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Aging is a complex process associated with nearly all diseases. Understanding the molecular changes underlying aging and identifying therapeutic targets for aging-related diseases are crucial for increasing healthspan. Although many studies have explored linear changes during aging, the prevalence of aging-related diseases and mortality risk accelerates after specific time points, indicating the importance of studying nonlinear molecular changes. In this study, we performed comprehensive multi-omics profiling on a longitudinal human cohort of 108 participants, aged between 25 years and 75 years. The participants resided in California, United States, and were tracked for a median period of 1.7 years, with a maximum follow-up duration of 6.8 years. The analysis revealed consistent nonlinear patterns in molecular markers of aging, with substantial dysregulation occurring at two major periods occurring at approximately 44 years and 60 years of chronological age. Distinct molecules and functional pathways associated with these periods were also identified, such as immune regulation and carbohydrate metabolism that shifted during the 60-year transition and cardiovascular disease, lipid and alcohol metabolism changes at the 40-year transition. Overall, this research demonstrates that functions and risks of aging-related diseases change nonlinearly across the human lifespan and provides insights into the molecular and biological pathways involved in these changes.
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http://dx.doi.org/10.1038/s43587-024-00692-2 | DOI Listing |
Lipids Health Dis
September 2025
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Background: The CRP-albumin-lymphocyte (CALLY) index has potential clinical value as a novel marker integrating inflammatory, nutritional and immune status in the development of colorectal polyps. This study examined whether gender factors influence the association between CALLY and colorectal polyps; in addition to elucidating whether metabolic pathways mediate this relationship.
Methods: This is a cross-sectional study including 5409 adult health screening participants who completed colonoscopy.
Exp Neurol
September 2025
Division of Pharmacology and Pharmacotherapy, Drug Research Programme, Faculty of Pharmacy, University of Helsinki, Finland; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland. Electronic address:
Traumatic brain injury (TBI) impacts up to 60 million people annually. Both severe TBIs and repeated mild TBIs (rmTBIs) can lead to persistent symptoms such as cognitive deficits, and even neurodegenerative diseases like chronic traumatic encephalopathy (CTE). To date, no therapies exist to mitigate the risk of CTE or other chronic symptoms post-TBI.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
September 2025
UMR 1098 RIGHT INSERM/Etablissement Français du Sang Bourgogne Franche-Comté/Université Marie et Louis Pasteur, 25000 Besançon, France.
Despite the clinical success of redirected T cells in the setting of cancer adoptive cell immunotherapy, patients may exhibit resistance to treatment, resulting in uncontrolled disease and relapses. This phenomenon partly relies on impaired -produced T cell metabolic fitness, including a decreased respiratory reserve, as well as a greater sensitivity to tumor-mediated metabolic stress. To improve the respiratory capacity of cultured T cells, we sought to target the nicotinamide adenine dinucleotide/sirtuine-1/reactive oxygen species (ROS) axis through supplementation of culture medium with resveratrol.
View Article and Find Full Text PDFJ Endocr Soc
October 2025
Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam University Medical Center, Location VUMC, 1081 HV Amsterdam, the Netherlands.
The gut microbiome is widely accepted to play a crucial role in human health and disease. These intestinal microbiota are not only involved in gastrointestinal physiology, but they also contribute to essential immune modulation and metabolic homeostasis. Growing evidence suggests that alterations in the gut microbiota composition are linked to various metabolic disorders, including obesity and age-related diseases.
View Article and Find Full Text PDFSci Bull (Beijing)
August 2025
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institute of Advanced Clinical Medicine, Peking University, Beijing 100191, China; Beijing Advanced Center of Cellular Homeostasis and Aging-Related Diseases, Institute of Advanced Clinical Medicine, Peking Universit