npj aging最新文献_第2页

Biological aging increases risk of postoperative morbidity and mortality: an international, multi-cohort study. 生物老化增加术后发病率和死亡率的风险：一项国际多队列研究。

IF 13

npj aging Pub Date : 2026-07-04 DOI: 10.1038/s41514-026-00441-2

Joseph R Scarpa, M Cary Reid, Olivier Elemento, Jan Krumsiek

{"title":"Biological aging increases risk of postoperative morbidity and mortality: an international, multi-cohort study.","authors":"Joseph R Scarpa, M Cary Reid, Olivier Elemento, Jan Krumsiek","doi":"10.1038/s41514-026-00441-2","DOIUrl":"10.1038/s41514-026-00441-2","url":null,"abstract":"Biological age often diverges from chronological age, yet its independent impact on surgical outcomes remains poorly defined. We evaluated PhenoAge, a validated biological age metric, in an international multi-cohort study comprising over 430,000 surgical patients across the UK, USA, and South Korea. In the UK Biobank (N = 291,845), PhenoAge was a robust, independent predictor of 1-year mortality (OR 1.043; p < 0.001), major adverse cardiovascular events (OR 1.041; p < 0.001), and 30-day readmission (OR 1.02; p < 0.001), even after adjusting for chronological age, Fried Frailty Index, Charlson comorbidity score, American Society of Anesthesiologists (ASA) physical status, surgical complexity, and other common surgical risk factors. \"Fast Agers\" faced a 49% higher risk of mortality than \"Normal Agers\". The main findings were replicated across three independent international cohorts (MOVER OR 1.03; Weill Cornell OR 1.036; INSPIRE OR: 1.05; all p < 0.001), and validated prospectively at a large academic medical center, where PhenoAge predicted acute 3-day complications (OR 1.20; p = 0.015). As a scalable tool leveraging routine laboratory data, PhenoAge facilitates precision gerisurgery by identifying high-risk individuals for prehabilitation and biologically resilient candidates for complex procedures regardless of chronological age.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Telomere integrity, epigenetic aging, and genetic burden shape biological aging trajectories in idiopathic pulmonary fibrosis. 端粒完整性、表观遗传老化和遗传负担形成特发性肺纤维化的生物学老化轨迹。

IF 13

npj aging Pub Date : 2026-07-03 DOI: 10.1038/s41514-026-00434-1

Manuela Campisi, Luana Cannella, Filippo Liviero, Federico Tamiazzo, Elisabetta Balestro, Paolo Spagnolo, Sofia Pavanello

{"title":"Telomere integrity, epigenetic aging, and genetic burden shape biological aging trajectories in idiopathic pulmonary fibrosis.","authors":"Manuela Campisi, Luana Cannella, Filippo Liviero, Federico Tamiazzo, Elisabetta Balestro, Paolo Spagnolo, Sofia Pavanello","doi":"10.1038/s41514-026-00434-1","DOIUrl":"https://doi.org/10.1038/s41514-026-00434-1","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a paradigmatic aging-related lung disorder. In this retrospective cohort study, we evaluated 101 treatment-naïve patients at diagnosis (T0) and a subgroup (n = 31) after one year of antifibrotic therapy (T1). Analyses included leukocyte telomere length (LTL), DNA methylation age [DNAmAge assessed by Horvath, Levine (PhenoAge), Skin & Blood, Hannum, BLUP, Elastic Net (EN), and a 5-CpG panel], age acceleration (AgeAcc), and genetic susceptibility. At T1, LTL was independently predicted by baseline LTL (p = 0.0004) and treatment duration (p = 0.0056). Longitudinally, ΔLTL increased in nintedanib- versus pirfenidone-treated patients (p = 0.0402) and with treatment duration (p = 0.0233). DNAmAge modestly increased with chronological aging across all clocks, while AgeAcc remained stable, decreasing at follow-up (p = 0.0435) and higher in males (p = 0.0204). Genetic analyses on 17 IPF-associated SNPs confirmed enrichment of established risk variants, including MUC5B and DPP9, and identified an association between higher genetic burden and lower forced vital capacity (p = 0.0136). Extending this approach, genome-wide imputation enabled polygenic risk score (PRS) analysis, revealing significant case-control differences and discrimination (AUC up to 0.79), supporting a measurable polygenic contribution to disease susceptibility. These findings highlight the added value of integrating telomeric, epigenetic, and genome-wide genetic burden-captured through PRS-for improved risk stratification in IPF.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The cancer Alzheimer's disease paradox. 癌症阿尔茨海默病悖论。

