The Role of MicroRNAs in Proteostasis Decline and Protein Aggregation during Brain and Skeletal Muscle Aging

Abstract

Aging can be defined as the progressive deterioration of cellular, tissue, and organismal function over time. Alterations in protein homeostasis, also known as proteostasis, are a hallmark of aging that lead to proteome imbalances and protein aggregation, phenomena that also occur in age-related diseases. Among the various proteostasis regulators, microRNAs (miRNAs) have been reported to play important roles in the post-transcriptional control of genes involved in maintaining proteostasis during the lifespan in several organismal tissues. In this review, we consolidate recently published reports that demonstrate how miRNAs regulate fundamental proteostasis-related processes relevant to tissue aging, with emphasis on the two most studied tissues, brain tissue and skeletal muscle. We also explore an emerging perspective on the role of miRNA regulatory networks in age-related protein aggregation, a known hallmark of aging and age-related diseases, to elucidate potential miRNA candidates for anti-aging diagnostic and therapeutic targets.

Regulatory RNAs in immunosenescence

“…The role of MiRNAs in the proteostasis regulation such as translation, folding, and degradation has been reported recently. 72 A previous study found that miR-425 interacts with heat shock protein B8 (HSPB8) and promotes tau phosphorylation in HEK293/tau cells which is related to senescence-associated Alzheimer's disease. 73 Furthermore, organelle stress responses like ER stress contribute to the maintenance of proteostasis.…”

Fiber-Type Shifting in Sarcopenia of Old Age: Proteomic Profiling of the Contractile Apparatus of Skeletal Muscles

“…Recent publications have critically examined the diverse and multi-factorial aspects of aging and sarcopenia, including senescence-related changes linked to abnormal metabolic pathways [364], mitochondrial dysfunctions [365][366][367][368][369][370][371], the role of reactive oxygen species and disrupted redox signaling [372][373][374][375], abnormal calcium handling [376], functional changes in neuromuscular transmission [377], altered myokine and myomitokine signaling [369,378], the role of miRNAs in the decline of proteostasis [379,380], anabolic resistance and impaired muscle protein metabolism [381][382][383], adipocyte crosstalk in aged skeletal muscle and sarcopenic obesity [384,385], immune system alterations, chronic inflammation and immune-metabolic dysfunction associated with oxidative stress [33,366,[386][387][388], the role of telomere length during aged fiber regeneration [389], the interplay between sarcopenia, frailty and cognitive impairments in the elderly [390], cardio-sarcopenia syndrome [337] and the influence of nutrition on the aging phenotype [391]. The finding that the satellite cell pool is preferentially affected in fast type II fibers in the elderly [392] has established the idea that stem cell exhaustion is majorly involved in sarcopenia and possibly even facilitates age-associated fast-to-slow transitions [393].…”

The microRNA-mediated gene regulatory network in the hippocampus and hypothalamus of the aging mouse

“…In humans, 60% of protein-coding genes are regulated by miRNAs [17]. Numerous studies have shown that miRNAs play an important role in regulating aging processes, such as cognitive decline, inflammation, and neurodegenerative diseases, in mouse brains [18][19][20]. Li et al [21] analyzed miRNA expression datasets from human prefrontal cortex obtained from individuals aged 2 days to 98 years and proposed that age-related miRNAs play an important role during development and the aging process of the human brain.…”