Nature Medicine最新文献

{"title":"How to measure biological aging in humans","authors":"Luigi Ferrucci, Nir Barzilai, Daniel W. Belsky, Vadim N. Gladyshev","doi":"10.1038/s41591-025-03550-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03550-9","url":null,"abstract":"<p>We were intrigued by the article by M. Arfan Ikram regarding the purported ‘misuse’ of biological aging, recently published in <i>Nature Medicine</i>¹. We are grateful to the author for raising this important issue but would like to offer a counterpoint to enrich the scientific dialogue on this topic.</p><p>When Peto and Doll stated “There is no such thing as aging”², they could not have anticipated the remarkable advancements in the understanding of the biology of aging over the subsequent two decades, including the development of various types of aging biomarkers. Although we concur that aging does not equal changes over time (but involves the accumulation of negative consequences of life, such as damage to macromolecules and organelles), dismissing the idea of any biomarkers based on calendar age as an approximate measure of aging seems counterproductive. Calendar age is deeply rooted in human life, science and society; it is reasonable to think that the accumulation of damage over time must come with consequences for health. It is also important to clarify how aging, biological age and disease are defined, because there is wide difference of opinion on these terms and concepts.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"54 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial cell-related genetic variants identify LDL cholesterol-sensitive individuals who derive greater benefit from aggressive lipid lowering","authors":"Nicholas A. Marston,&nbsp;Frederick K. Kamanu,&nbsp;Giorgio E. M. Melloni,&nbsp;Gavin Schnitzler,&nbsp;Aaron Hakim,&nbsp;Rosa X. Ma,&nbsp;Helen Kang,&nbsp;Daniel I. Chasman,&nbsp;Robert P. Giugliano,&nbsp;Patrick T. Ellinor,&nbsp;Paul M. Ridker,&nbsp;Jesse M. Engreitz,&nbsp;Marc S. Sabatine,&nbsp;Christian T. Ruff,&nbsp;Rajat M. Gupta","doi":"10.1038/s41591-025-03533-w","DOIUrl":"10.1038/s41591-025-03533-w","url":null,"abstract":"The role of endothelial cell (EC) dysfunction in contributing to an individual’s susceptibility to coronary atherosclerosis and how low-density lipoprotein cholesterol (LDL-C) concentrations might modify this relationship have not been previously studied. Here, from an examination of genome-wide significant single nucleotide polymorphisms associated with coronary artery disease (CAD), we identified variants with effects on EC function and constructed a 35 single nucleotide polymorphism polygenic risk score comprising these EC-specific variants (EC PRS). The association of the EC PRS with the risk of incident cardiovascular disease was tested in 3 cohorts: a primary prevention population in the UK Biobank (UKBB; n = 348,967); a primary prevention cohort from a trial that tested a statin (JUPITER, n = 8,749); and a secondary prevention cohort that tested a PCSK9 inhibitor (FOURIER, n = 14,298). In the UKBB, the EC PRS was independently associated with the risk of incident CAD (adjusted hazard ratio (aHR) per 1 s.d. of 1.24 (95% CI 1.21–1.26), P &lt; 2 × 10−16). Moreover, LDL-C concentration significantly modified this risk: the aHR per 1 s.d. was 1.26 (1.22–1.30) when LDL-C was 150 mg dl−1 but 1.00 (0.85–1.16) when LDL-C was 50 mg dl−1 (Pinteraction = 0.004). The clinical benefit of LDL-C lowering was significantly greater in individuals with a high EC PRS than in individuals with low or intermediate EC PRS, with relative risk reductions of 68% (HR 0.32 (0.18–0.59)) versus 29% (HR 0.71 (0.52–0.95)) in the primary prevention cohort (Pinteraction = 0.02) and 33% (HR 0.67 (0.53–0.83)) versus 8% (HR 0.92 (0.82–1.03)) in the secondary prevention cohort (Pinteraction = 0.01). We conclude that EC PRS quantifies an independent axis of CAD risk that is not currently captured in medical practice and identifies individuals who are more sensitive to the atherogenic effects of LDL-C and who would potentially derive substantially greater benefit from aggressive LDL-C lowering. From an analysis of participants in lipid-lowering trials for primary and secondary prevention of coronary artery disease, a polygenic risk score comprising 35 single nucleotide variants with predicted effects on endothelial cell function identified patients who benefited most from aggressive lipid-lowering therapy.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 3","pages":"963-969"},"PeriodicalIF":58.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI tool reads immune signatures to detect disease","authors":"","doi":"10.1038/d41591-025-00016-w","DOIUrl":"https://doi.org/10.1038/d41591-025-00016-w","url":null,"abstract":"A machine learning framework — trained on B cell and T cell receptor sequences from thousands of people — can detect a range of infectious and autoimmune diseases.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"6 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bispecific antibody delivers new treatment for NRG1 fusion–positive cancers","authors":"","doi":"10.1038/d41591-025-00015-x","DOIUrl":"https://doi.org/10.1038/d41591-025-00015-x","url":null,"abstract":"In a phase 2 registrational trial, zenocutuzumab showed durable anti-tumor activity across a variety of NRG1 fusion-positive cancer types, providing a new treatment for patients with few alternative options.