IF 13

npj aging Pub Date : 2026-07-02 DOI: 10.1038/s41514-026-00442-1

L Rebekah Feng

引用次数: 0

The evolution of aging research: from theories to epigenetic reprogramming. 衰老研究的演变：从理论到表观遗传重编程。

IF 13

npj aging Pub Date : 2026-06-29 DOI: 10.1038/s41514-026-00437-y

Elena-Cristina Găitănaru, Andreea Angelica Stroe, Sergiu Emil Georgescu, Roua Gabriela Popescu, George Cătălin Marinescu

引用次数: 0

Motor unit behavior adaptations across lifespan: sex differences in young, middle-aged and old adults. 运动单元行为的终生适应：青年、中年和老年人的性别差异。

IF 13

npj aging Pub Date : 2026-06-29 DOI: 10.1038/s41514-026-00427-0

Marco Carbonaro, Marta Boccardo, Clarissa M Brusco, Andrea M Pilotto, Rebecca Re, Fulvio Lauretani, Simone Porcelli, Martino V Franchi, Alberto Botter

{"title":"Motor unit behavior adaptations across lifespan: sex differences in young, middle-aged and old adults.","authors":"Marco Carbonaro, Marta Boccardo, Clarissa M Brusco, Andrea M Pilotto, Rebecca Re, Fulvio Lauretani, Simone Porcelli, Martino V Franchi, Alberto Botter","doi":"10.1038/s41514-026-00427-0","DOIUrl":"https://doi.org/10.1038/s41514-026-00427-0","url":null,"abstract":"Aging is associated with neuromuscular decline, but how sex modulates motor unit adaptations across adulthood remains unclear. This study examined age- and sex-related differences in motor unit firing behavior in young (YG), middle-aged (MA), and older (OLD) adults by integrating high-density surface EMG decomposition with assessments of muscle morphology and daily physical activity. Linear mixed-effects models revealed significant effects of age and sex on mean firing rate: females showed higher rates than males at 30% maximal voluntary contraction (MVC) in YG and MA groups, but not in OLD, and no sex differences were observed at 50% MVC. Firing-rate variability was consistently higher in females. During force-increasing contractions, OLD adults showed reduced motor unit discharge modulation; in early-recruited units, reductions were significant in OLD females relative to both YG and MA females, while males showed reductions across both early- and late-recruited units. Males exhibited greater muscle thickness, cross-sectional area, and maximal torque, and daily physical activity was lower in OLD participants. These findings indicate that neuromuscular aging is associated with reduced discharge-rate modulation and a convergence of motor unit behavior between sexes in older age. Physical activity may contribute, underscoring the importance of sex-sensitive strategies to preserve neuromuscular function.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endothelial extracellular vesicles preserve vascular smooth muscle cell identity but do not reverse endothelial senescence. 内皮细胞外囊泡保留血管平滑肌细胞的特性，但不能逆转内皮细胞衰老。

IF 13

npj aging Pub Date : 2026-06-26 DOI: 10.1038/s41514-026-00438-x

Úrsula Zúñiga-Cuevas, Vania Otárola-Urrutia, Leslye Venegas-Zamora, Magda C Díaz-Vesga, Camila López-Torres, Javiera Favi-Coloma, Constanza Rimassa-Taré, Ximena Calle-Chalco, Andrés Ramírez-Reyes, Alejandra Hernández, Danica Jiménez-Gallegos, Sebastián Urquiza-Zurich, Mayarling F Troncoso, Ignacio Norambuena-Soto, Mario Chiong, Valentina Parra, Sergio Lavandero, Jaime A Riquelme

