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Developmental Programming of Mammalian Aging

哺乳动物衰老的发育规划

基本信息

批准号：
10190763
负责人：
Andrzej Bartke
金额：
$ 22.14万
依托单位：
SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-15 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10190763
关键词：
Address Adipose tissue Adolescence Adolescent Adult Age Age-Months Aging Animals Anti-Obesity Agents Antidiabetic Drugs Body Composition Body Weight Cell Culture Techniques Characteristics Child Childhood Chronic Disease Consumption Development Diabetes Mellitus Disease Dose Energy Metabolism Exposure to Fat-Restricted Diet Future Gene Expression Gene Expression Profiling Goals Growth Health High Fat Diet Hormonal Human Inflammation Insulin Insulin-Like Growth Factor I Intervention Knowledge Laboratories Life Life Style Link Longevity Metabolic Metabolism Metformin Modification Mus Non-Insulin-Dependent Diabetes Mellitus Nutritional Obesity Organism Pharmaceutical Preparations Pharmacology Phenotype Physical Endurance Public Health Resistance Reverse Transcriptase Polymerase Chain Reaction Risk Signal Transduction Stress Temperature Testing Time Tissues Translations Work age related blood glucose regulation carbohydrate metabolism cohort cost diabetic environmental intervention glucose metabolism healthspan healthy aging improved in vivo lifestyle intervention lipid metabolism metabolic phenotype novel novel strategies peripubertal period postnatal postnatal development programs rapid growth response sex transcriptome sequencing treatment group

项目摘要

Abstract It is well known that the risk of adult disease can be altered by factors acting during development, both pre- and postnatally. Recent studies in our laboratory have shown that hormonal intervention limited to six weeks during early postnatal life can alter adult metabolic characteristics and determine how long an animal will live. However, the potential of early life interventions to slow the rate of aging and reduce the risk of age- related chronic diseases has not been adequately explored. The proposed HYPOTHESIS is that interventions during rapid pre- and peri-pubertal growth can produce permanent beneficial changes in carbohydrate, lipid, and energy metabolism, thus promoting healthy aging. This hypothesis will be tested using two pharmacological and one environmental intervention which have already been shown to improve glucose homeostasis in adults and to be well tolerated by juveniles. In three SPECIFIC AIMS, juvenile mice will be treated with metformin, a drug with multiple beneficial effects in adults with type 2 diabetes or with MSI-1436, a novel experimental anti-obesity and anti-diabetic drug, or exposed to a modest reduction of environmental temperature, a safe, cost free and readily translatable intervention. The effects of these three interventions will be tested on glucose homeostasis, energy metabolism, body composition, physical endurance, responses to nutritional stress (high fat diet), and gene expression. Using RT-PCR, multiple tissues will be analyzed for expression of genes mechanistically related to healthspan and longevity, including those related to insulin, GH, IGF-1, mTORC1 and mTORC2 signaling, glucose and lipid metabolism, and inflammation. Unbiased RNA-Seq studies of adipose tissue will also be conducted to search for novel mechanisms linking early life interventions and adult phenotype and aging. Separate cohort of animals from each treatment group will be used for studies of glucose homeostasis, energy metabolism, body composition, and physical endurance at the ages of 24 and 30 months and for determination of longevity. The results will determine whether simple and safe lifestyle interventions during childhood and adolescence can promote extension of healthspan and lifespan and begin to identify mechanisms of developmental programing of mammalian aging and potential targets for pharmacological interventions. Three Specific Aims are proposed: Specific Aim 1: To determine the impact of early life treatment with metformin on adult metabolic characteristics causally related to aging. Specific Aim 2: To determine the impact of early life treatment with MSI-1436 (an experimental anti- obesity drug) on adult metabolic characteristics causally related to aging. Specific Aim 3: To determine the impact of a mild reduction of environmental temperature during early life on adult metabolic characteristics causally related to aging.

摘要

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Insulin signaling in the heart is impaired by growth hormone: a direct and early event.

DOI：
10.1530/jme-21-0242
发表时间：
2022-08-01
期刊：
JOURNAL OF MOLECULAR ENDOCRINOLOGY
影响因子：
3.5
作者：
Munoz, Marina C.;Piazza, Veronica G.;Burghi, Valeria;Giani, Jorge F.;Martinez, Carolina S.;Cicconi, Nadia S.;Muia, Nadia, V;Fang, Yimin;Lavandero, Sergio;Sotelo, Ana, I;Bartke, Andrzej;Pennisi, Patricia A.;Dominici, Fernando P.;Miquet, Johanna G.
通讯作者：
Miquet, Johanna G.

Somatotropic Axis, Pace of Life and Aging.

DOI：
10.3389/fendo.2022.916139
发表时间：
2022
期刊：
Frontiers in endocrinology
影响因子：
5.2
作者：
通讯作者：

Metformin treatment of juvenile mice alters aging-related developmental and metabolic phenotypes.

DOI：
10.1016/j.mad.2021.111597
发表时间：
2022-01
期刊：
Mechanisms of ageing and development
影响因子：
5.3
作者：
Zhu Y;Fang Y;Medina D;Bartke A;Yuan R
通讯作者：
Yuan R

GH deficiency confers protective advantages against Alzheimer's disease through rescued miRNA expression profile in APP/PS1 mice.

GH 缺乏通过挽救 APP/PS1 小鼠中的 miRNA 表达谱，赋予对抗阿尔茨海默氏病的保护优势。

DOI：
10.1007/s11357-022-00633-0
发表时间：
2022
期刊：
GeroScience
影响因子：
5.6
作者：
Noureddine,Sarah;Saccon,Tatiana;Rudeski-Rohr,Trina;Gesing,Adam;Mason,JeffreyB;Schneider,Augusto;Dhabhi,Joseph;Puig,KendraL;Rakoczy,Sharlene;Brown-Borg,HollyM;Masternak,MichalM
通讯作者：
Masternak,MichalM

Hallmarks of Testicular Aging: The Challenge of Anti-Inflammatory and Antioxidant Therapies Using Natural and/or Pharmacological Compounds to Improve the Physiopathological Status of the Aged Male Gonad.