MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice

Abstract

MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3’ untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself. Here, we have measured the expression levels of 521 small regulatory microRNAs (miRNAs) in spleen tissue from young and old animals of 6 mouse strains with different median strain lifespans by quantitative real-time PCR. Expression levels of 3 microRNAs were robustly associated with strain lifespan, after correction for multiple statistical testing (miR-203-3p [β-coefficient = −0.6447, p = 4.8 × 10−11], miR-664-3p [β-coefficient = 0.5552, p = 5.1 × 10−8] and miR-708-5p [β-coefficient = 0.4986, p = 1.6 × 10−6]). Pathway analysis of binding sites for these three microRNAs revealed enrichment of target genes involved in key aging and longevity pathways including mTOR, FOXO and MAPK, most of which also demonstrated associations with longevity. Our results suggests that miR-203-3p, miR-664-3p and miR-708-5p may be implicated in pathways determining lifespan in mammals.

The Cross-Talk Between Sphingolipids and Insulin-Like Growth Factor Signaling: Significance for Aging and Neurodegeneration

“…mTORC1 inhibitor rapamycin is an extremely robust pharmacological treatment that extends lifespan in multiple model organisms, including mammals, even if administered relatively late [ 185 ]. Mutation analysis and microRNA research confirm the role of mTOR [ 188 , 189 ]. The outstanding universality of the lifespan effects of rapamycin have led to suggestions about potential human intervention candidate [ 185 ].…”

MiR-664a-3p expression in patients with obstructive sleep apnea

“…In fact, both the role and mechanism of miR-664 in disease have been investigated in several studies. [ 25 – 28 ]…”

The Role of MicroRNAs in Influencing Body Growth and Development

“…These concepts are further supported by a study in adulthood showing that age-related miRNAs are related to immune response and regulation of cellular metabolism [23], revealing that miRNAs regulate genes involved in age-related biological mechanisms. Furthermore, miRNA expression has been shown to change significantly in body tissues with age, and different miRNA profiles have been related with longevity in a broad spectrum of animal species, from Caenorhabditis elegans to humans [24][25][26], as reported in depth below.…”