引用次数: 0

Association between socioeconomic position and transitions to multimorbidity involving major chronic diseases in Northwest Italy. 社会经济地位与意大利西北部涉及主要慢性疾病的多病过渡之间的关系。

IF 13

npj aging Pub Date : 2026-06-26 DOI: 10.1038/s41514-026-00435-0

Francesca Mori, Luca Manfredi, Roberto Gnavi, Elisa Ferracin, Roberta Picariello, Lorenzo Milani, Federica Buscema, Maria Teresa Giraudo, Fulvio Ricceri

{"title":"Association between socioeconomic position and transitions to multimorbidity involving major chronic diseases in Northwest Italy.","authors":"Francesca Mori, Luca Manfredi, Roberto Gnavi, Elisa Ferracin, Roberta Picariello, Lorenzo Milani, Federica Buscema, Maria Teresa Giraudo, Fulvio Ricceri","doi":"10.1038/s41514-026-00435-0","DOIUrl":"https://doi.org/10.1038/s41514-026-00435-0","url":null,"abstract":"Multimorbidity, the co-occurrence of multiple chronic conditions in individuals, complicates clinical management, increases healthcare use, and reduces life quality. This study investigates the association between socioeconomic position and multimorbidity, restricted to co-occurrence of two or more conditions among type 2 diabetes, cardiovascular diseases, selected cancers as a single category, chronic obstructive pulmonary disease, and depression, in a population-based cohort in Piedmont, Italy. A multimorbidity registry was built from 2013 to 2019, and diseases were identified through healthcare databases. Multistate models estimated the association between multimorbidity and socioeconomic position, stratifying by sex. Among 1,534,975 individuals, multimorbidity incidence was 1.31 (95% CI: 1.29-1.33) per 100,000 person-days. Lower SEP was associated with higher risk in almost all transitions to T2D and to CVD. In women, borderline significant associations were found from cancer to depression and from COPD to depression, comparing the lowest to the highest SEP. In men, significant associations were found for transitions to COPD as well as from COPD to cancer and from depression to cancer. Lower SEP was consistently associated with higher risks of single diseases and multimorbidity, with some sex-specific patterns. These findings highlight cumulative disadvantage and the need for policies targeting health inequalities in aging populations.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative organ-wide analysis of age-related N-glycan alterations in mice reveals a link to lysosomal glycosidases. 对小鼠年龄相关的n-聚糖改变的比较全器官分析揭示了与溶酶体糖苷酶的联系。

IF 13

npj aging Pub Date : 2026-06-26 DOI: 10.1038/s41514-026-00436-z

Keiko Akasaka-Manya, Hisatoshi Hanamatsu, Ikuko Yokota, Kazue Okada, Akihiro Fujita, Jun-Ichi Furukawa, Tamao Endo, Hiroshi Manya

{"title":"Comparative organ-wide analysis of age-related N-glycan alterations in mice reveals a link to lysosomal glycosidases.","authors":"Keiko Akasaka-Manya, Hisatoshi Hanamatsu, Ikuko Yokota, Kazue Okada, Akihiro Fujita, Jun-Ichi Furukawa, Tamao Endo, Hiroshi Manya","doi":"10.1038/s41514-026-00436-z","DOIUrl":"https://doi.org/10.1038/s41514-026-00436-z","url":null,"abstract":"Glycosylation is an important post-translational modification, and glycan alterations reflect physiological and pathological states. However, whether common age-associated glycan changes occur across organs remains unclear. Here, we analyzed protein-bound N-glycans in serum, brain, lung, heart, liver, skeletal muscle, and kidney to identify aging-related alterations shared across tissues. Although glycan profiles were strongly organ-specific, age-dependent changes were observed in each organ. The proportion of paucimannose glycans increased in multiple organs and showed a significant positive correlation with age. The lysosomal glycosidases Hexa/Hexb, which are potentially involved in paucimannose glycan generation, were upregulated in the lung during aging. In cultured cells, elevated expression of these enzymes and increased paucimannose glycans were observed in senescent cells. These findings suggest that paucimannose glycans are closely associated with aging, although a causal role of HEXA/HEXB upregulation in their formation was not directly tested; they may also serve as indicators of cellular and organ aging.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Somatic mutations impose an entropic upper bound on human lifespan. 体细胞突变对人类寿命施加了一个熵上限。

