Adaptive processes in skeletal muscle: molecular regulators & genetic influences

[Guest guest]

J Musculoskelet Neuronal Interact. 2006 Jan-Mar;6(1):73-86.

Adaptive processes in skeletal muscle: molecular regulators and

genetic influences.

CE, Rittweger J.

Institute for Biophysical and Clinical Research into Human Movement,

Department of Exercise and Sport Science, MMU Cheshire, England, UK.

Skeletal muscle is a highly adaptable tissue. It responds to

environmental and physiological challenges by changes in size, fibre

type and metabolism. All of these responses are underpinned by our

genes and it is therefore generally assumed that genetic variation

between individuals may account for the differences in musculature

and athletic capabilities between people.

Research into the genetic influences of our muscle is at an embryonic

stage, but some early insight into potential regulators has recently

emerged, which is reflected in this review. Broad heritability, which

appears to affect muscle size and strength more than metabolism has

been assessed in twin and sibling studies. It appears to account for

more inter-individual variation in the young as opposed to older

people.

However, the studies reported to date do demonstrate a large degree

of diversity, which is probably predominantly due to different

methodological approaches being adopted as well as distinct

populations being studied.

At a molecular level, there has been enormous progress in identifying

regulators of atrophy and hypertrophy though the study of knock-out

and transgenic animals and also through the utilisation of cell

culture models. Among others, the insulin-like growth factors,

calcineurin, desmin, myf5, mrf4, MyoD and myogenin have been

identified as positive regulators of muscle size, while TNF-alpha,

myostatin and components of the ubiquitin pathway have been

recognized as regulators of muscle wasting.

However, given the ethical and mechanistic constraints of performing

similar studies in humans, difficulties have arisen when attempting

to translate the animal and cell culture findings to humans. However,

the current search for target " exercise genes " in humans has yielded

the first successful results.

Variations in the genes encoding for: the angiotensin converting

enzyme, alpha-actinin 3, bradykinin, ciliary neurotrophic factor,

interleukin-15, insulin-like growth factor II, myostatin and the

vitamin D-receptor have all been found to account for some of the

inter-subject variability in muscle strength or size. However, the

influences of these genetic variations are somewhat weak, and not

always reproducible and furthermore they are predominantly based in

young healthy people.

Hence, a key topic, namely the molecular mechanisms of muscle frailty

in the elderly still remains to be elucidated.