Healthy Aging Interventions Reduce Repetitive Element Transcripts.

Transcripts from noncoding repetitive elements (REs) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and lifespan, and their role in healthy aging interventions has not been characterized. Here, we analyze REs in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, rapamycin, acarbose, 17-α-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to a high-fat diet, and we use RNA-seq to investigate the influence of aerobic exercise on RE transcripts with aging in humans. We find that (a) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and high-fat diet (an age-accelerating treatment) increase RE expression; and (b) reduced RE expression with healthy aging interventions is associated with biological/physiological processes mechanistically linked with aging. Our results suggest that RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.