulting in mature single positive naive CD4 helper or CD8 cytotoxic T cells. Naive T cells are home to secondary lymphoid organs like lymph nodes and are primed by antigen-presenting cells, which scavenge for both foreign and self-antigens. Effector T cell function is multifaceted, including direct target cell lysis and secretion of cytokines, which regulate the functions of other immune cells (refer to \"Graphical Abstract\"). This review will discuss T cell development and function, from the development of lymphoid progenitors in the bone marrow to principles that govern T cell effector function and dysfunction, specifically within the context of cancer.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"26 4","pages":"126-138"},"PeriodicalIF":2.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10101894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acarbose Mitigates Age-Dependent Alterations in Erythrocyte Membrane Transporters During Aging in Rats.","authors":"Jitendra Kumar Arya, Raushan Kumar, Akanksha Singh, Parisha Srivastava, Arun Kumar Yadawa, Syed Ibrahim Rizvi","doi":"10.1089/rej.2023.0010","DOIUrl":"10.1089/rej.2023.0010","url":null,"abstract":"<p><p>Acarbose (ACA), a well-studied and effective inhibitor of α-amylase and α-glucosidase, is a postprandial-acting antidiabetic medicine. The membrane of the erythrocyte is an excellent tool for analyzing different physiological and biochemical activities since it experiences a range of metabolic alterations throughout aging. It is uncertain if ACA modulates erythrocyte membrane activities in an age-dependent manner. As a result, the current study was conducted to explore the influence of ACA on age-dependent deteriorated functions of transporters/exchangers, disrupted levels of various biomarkers such as lipid hydroperoxides (LHs), protein carbonyl (PCO), sialic acid (SA), total thiol (-SH), and erythrocyte membrane osmotic fragility. In addition to a concurrent increase in Na<sup>+</sup>/H<sup>+</sup> exchanger activity and concentration of LH, PCO, and osmotic fragility, we also detected a considerable decrease in membrane-linked activities of Ca<sup>2+</sup>-ATPase (PMCA) and Na<sup>+</sup>/K<sup>+</sup>-ATPase (NKA), as well as concentrations of SA and -SH in old-aged rats. The aging-induced impairment of the activities of membrane-bound ATPases and the changed levels of redox biomarkers were shown to be effectively restored by ACA treatment.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"26 4","pages":"139-146"},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10086519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a Novel Senolysis Approach Targeting the Senescent Fibroblast Marker HTR2A via Antibody-Dependent Cellular Cytotoxicity.","authors":"Kento Takaya, Toru Asou, Kazuo Kishi","doi":"10.1089/rej.2023.0020","DOIUrl":"https://doi.org/10.1089/rej.2023.0020","url":null,"abstract":"<p><p>Abnormal remodeling of collagen and extracellular matrix caused by the accumulation of senescent fibroblasts in the dermis is the most likely cause of skin aging. Therefore, the application of \"senolysis,\" in which only senescent cells are cleared from the body, has a potential in the development of antiaging treatments for skin. However, markers that label senescent fibroblasts only reflect the state of senescence, and it is important to develop markers as therapeutic targets to aid senolysis application. We investigated the potential of serotonin 2A receptor (HTR2A), which is involved in melanin production in response to ultraviolet light, as a senescent cell marker. The results showed that HTR2A is upregulated in aging dermal fibroblasts but is expressed at low levels in proliferating young cells. Flow cytometry demonstrated the presence of many HTR2A-positive cells in the aging cell population and few in the young cells. Furthermore, antibody-dependent cytotoxicity assays revealed that HTR2A preferentially sensitizes senescent fibroblasts and specifically damages only senescent cells by natural killer cells that recognize it. In conclusion, selective labeling of the novel senescent cell marker, HTR2A, could preferentially eliminate senescent cells and may contribute to the future development of novel skin senolysis approaches.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"26 4","pages":"147-158"},"PeriodicalIF":2.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10026730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}