IF 13

npj aging Pub Date : 2026-06-25 DOI: 10.1038/s41514-026-00421-6

Evgeniy Efimov, Vlad Fedotov, Leonid Malaev, Ekaterina E Khrameeva, Dmitrii Kriukov

{"title":"Somatic mutations impose an entropic upper bound on human lifespan.","authors":"Evgeniy Efimov, Vlad Fedotov, Leonid Malaev, Ekaterina E Khrameeva, Dmitrii Kriukov","doi":"10.1038/s41514-026-00421-6","DOIUrl":"10.1038/s41514-026-00421-6","url":null,"abstract":"Somatic mutations accumulate with age and can cause cell death, but their quantitative contribution to limiting human lifespan remains unclear. We developed an incremental modeling framework that progressively incorporates factors contributing to aging into a model of population survival dynamics, which we used to estimate lifespan limits if all aging hallmarks were eliminated except somatic mutations. Our analysis reveals fundamental asymmetry across organs: post-mitotic cells such as neurons and cardiomyocytes act as critical longevity bottlenecks, with somatic mutations reducing median lifespan from a theoretical non-aging baseline of 1759 years to 156 years. In contrast, proliferating tissues like liver maintain functionality for thousands of years through cellular replacement, effectively neutralizing mutation-driven decline. Multi-organ integration predicts median lifespans of 146-194 years-approximately twice current human longevity. This substantial yet incomplete reduction indicates that somatic mutations significantly drive aging but cannot alone account for observed mortality, implying comparable contributions from other hallmarks.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335324","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}

引用次数: 0

Intermittent hypoxia induces reversible epigenetic age acceleration in old mice. 间歇性缺氧诱导老年小鼠可逆性表观遗传年龄加速。

IF 13

npj aging Pub Date : 2026-06-23 DOI: 10.1038/s41514-026-00425-2

Stefano Donega, Ake T Lu, Amin Haghani, Markus Horvath, Qi Yan, Mirko Baranzini, Maxine Thea Escote, Martina Rossi, Rolando J Hernandez, Ross A McDevitt, Kenneth W Fishbein, Steve Horvath, Luigi Ferrucci

{"title":"Intermittent hypoxia induces reversible epigenetic age acceleration in old mice.","authors":"Stefano Donega, Ake T Lu, Amin Haghani, Markus Horvath, Qi Yan, Mirko Baranzini, Maxine Thea Escote, Martina Rossi, Rolando J Hernandez, Ross A McDevitt, Kenneth W Fishbein, Steve Horvath, Luigi Ferrucci","doi":"10.1038/s41514-026-00425-2","DOIUrl":"https://doi.org/10.1038/s41514-026-00425-2","url":null,"abstract":"Epigenetic mechanisms are considered adaptive regulators of gene expression, yet mechanisms driving aging-associated DNA methylation remain unclear. Prior work hinted that epigenetic aging might reflect a response to oxygen availability, with age‑differential methylation in immune cells enriched near binding sites for hypoxia‑responsive factors ARNT and REST. To test this hypothesis, we exposed adult (11 months) and old (23 months) mice to 1 month of intermittent hypoxia (IH) followed by normoxic recovery. IH induced epigenetic age acceleration in lungs, spleen, and heart in old mice only. This acceleration reversed upon return to normoxia. Reversible shifts were enriched at bivalent domains and PRC2 targets, indicating oxygen-sensitive chromatin remodeling. Human translational validation in young adults at high altitude (5260 m) confirmed rapid, conserved epigenetic aging. Our findings establish oxygen availability as a primary, conserved modulator of epigenetic aging across tissues and species, showing that oxygen fluctuations are a potent, reversible driver of epigenetic aging.","PeriodicalId":94160,"journal":{"name":"npj aging","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0