{"title":"The role of Klotho and sirtuins in sleep-related cardiovascular diseases: a review study.","authors":"Farzaneh Rostamzadeh, Siyavash Joukar, Mahboobeh Yeganeh-Hajahmadi","doi":"10.1038/s41514-024-00165-1","DOIUrl":"10.1038/s41514-024-00165-1","url":null,"abstract":"<p><p>The prevalence of sleep disorders has been reported from 1.6% to 56.0%, worldwide. Sleep deprivation causes cardiovascular diseases (CVDs) including atherosclerosis, vascular aging, hypertension, heart dysfunction, reduced heart rate variability, and cardiac arrhythmia. Reduced tissue oxygen causes various CVDs by activating pro-inflammatory factors and increasing oxidative stress. Sleep disorders are more important and prevalent in older people and cause more severe cardiovascular complications. On the other hand, the reduction of Klotho level, an age-dependent protein whose expression decreases with age, is associated with age-related diseases. Sirtuins, class III histone deacetylases, also are among the essential factors in postponing cellular aging and increasing the lifespan of organisms, and they do this by regulating different pathways in the cell. Sirtuins and Klotho play an important role in the pathophysiology of CVDS and both have anti-oxidative stress and anti-inflammatory activity. Studies have shown that the levels of Klotho and sirtuins are altered in sleep disorders. In this article, alterations of Klotho and sirtuins in sleep disorders and in the development of sleep-related CVDs were reviewed and the possible signaling pathways were discussed. The inclusion criteria were studies with keywords of different types of sleep disorders and CVDs, klotho, SIRT1-7, and sirtuins in PubMed, Scopus, Embase، Science Direct، Web of Sciences and Google Scholar by the end of 2023. The studies revealed there is a bidirectional relationship between sleep disorders and the serum and tissue levels of Klotho and sirtuins and sleep related-CVDs.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"43"},"PeriodicalIF":4.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368099","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}
npj agingPub Date : 2024-09-30DOI: 10.1038/s41514-024-00169-x
Stuart G Snowden, Albert Koulman, Christian Gaser, Susanne E la Fleur, Tessa J Roseboom, Aniko Korosi, Susanne R de Rooij
{"title":"Prenatal exposure to undernutrition is associated with a specific lipid profile predicting future brain aging.","authors":"Stuart G Snowden, Albert Koulman, Christian Gaser, Susanne E la Fleur, Tessa J Roseboom, Aniko Korosi, Susanne R de Rooij","doi":"10.1038/s41514-024-00169-x","DOIUrl":"10.1038/s41514-024-00169-x","url":null,"abstract":"<p><p>Prenatal adversity affects cognitive and brain aging. Both lipid and leptin concentrations may be involved. We investigated if prenatal undernutrition is associated with a specific blood lipid profile and/or leptin concentrations, and if these relate to cognitive function and brain aging. 801 plasma samples of members of the Dutch famine birth cohort were assessed for lipidomics and leptin at age 58. Cognitive performance was measured with a Stroop task at 58, and MRI-based BrainAGE was derived in a subsample at 68. Out of 259 lipid signals, a signature of five identified individuals who were undernourished prenatally. These five lipids were not associated with cognitive performance, but three were predictive of BrainAGE. Leptin was not associated with prenatal famine exposure, Stroop performance, or BrainAGE. In conclusion, prenatal undernutrition was associated with an altered lipid profile predictive of BrainAGE 10 years later, demonstrating the potential of lipid profiles as early biomarkers for accelerated brain aging.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"42"},"PeriodicalIF":4.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335376","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}
npj agingPub Date : 2024-09-14DOI: 10.1038/s41514-024-00168-y
Emily A O'Sullivan, Ryan Wallis, Federica Mossa, Cleo L Bishop
{"title":"The paradox of senescent-marker positive cancer cells: challenges and opportunities.","authors":"Emily A O'Sullivan, Ryan Wallis, Federica Mossa, Cleo L Bishop","doi":"10.1038/s41514-024-00168-y","DOIUrl":"https://doi.org/10.1038/s41514-024-00168-y","url":null,"abstract":"<p><p>Senescence is an anti-tumour mechanism and hallmark of cancer. Loss or mutation of key senescence effectors, such as p16INK4A, are frequently observed in cancer. Intriguingly, some human tumours are both proliferative and senescent-marker positive (Sen-Mark+). Here, we explore this paradox, focusing on the prognostic consequences and the current challenges in classifying these cells. We discuss future strategies for Sen-Mark+ cell detection together with emerging opportunities to exploit senescence for cancer.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"41"},"PeriodicalIF":4.