Healthy aging interventions reduce non-coding repetitive element transcripts

ABSTRACT Transcripts from non-coding repetitive elements (RE) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan(definition) and lifespan, and their role in healthy aging interventions has not been characterized. Here, we analyze RE in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition), acarbose, 17-α-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to 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: 1) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and age-accelerating treatments increase RE expression; and 2) reduced RE expression with healthy aging interventions is associated with biological/physiological processes mechanistically linked with aging. Thus, RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.