Research Paper|Volume 17, Issue 6|pp 1521—1543

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

Eric T. Klopack¹, Gokul Seshadri², Thalida Em Arpawong¹, Steve Cole³, Bharat Thyagarajan², Eileen M. Crimmins¹

¹Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA
²Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
³David Geffen School of Medicine, University of California, Los Angeles, CA 90089, USA

Received: February 6, 2025Accepted: June 2, 2025Published: June 13, 2025

https://doi.org/10.18632/aging.206272

Copyright: © 2025 Klopack et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.