Mrna Granules and Proteostasis in Aging and Age-Related Diseases

Abstract

The maintenance of protein homeostasis (proteostasis) has emerged as a fundamental concept of the aging process and age-related diseases. Proteostasis is attained through highly complex and interconnecting processes that become compromised with aging. Likewise, stress caused by environmental insults or intrinsic factors often poses a threat to proteostasis, jeopardizing organismal fitness and survival. Cellular stress defense mechanisms involve specific mRNA granules that consist of various proteins and mRNAs, with diverse functions in localization, translation and turnover of mRNAs. These granules are also associated with basal post-transcriptional control of growth and a range of other physiological processes. Several findings also support their involvement in pathological protein aggregates that are formed in many age-related human diseases and lead to the disruption of proteostasis. Therefore, a cross-talk between mRNA granules and the protein quality control machinery is important to constantly ensure proper assembly, disassembly and function of these structures. This chapter summarizes the current knowledge on two major cytoplasmic mRNA granules, P-bodies and stress granules, And discusses the interconnection of these assemblies with the proteostasis network, focusing particularly on their critical role in the progression of aging and age-related diseases.