The researchers found that so-called AMP-activated protein kinase (AMPK) slows down in the skeletal muscle of 2-year-old rats relative to 3-month-old rats. A chief regulator of whole-body energy balance, AMPK in skeletal muscle stimulates the oxidation of fatty acids and the production, or biogenesis, of power-producing mitochondria that burn fat and fuel cells,according to the researchers.
The new findings might help to explain "what happens as we age," said Gerald I. Shulman, a Howard Hughes Medical Institute investigator at Yale University School of Medicine.
Why does AMPK decline as we age? Is the decline an adaptation because the muscle's mitochondria become too damaged?
In response to exercise and other stimuli older rats produced far less AMPK.
In the current study, the researchers set out to determine whether the declining mitochondrial function and increased intracellular fat content seen with aging could be traced back to deficiencies of AMPK. They compared AMPK activity in young and old rats following three "perturbations" that normally stimulate the enzyme and, in turn, mitochondria production. The treatments included acute exposure to an AMPK-stimulating chemical, chronic exposure through feeding of another chemical that induces AMPK by mimicking an energy shortage, and exercise.
In every case, older rats showed a decline in AMPK activity compared to younger animals. Young rats infused with a stimulatory chemical showed an increase in muscular AMPK activity not seen in old rats, they found. Similarly, the muscle of exercise-trained young rats showed more than a doubling in AMPK activity. In older rats, that AMPK hike with exercise was "severely blunted." The muscles of young rats fed the AMPK-stimulating chemical also showed an increase in AMPK and a 38% increase in mitochondrial density, they reported. In contrast, older animals' AMPK activity and mitochondrial numbers held steady.
As we get older exercise becomes less effective. Plus, a low level of AMPK might put us at greater risk of type 2 insulin insensitive diabetes.
Would a drug or gene therapy that stimulates AMPK production increase muscle strength and decrease fat? Would it come at some cost? Does the body slow down AMPK production because the muscle cells become too aged to do as much? Or would higher AMPK increase cancer risk?
|Share |||Randall Parker, 2007 February 06 11:22 PM Aging Mechanisms|