Modulation of the repetitive element transcriptome by healthy aging interventions

Growing evidence indicates that non‐coding repetitive elements (RE) may play an important role in aging. For example, recent studies have shown that age‐related RE transcript accumulation may cause pro‐inflammatory signaling and be detrimental to cardiometabolic health. However, RE are often ignored in transcriptome studies on aging. Moreover, their role in well‐known healthy aging interventions has not been comprehensively characterized, and the link between RE transcript accumulation and lifespan is unknown. To investigate this, we have analyzed RE transcript expression in multiple RNA‐seq datasets on aging, and in transcriptome data on mice subjected to several of the most robust and well‐studied lifespan increasing interventions, including: calorie restriction (CR), acarbose, mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">Rapamycin(definition), Protandim, and 17‐□ estradiol. We find that aging is associated with a general accumulation of RE transcripts in multiple tissues, but that CR significantly reduces the expression of >60% of RE transcripts in the liver and brain (p<0.05 vs. controls). We also observe that RE transcript levels are modulated significantly by Rapamycin, acarbose, and Protandim. Overlap analyses indicate that certain RE transcripts are affected by multiple interventions, suggesting that these RE may play a particularly important role in aging and healthy aging interventions, and we are investigating correlations among these RE transcripts and transcriptome signatures of adverse aging processes including inflammation. Collectively, our results suggest that the accumulation of RE transcripts may play an important role in aging and represent a novel target for increasing lifespan. Support or Funding Information R21: AG060302