Bioinformatics and Genomic Networks Open access Peer reviewed

Nonlinear dynamics of multi-omics profiles during human aging

M Snyder, Xiaotao Shen, Chuchu Wang, Xin Zhou and 3 more

Nature Aging | Aug 14, 2024 | 326 citations

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Comprehensive multi-omics data is used to reveal nonlinear molecular profiles across chronological ages, highlighting two substantial variations observed around ages 40 and 60, which are linked to increased disease risks.

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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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M Snyder

last | Stanford Medicine | ORCID 0000-0003-0784-7987

Xiaotao Shen

first | Stanford University | ORCID 0000-0002-9608-9964

Chuchu Wang

middle | Howard Hughes Medical Institute | ORCID 0000-0003-2015-7331

Xin Zhou

middle | Stanford Medicine | ORCID 0000-0001-8089-4507

Wenyu Zhou

middle | Stanford University | ORCID 0000-0002-8447-8815

Daniel Hornburg

middle | Stanford University | ORCID 0000-0002-6618-7774

Si Wu

middle | Stanford University | ORCID 0000-0002-4526-2827

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BibTeX

@article{Snyder2024Nonlinear,
  title = {Nonlinear dynamics of multi-omics profiles during human aging},
  author = {M Snyder and Xiaotao Shen and Chuchu Wang and Xin Zhou and Wenyu Zhou and Daniel Hornburg and Si Wu},
  journal = {Nature Aging},
  year = {2024},
  doi = {10.1038/s43587-024-00692-2},
  url = {https://doi.org/10.1038/s43587-024-00692-2}
}

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