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11401916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305117","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":"Monitoring reaction time to digital device in the very-old to detect early cognitive decline.","authors":"Yukari Yamada, Tadahisa Okuda, Tomoe Uchida, Tatsuyoshi Ikenoue, Shingo Fukuma","doi":"10.1038/s41514-024-00167-z","DOIUrl":"10.1038/s41514-024-00167-z","url":null,"abstract":"<p><p>Early detection of cognitive decline is essential for timely intervention and effective management of age-related impairments. We monitored repetitive reaction times to a simple task on senior-friendly tablet computers among 72 functionally independent older adults, with a mean age of 82, ranging up to 100 years, within natural settings over two years. Functional principal component analyses revealed a consistent decrease in reaction time in line with their task experience among those without subjective cognitive decline. Conversely, individuals reporting subjective cognitive decline showed no consistent trend and exhibited wide variability over time. These distinctive reaction time trajectories in very old adults suggest the potential for monitoring as a non-invasive, convenient method for early detection of cognitive impairment.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"40"},"PeriodicalIF":4.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147242","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}
npj agingPub Date : 2024-08-17DOI: 10.1038/s41514-024-00166-0
Francisco Alejandro Lagunas-Rangel
{"title":"Aging insights from heterochronic parabiosis models.","authors":"Francisco Alejandro Lagunas-Rangel","doi":"10.1038/s41514-024-00166-0","DOIUrl":"10.1038/s41514-024-00166-0","url":null,"abstract":"<p><p>Heterochronic parabiosis consists of surgically connecting the circulatory systems of a young and an old animal. This technique serves as a model to study circulating factors that accelerate aging in young organisms exposed to old blood or induce rejuvenation in old organisms exposed to young blood. Despite the promising results, the exact cellular and molecular mechanisms remain unclear, so this study aims to explore and elucidate them in more detail.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"38"},"PeriodicalIF":4.1,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997150","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}
npj agingPub Date : 2024-08-08DOI: 10.1038/s41514-024-00163-3
Denis Sidorenko, Stefan Pushkov, Akhmed Sakip, Geoffrey Ho Duen Leung, Sarah Wing Yan Lok, Anatoly Urban, Diana Zagirova, Alexander Veviorskiy, Nina Tihonova, Aleksandr Kalashnikov, Ekaterina Kozlova, Vladimir Naumov, Frank W Pun, Alex Aliper, Feng Ren, Alex Zhavoronkov
{"title":"Precious2GPT: the combination of multiomics pretrained transformer and conditional diffusion for artificial multi-omics multi-species multi-tissue sample generation.","authors":"Denis Sidorenko, Stefan Pushkov, Akhmed Sakip, Geoffrey Ho Duen Leung, Sarah Wing Yan Lok, Anatoly Urban, Diana Zagirova, Alexander Veviorskiy, Nina Tihonova, Aleksandr Kalashnikov, Ekaterina Kozlova, Vladimir Naumov, Frank W Pun, Alex Aliper, Feng Ren, Alex Zhavoronkov","doi":"10.1038/s41514-024-00163-3","DOIUrl":"10.1038/s41514-024-00163-3","url":null,"abstract":"<p><p>Synthetic data generation in omics mimics real-world biological data, providing alternatives for training and evaluation of genomic analysis tools, controlling differential expression, and exploring data architecture. We previously developed Precious1GPT, a multimodal transformer trained on transcriptomic and methylation data, along with metadata, for predicting biological age and identifying dual-purpose therapeutic targets potentially implicated in aging and age-associated diseases. In this study, we introduce Precious2GPT, a multimodal architecture that integrates Conditional Diffusion (CDiffusion) and decoder-only Multi-omics Pretrained Transformer (MoPT) models trained on gene expression and DNA methylation data. Precious2GPT excels in synthetic data generation, outperforming Conditional Generative Adversarial Networks (CGANs), CDiffusion, and MoPT. We demonstrate that Precious2GPT is capable of generating representative synthetic data that captures tissue- and age-specific information from real transcriptomics and methylomics data. Notably, Precious2GPT surpasses other models in age prediction accuracy using the generated data, and it can generate data beyond 120 years of age. Furthermore, we showcase the potential of using this model in identifying gene signatures and potential therapeutic targets in a colorectal cancer case study.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"37"},"PeriodicalIF":4.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908750","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}
npj agingPub Date : 2024-08-05DOI: 10.1038/s41514-024-00162-4
Siting Ye, Shuo Ma, Shunming Liu, Yu Huang, Dantong Li, Min Li, Ting Su, Jing Luo, Chi Zhang, Danli Shi, Lianting Hu, Lei Zhang, Honghua Yu, Mingguang He, Xianwen Shang, Xueli Zhang
{"title":"Shared whole environmental etiology between Alzheimer's disease and age-related macular degeneration.","authors":"Siting Ye, Shuo Ma, Shunming Liu, Yu Huang, Dantong Li, Min Li, Ting Su, Jing Luo, Chi Zhang, Danli Shi, Lianting Hu, Lei Zhang, Honghua Yu, Mingguang He, Xianwen Shang, Xueli Zhang","doi":"10.1038/s41514-024-00162-4","DOIUrl":"10.1038/s41514-024-00162-4","url":null,"abstract":"<p><p>The comorbidity of Alzheimer's disease (AD) and age-related macular degeneration (AMD) has been established in clinical and genetic studies. There is growing interest in determining the shared environmental factors associated with both conditions. Recent advancements in record linkage techniques enable us to identify the contributing factors to AD and AMD from a wide range of variables. As such, we first constructed a knowledge graph based on the literature, which included all statistically significant risk factors for AD and AMD. An environment-wide association study (EWAS) was conducted to assess the contribution of various environmental factors to the comorbidity of AD and AMD based on the UK biobank. Based on the conditional Q-Q plots and Bayesian algorithm, several shared environmental factors were identified, which could be categorized into the domains of health condition, biological sample parameters, body index, and attendance availability. Finally, we generated a shared etiology landscape for AD and AMD by combining existing knowledge with our novel findings.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"36"},"PeriodicalIF":4.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895150","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}
