Metabolic flexibility refers to the ability to switch between carbohydrate (CHO) and fat oxidation in response to changing physiological conditions. A mixed-model design is proposed to interrogate the hypothesis that the loss of metabolic flexibility in aging is of mitochondrial origin. The design calls for studies on intact humans, human skeletal muscle (SM) and white adipose tissue (WAT) as well as on rat and mouse SM and WAT. A segment of the effort on cells and organelles isolated from young and old lab rodents will be necessary to perform extensive respiratory control studies as well as studies of mitochondrial dynamics and composition, whereas because of sample size limitations, studies an human mitochondrial preparations will be involve selective analyses. To test the main hypothesis four cohorts of humans will be studied: sedentary (< 2 hr vigorous PA/wk) and physically active (>5 hr PA/wk) young healthy controls (21-35 yr), older sedentary and physically active individuals (60-80 yr) of age. Tissues will be harvested from analogous rat populations, 3-4 month (mo) and 21-23 mo old male and female F344 rats and young (2-3 mo) and old (15 mo) GPR81 null mice (Aim 4).

Public Health Relevance

A mixed-model design is proposed to interrogate the hypothesis that the loss of metabolic flexibility in aging is of mitochondrial origin. The design calls for studies on intact humans, human skeletal muscle (SM) and white adipose tissue (WAT) as well as on rat and mouse SM and WAT. A segment of the effort on cells and organelles isolated from young and old lab rodents will be necessary to perform extensive respiratory control studies as well as studies of mitochondrial dynamics and composition, whereas because of sample size limitations, studies an human mitochondrial preparations will be involve selective analyses.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
3R01AG059715-02S1
Application #
9901270
Study Section
Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Fridell, Yih-Woei
Project Start
2018-08-15
Project End
2021-05-31
Budget Start
2019-07-15
Budget End
2020-05-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94710