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"8 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic editing of PCSK9 for a durable reduction in cholesterol","authors":"","doi":"10.1038/s41591-025-03583-0","DOIUrl":"https://doi.org/10.1038/s41591-025-03583-0","url":null,"abstract":"A sustained decrease in low-density lipoprotein cholesterol (LDL-C) is key to reducing the risk of atherosclerotic cardiovascular disease; however, achieving this goal can be hampered by low adherence to standard of care and the sub-maximal efficacy of currently available long-acting therapeutics. We developed an epigenetic editor that targets PCSK9 and robustly and durably decreases LDL-C.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"15 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoplastics in the human brain and their change in abundance over time","authors":"","doi":"10.1038/s41591-025-03571-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03571-4","url":null,"abstract":"Nanoplastics were identified in human brain samples from cadavers. Concentrations were higher in the brain than in the liver or kidneys, and appeared to increase over time between 2016 and 2024. Visualization of the plastics using a variety of approaches provided insights into the anatomical distribution and physical characteristics of nanoplastics.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global patterns and trends in breast cancer incidence and mortality across 185 countries","authors":"Joanne Kim, Andrew Harper, Valerie McCormack, Hyuna Sung, Nehmat Houssami, Eileen Morgan, Miriam Mutebi, Gail Garvey, Isabelle Soerjomataram, Miranda M. Fidler-Benaoudia","doi":"10.1038/s41591-025-03502-3","DOIUrl":"https://doi.org/10.1038/s41591-025-03502-3","url":null,"abstract":"<p>Updates of current and projected estimates of the burden are critical to monitoring the success of ongoing efforts in breast cancer control, such as the World Health Organization Global Breast Cancer Initiative, which aims to reduce breast cancer mortality by 2.5% per year. We investigated the current (2022) and future (2050) global burden of female breast cancer overall, and by age group, in 185 countries using the GLOBOCAN database, and 10-year trends in incidence and mortality rates in 50 and 46 countries, respectively, using the Cancer Incidence in Five Continents plus and World Health Organization mortality databases. Globally, 2.3 million new cases and 670,000 deaths from female breast cancer occurred in 2022. Annual rates increased by 1–5% in half of examined countries. Mortality rates decreased in 29 countries with very high Human Development Index (HDI), and seven countries (for example, Belgium and Denmark) are meeting the Global Breast Cancer Initiative goal of at least a 2.5% decrease each year. By 2050, new cases and deaths will have increased by 38% and 68%, respectively, disproportionately impacting low-HDI countries. High-quality cancer and vital status data, and continued progress in early diagnosis and access to treatment, are needed in countries with low and medium HDI to address inequities and monitor cancer control goals.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"15 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five ways to enhance the diversity and quality of health data","authors":"Paola Quattroni, Ash Routen, Joe Alderman, Claire Argent, Samuel Cushworth, Hajira Dambha-Miller, Rose Drummond, Alastair Denniston, Pushali Ganguli, Nicola Hamilton, Uwaye Ideh, Sara Khalid, Aden Kwok, Elinor Laws, Xiaoxuan Liu, Vahe Nafilyan, Jo Palmer, Marta Pineda-Moncusi, Alexia Sampri, Holly Tibble, Fatemeh Torabi, Jonathan Valabhji, Diana Withrow, Claire Welsh, Angela M. Wood, Ashley Akbari, Kamlesh Khunti","doi":"10.1038/s41591-025-03545-6","DOIUrl":"https://doi.org/10.1038/s41591-025-03545-6","url":null,"abstract":"The UK Health Data Research Alliance presents five recommendations for improving data collection for inclusive health research.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"18 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steps to prevent and respond to an H5N1 epidemic in the USA","authors":"Ranu S. Dhillon, Abraar Karan, Robert F. Garry, Devabhaktuni Srikrishna","doi":"10.1038/s41591-025-03527-8","DOIUrl":"https://doi.org/10.1038/s41591-025-03527-8","url":null,"abstract":"Steps should be taken now to prevent an epidemic of H5N1 in humans and prepare for an outbreak should it occur.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"27 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual immunotherapy benefits certain patients with metastatic colorectal cancer","authors":"","doi":"10.1038/d41591-025-00014-y","DOIUrl":"https://doi.org/10.1038/d41591-025-00014-y","url":null,"abstract":"The phase 3 CheckMate 8HW trial shows superior outcomes with nivolumab plus ipilimumab (compared with nivolumab monotherapy) in patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"3 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}