Research Paper Volume 17, Issue 6 pp 1521—1543
Development of a novel transcriptomic measure of aging: Transcriptomic Mortality-risk Age (TraMA)
- 1 Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA
- 2 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
- 3 David Geffen School of Medicine, University of California, Los Angeles, CA 90089, USA
Received: February 6, 2025 Accepted: June 2, 2025 Published: June 13, 2025
https://doi.org/10.18632/aging.206272How to Cite
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.
Abbreviations
TraMA: Transcriptomic Measure of Aging; RNA: Ribonucleic acid; HRS: Health and Retirement Study; LLFS: Long Life Families Study; TWAS: Transcriptome-wide Association Study; VBS: Venous Blood Study; HR: Hazard Ratio; FDR: Benjamini-Hochberg False Discovery Rate; BMI: Body Mass Index; ADLs: Activities of Daily Living; IADLs: Instrumental Activities of Daily Living; TICS: Telephone Interview for Cognitive Status; GEO: Gene Expression Omnibus; FEV1: forced expiratory volume in one second; COPD: Chronic Obstructive Pulmonary Disease; MSCCR: Mount Sinai Crohn’s and Colitis Registry; IBD: inflammatory bowel disease; HBI: Harvey-Bradshaw index; SESCD: Simple Endoscopic Score for Crohn’s Disease; SOFA: Sequential Organ Failure Assessment; CpG: Cytosine-phosphate-guanine; DNAm: DNA methylation.