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Alterations in key gluconeogenic regulators with age and endurance training
D B Horn1, D A Podolin, J E Friedman
1Department of Kinesiology, University of Colorado, Boulder 80309-0354, USA.
Metabolism: Clinical and Experimental
|April 1, 1997
Summary
Aging impacts hepatic gluconeogenesis regulators, with fructose 2,6-bisphosphate (F 2,6-P2) increasing and cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity and mRNA decreasing with age. Endurance training did not alter these age-related changes.
Area of Science:
- Metabolism and Aging
- Endocrinology
- Molecular Biology
Background:
- Hepatic gluconeogenesis, a vital metabolic pathway, is known to decline with age.
- Understanding the molecular regulators of this process is crucial for addressing age-related metabolic dysfunction.
- Endurance training is often investigated for its potential to mitigate age-associated physiological changes.
Purpose of the Study:
- To investigate the impact of normal aging and endurance training on key regulators of hepatic gluconeogenesis.
- To examine age- and training-related changes in fructose 2,6-bisphosphate (F 2,6-P2), phosphoenolpyruvate carboxykinase (PEPCK) activity and mRNA, pyruvate carboxylase, and malate dehydrogenase.
Main Methods:
- Male Fischer 344 rats of three age groups (young, middle-aged, old) were subjected to either endurance training or a sedentary lifestyle for 10 weeks.
- Liver tissue was analyzed for F 2,6-P2 levels, cytosolic and mitochondrial PEPCK activity, PEPCK mRNA expression, pyruvate carboxylase activity, and malate dehydrogenase activity.
Main Results:
- F 2,6-P2 levels were significantly elevated in old rats compared to young rats, irrespective of training.
- Cytosolic PEPCK activity and PEPCK mRNA expression showed significant age-dependent declines.
- Endurance training did not significantly alter any of the measured regulators of hepatic gluconeogenesis across age groups.
Conclusions:
- Age-related decreases in hepatic gluconeogenic capacity are partly attributable to changes in F 2,6-P2, cytosolic PEPCK activity, and PEPCK mRNA.
- Mitochondrial PEPCK, malate dehydrogenase, and pyruvate carboxylase activities are not significantly affected by aging in this model.
- The mechanisms by which endurance training might attenuate age-related declines in gluconeogenesis remain to be elucidated, as training did not impact the studied regulators.