Role of GH/IGF1 signaling pathway on pro-longevity miRNAs

GH/IGF1信号通路对长寿miRNA的作用

• 批准号: 9581485
• 负责人: MICHAL Mateusz MASTERNAK
• 金额: $ 14.9万
• 依托单位: UNIVERSITY OF CENTRAL FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9581485
• 关键词: Adipocytes; Adipose tissue; Adolescent; Adult; Age; Aging; Animals; Atherosclerosis; Blood Circulation; Caloric Restriction; Cell Nucleus; Cells; Development; Diabetes Mellitus; Diet; Disease; Dwarfism; Elderly; Fatty acid glycerol esters; Follow-Up Studies; Gene Expression; Genes; Genetic; Genetic Transcription; Genotype; Glucose Intolerance; Goals; Growth and Development function; Hormone replacement therapy; Human; IGF1 gene; In Vitro; Incidence; Inflammatory; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Life; Life Style; Link; Longevity; Mediating; Mesenchymal Stem Cells; Metabolic; Metabolic syndrome; MicroRNAs; Mus; Obesity; Organ; Pathway interactions; Phenotype; Phosphorylation; Play; Population; Predisposition; Process; Production; Publishing; Race; Rattus; Regulation; Research; Role; Serum; Signal Pathway; Signal Transduction; Somatotropin; Source; Testing; Time; Transcription Process; Transcriptional Activation; Transplantation; Untranslated RNA; adipokines; adiponectin; age related; base; cytokine; deep sequencing; exosome; growth hormone deficiency; healthspan; healthy aging; hormonal signals; improved; insulin sensitivity; insulin signaling; postnatal; protective factors; receptor; regenerative; resilience; response

The long-goal of this proposal is to identify circulating micro RNA (miRNAs) as potential juvenile protective factors that mediate the effects of somatotropic signaling during postnatal development on healthy aging. With the growing population of elderly people, there is growing incidence of age-related diseases including metabolic syndrome, atherosclerotic disease, insulin resistance and diabetes mellitus. Several studies with mice and rats indicated that obesity causes insulin resistance and has negative effects on longevity. Calorie restriction decreases the volume of fat, improves insulin sensitivity and extends longevity. However, our studies with long-living Ames dwarf (df/df) mice indicated that these growth hormone deficient animals have altered function of adipose tissue promoting healthy phenotype regardless of predisposition to obesity during aging. We propose the general hypothesis hypothesis that alterations in the levels of circulating miRNA species secreted by adipose tissue-derived MSCs link hormonal signaling during development with control of aging. In the proposed studies, we will investigate the effects of growth hormone (GH) and adiponectin on the levels of putative pro-longevity miRNA in circulation and insulin target organs. To test our hypothesis we propose four specific aims: 1. Determine the mechanism by which GH/IGF-1 and adiponectin signaling pathways regulate expression of putative pro-longevity miRNAs in Ames dwarf and normal mice. 2. Determine to what extent MSCs contribute to the release of circulating putative pro-longevity miRNAs in response to GH/IGF-1 or adiponectin. Investigate to what extent exosomes contained in the serum of df/df mice can infiltrate target cells in vitro to reduce production of pro-inflammatory cytokines and adipokines.

该提案的长期目标是鉴定循环微RNA （miRNAs）作为潜在的幼体