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 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, rapamycin, 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.

Transcriptomic Effects of Healthspan-Promoting Dietary Interventions: Current Evidence and Future Directions

“…Indeed, there is a global increase in RE transcripts in model organisms and humans with aging (84), and some of these RE may be associated with certain hallmarks of aging, including inflammation, oxidative stress, and cellular senescence (85,86). Interestingly, CR is associated with a global reduction in RE transcripts in liver, which further supports the idea that global RE transcript dysregulation may be an important transcriptional hallmark of aging and healthy nutritional interventions (28). The influence of other nutritional interventions on RE with aging remains to be determined, but could be a promising area of future investigation.…”

“…Also, consistent with the observation that glucose homeostasis/insulin signaling are central players in the effects of CR on metabolism, CR changes the expression of key genes affecting energy/metabolismmodulating proteins and insulin secretion (largely reducing the expression of these genes) (6). In addition to glucose homeostasis, other pathways/genes contributing to DNA repair, fatty acid metabolism, and citric acid cycle/oxidative phosphorylation appear to be key transcriptomic mediators of the effects of CR in white adipose tissue and liver in pre-clinical models (27)(28)(29).…”

An eQTL-based Approach Reveals Candidate Regulators of LINE-1 RNA Levels in Lymphoblastoid Cells

“…Rapamycin, which acts through mTORC1, has been shown to alter the expression of L1 and other repeats 31,32 . Estrogens, which are involved in cholesterol and lipid metabolism, have been found to drive changes in repeat expression, and the receptors for both estrogens and androgens are believed to bind repeat DNA 32,33 .…”