Lin28 and let-7 in the Metabolic Physiology of Aging

Abstract

The Lin28/let-7 molecular switch has emerged as a central regulator of growth signaling pathways and metabolic enzymes. Initially discovered to regulate developmental timing in the nematode, the Lin28/let-7 pathway of RNA regulation has gained prominence for its role in mammalian stem cells, cancer cells, tissue development, and aging. By regulating RNAs, the pathway coordinates cellular growth and cellular metabolism to influence metabolic physiology. Here, we review this regulatory mechanism and its impact on cancers, which reactivate Lin28, cardiovascular diseases, which implicate let-7, human genome-wide association studies (GWAS) of growth, and metabolic diseases, which implicate the Lin28/let-7 pathway. We also highlight questions relating to Barker's Hypothesis and the potential actions of the Lin28/let-7 pathway on programming long-lasting epigenetic effects.

Keywords: Lin28; cancer; cardiomyopathy; diabetes; let-7; metabolism.