Development of a novel transcriptomic measure of aging: Transcriptomic Mortality-risk Age (TraMA).

Journal: Aging
Published Date: Jun 13, 2025

Abstract

Increasingly, research suggests that aging is a coordinated multi-system decline in functioning that occurs at multiple biological levels. We developed and validated a transcriptomic (RNA-based) aging measure we call Transcriptomic Mortality-risk Age (TraMA) using RNA-seq data from the 2016 Health and Retirement Study using elastic net Cox regression analyses to predict 4-year mortality hazard. In a holdout test sample, TraMA was associated with earlier mortality, more chronic conditions, poorer cognitive functioning, and more limitations in activities of daily living. TraMA was also externally validated in the Long Life Family Study and several publicly available datasets. Results suggest that TraMA is a robust, portable RNAseq-based aging measure that is comparable, but independent from past biological aging measures (e.g., GrimAge). TraMA is likely to be of particular value to researchers interested in understanding the biological processes underlying health and aging, and for social, psychological, epidemiological, and demographic studies of health and aging.

Authors

  • Eric T Klopack
    Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
  • Gokul Seshadri
    Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Thalida Em Arpawong
    Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
  • Steve Cole
    David Geffen School of Medicine, University of California, Los Angeles, CA 90089, USA.
  • Bharat Thyagarajan
    Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Eileen M Crimmins
    Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

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