npj agingPub Date : 2024-07-20DOI: 10.1038/s41514-024-00157-1
Jéssica D Hense, José V V Isola, Driele N Garcia, Larissa S Magalhães, Michal M Masternak, Michael B Stout, Augusto Schneider
{"title":"The role of cellular senescence in ovarian aging.","authors":"Jéssica D Hense, José V V Isola, Driele N Garcia, Larissa S Magalhães, Michal M Masternak, Michael B Stout, Augusto Schneider","doi":"10.1038/s41514-024-00157-1","DOIUrl":"10.1038/s41514-024-00157-1","url":null,"abstract":"<p><p>This review explores the relationship between ovarian aging and senescent cell accumulation, as well as the efficacy of senolytics to improve reproductive longevity. Reproductive longevity is determined by the age-associated decline in ovarian reserve, resulting in reduced fertility and eventually menopause. Cellular senescence is a state of permanent cell cycle arrest and resistance to apoptosis. Senescent cells accumulate in several tissues with advancing age, thereby promoting chronic inflammation and age-related diseases. Ovaries also appear to accumulate senescent cells with age, which might contribute to aging of the reproductive system and whole organism through SASP production. Importantly, senolytic drugs can eliminate senescent cells and may present a potential intervention to mitigate ovarian aging. Herein, we review the current literature related to the efficacy of senolytic drugs for extending the reproductive window in mice.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"35"},"PeriodicalIF":4.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736221","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}
npj agingPub Date : 2024-07-18DOI: 10.1038/s41514-024-00160-6
Sophie J Hopkin, Poppy Nathan, Laleh Pezhman, Jenefa Begum, Julia E Manning, Lauren M Quinn, G Ed Rainger, Helen M McGettrick, Asif J Iqbal, Myriam Chimen
{"title":"Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention.","authors":"Sophie J Hopkin, Poppy Nathan, Laleh Pezhman, Jenefa Begum, Julia E Manning, Lauren M Quinn, G Ed Rainger, Helen M McGettrick, Asif J Iqbal, Myriam Chimen","doi":"10.1038/s41514-024-00160-6","DOIUrl":"10.1038/s41514-024-00160-6","url":null,"abstract":"<p><p>Inflammageing leads to uncontrolled leukocyte trafficking in response to inflammatory insults. Here, we used a zymosan-induced peritonitis mouse model on inflammation to investigate the role of the PEPITEM pathway on leukocyte migration in ageing. We then analysed whether PEPITEM could modulate leukocyte migration in older adults. We observed a loss of functionality in the PEPITEM pathway, which normally controls leukocyte trafficking in response to inflammation, in older adults and aged mice and show that this can be rescued by supplementation with PEPITEM. Thus, leading to the exciting possibility that PEPITEM supplementation may represent a potential pre-habilitation geroprotective agent to rejuvenate immune functions.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"33"},"PeriodicalIF":4.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11258258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725423","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}
npj agingPub Date : 2024-07-15DOI: 10.1038/s41514-024-00159-z
Magnolia G Wang, Patrick Seale, David Furman
{"title":"The infrapatellar fat pad in inflammaging, knee joint health, and osteoarthritis.","authors":"Magnolia G Wang, Patrick Seale, David Furman","doi":"10.1038/s41514-024-00159-z","DOIUrl":"10.1038/s41514-024-00159-z","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common form of arthritis and accounts for nearly $140 billion in annual healthcare expenditures only in the United States. Obesity, aging, and joint injury are major risk factors for OA development and progression, but the mechanisms contributing to pathology remain unclear. Emerging evidence suggests that cellular dysregulation and inflammation in joint tissues, including intra-articular adipose tissue depots, may contribute to disease severity. In particular, the infrapatellar fat pad (IFP), located in the knee joint, which provides a protective cushion for joint loading, also secretes multiple endocrine factors and inflammatory cytokines (inflammaging) that can regulate joint physiology and disease. Correlates of cartilage degeneration and OA-associated disease severity include inflammation and fibrosis of IFP in model organisms and human studies. In this article, we discuss recent progress in understanding the roles and regulation of intra-articular fat tissue in regulating joint biology and OA.</p>","PeriodicalId":94160,"journal":{"name":"npj aging","volume":"10 1","pages":"34"},"PeriodicalIF":4.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622061","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}