Phenome-Wide Multi-Omics Integration Uncovers Distinct Archetypes of Human Aging

Fuente: arXiv
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Main Authors: Li, Huifa, Tang, Feilong, Xue, Haochen, Li, Yulong, Zhuang, Xinlin, Zhang, Bin, Segal, Eran, Razzak, Imran
Format: Preprint
Published: 2025
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author Li, Huifa
Tang, Feilong
Xue, Haochen
Li, Yulong
Zhuang, Xinlin
Zhang, Bin
Segal, Eran
Razzak, Imran
author_facet Li, Huifa
Tang, Feilong
Xue, Haochen
Li, Yulong
Zhuang, Xinlin
Zhang, Bin
Segal, Eran
Razzak, Imran
contents Aging is a highly complex and heterogeneous process that progresses at different rates across individuals, making biological age (BA) a more accurate indicator of physiological decline than chronological age. While previous studies have built aging clocks using single-omics data, they often fail to capture the full molecular complexity of human aging. In this work, we leveraged the Human Phenotype Project, a large-scale cohort of 10,000 adults aged 40-70 years, with extensive longitudinal profiling that includes clinical, behavioral, environmental, and multi-omics datasets spanning transcriptomics, lipidomics, metabolomics, and the microbiome. By employing advanced machine learning frameworks capable of modeling nonlinear biological dynamics, we developed and rigorously validated a multi-omics aging clock that robustly predicts diverse health outcomes and future disease risk. Unsupervised clustering of the integrated molecular profiles from multi-omics uncovered distinct biological subtypes of aging, revealing striking heterogeneity in aging trajectories and pinpointing pathway-specific alterations associated with different aging patterns. These findings demonstrate the power of multi-omics integration to decode the molecular landscape of aging and lay the groundwork for personalized healthspan monitoring and precision strategies to prevent age-related diseases.
format Preprint
id arxiv_https___arxiv_org_abs_2510_12384
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Phenome-Wide Multi-Omics Integration Uncovers Distinct Archetypes of Human Aging
Li, Huifa
Tang, Feilong
Xue, Haochen
Li, Yulong
Zhuang, Xinlin
Zhang, Bin
Segal, Eran
Razzak, Imran
Genomics
Artificial Intelligence
Aging is a highly complex and heterogeneous process that progresses at different rates across individuals, making biological age (BA) a more accurate indicator of physiological decline than chronological age. While previous studies have built aging clocks using single-omics data, they often fail to capture the full molecular complexity of human aging. In this work, we leveraged the Human Phenotype Project, a large-scale cohort of 10,000 adults aged 40-70 years, with extensive longitudinal profiling that includes clinical, behavioral, environmental, and multi-omics datasets spanning transcriptomics, lipidomics, metabolomics, and the microbiome. By employing advanced machine learning frameworks capable of modeling nonlinear biological dynamics, we developed and rigorously validated a multi-omics aging clock that robustly predicts diverse health outcomes and future disease risk. Unsupervised clustering of the integrated molecular profiles from multi-omics uncovered distinct biological subtypes of aging, revealing striking heterogeneity in aging trajectories and pinpointing pathway-specific alterations associated with different aging patterns. These findings demonstrate the power of multi-omics integration to decode the molecular landscape of aging and lay the groundwork for personalized healthspan monitoring and precision strategies to prevent age-related diseases.
title Phenome-Wide Multi-Omics Integration Uncovers Distinct Archetypes of Human Aging
topic Genomics
Artificial Intelligence
url https://arxiv.org/abs/2510.12384