Power-Boosting Signal In Muscle Declines With Age

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Power-Boosting Signal In Muscle Declines With Age

http://www.medicalnewstoday.com/medicalnews.php?newsid=62597

As people age, they may have to exercise even harder to get the

benefits afforded to younger folk. That's the suggestion of a report

in the February issue of the journal Cell Metabolism, published by

Cell Press, showing that a signal that gives muscles a kind of

metabolic boost in response to exercise is blunted in older animals.

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 Medical Institute

investigator at Yale University School of Medicine.

Earlier studies have shown that, in comparison to 20-year-old

adults, even lean and healthy people in their seventies show a

higher incidence of fat buildup in their muscle and livers and a

deficiency in mitochondrial function, Shulman explained. These

metabolic shifts have been implicated in the increased prevalence of

insulin resistance and type 2 diabetes that occurs with aging.

" The message of this paper is that, with aging, the AMPK pathway has

reduced activity, " Shulman said. " So, one probably has to work

harder to maintain the same level of fat oxidation and mitochondrial

biogenesis in muscle. "

The number of mitochondria within muscle largely determines its

metabolic capacity. The mitochondrial composition of fibers in

different muscles corresponds to the jobs that they do, and muscle

can be " reprogrammed " through exercise.

For example, Shulman said, the skeletal muscles of marathon runners

typically have much greater mitochondrial content and a greater

capacity to burn fat. Those properties can most likely be attributed

to chronic activation of the AMPK pathway.

" In regards to insulin resistance and type 2 diabetes, having more

AMPK activity in our skeletal muscle is probably a good thing

because AMPK activation stimulates glucose uptake, increases fat

oxidation, and promotes mitochondrial biogenesis, " he said.

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.

" These results suggest that aging-associated reductions in AMPK-

stimulated activity may be an important contributing factor in the

reduced mitochondrial function and dysregulated intracellular fat

metabolism associated with aging-induced insulin resistance and type

2 diabetes, " the researchers concluded.