In an effort to attain biceps like Madonna and that illusive ‘washboard' stomach, you've joined the gym and stuck to a rigorous
training programme. You're looking good and feeling great. However, in order to maintain this newly toned physique you are faced with the daunting realisation that a future of weight-lifting, muscle crunching diligence lies ahead. Don't slump despairingly into that fruit smoothie just yet though as help could be at hand. A report by Caroline Williams writing in New Scientist Magazine (Vol. 191 No. 2567) reveals that researchers studying the build-up and breakdown of muscle believe that they are close to creating a drug that will prevent the body from dismantling muscle when it is not being used. While this may represent a ray of hope for gym bunnies everywhere, the researchers' primary aims are to tackle weakness in the sick and the elderly and to assist in the feasibility of long space flights for humans.
For most people, muscle growth and breakdown exist in a subtle balance. However, if injury or illness puts our bodies out of action, or indeed if the body becomes starved of food, this balance shifts and muscle breakdown outweighs synthesis. Wasting – or atrophy – presents a serious problem for people confined to bed for long periods or for astronauts who live in micro-gravity. Once enough muscle has been lost, exercise becomes increasingly difficult, leading to a vicious cycle of disuse and further atrophy.
Throughout the 1980's and 1990's, a team of cell biologists at Harvard University, led by Alfred Goldberg, discovered that rather than being a passive side-effect of muscle disuse, muscle atrophy is in fact an active process involving the ubiquitin-proteasome pathway (UPP), that is the disposal machinery used to break down unwanted
proteins in the cell (New Scientist 17 December 2005, p 36). Williams explains that once the process has been activated – regardless of the trigger - ubiquitin ‘destroy me' labels are added to muscle proteins. These ‘tagged' proteins are then fed into the proteasome, a barrel-shaped multi-protein complex that breaks proteins down into their component amino acids for re-use. This process does not reduce the number of muscle cells but rather breaks down the muscle filaments within cells, making them thinner and weaker.
Further studies have shown that at least 90 genes are involved in atrophy, which Goldberg refers to as ‘atrogenes'. While it is still unknown which of these genes trigger atrophy, it has become clear that two of them are essential to the process. Known as Atrogin 1 and muRF1, they ‘code' for the enzymes that attach the destruction labels to proteins. These genes are barely active in normal muscle but their presence increases dramatically in sick animals: Knock out either gene completely and muscle wasting all but stops.
In May 2006, a team from Purdue University, Indiana found that when muscle atrophy sets in there is an increase in the activity levels of the gene erg1. A potential treatment was found in an anti-histamine drug – Astemizole - which was found to block the erg1
channels. However, not only did it block the erg1 channels in skeletal muscle but also in heart muscle, potentially causing an arhythmia known as ‘long QT' syndrome which could lead to sudden death. Given the serious risk, Astemizole was withdrawn from the market in 1999. If this approach is to succeed, researchers will have to find a way to target erg1 in skeletal muscle without blocking erg1 channels in the heart (which consist of both erg1a and erg1b sub-units).
In the meantime, research has continued into focusing on the proteins that turn other genes on or off. In 2004, the Harvard team discovered a transcription factor protein called ‘Foxo' that controls the activity of many atrogenes. Disabling Foxo blocks atrophy and all of the evidence thus far suggests that it may be a good target for future therapies.
In what appears to be a completely opposite approach, overed that pharmaceutical company Wyeth of Madison, New Jersey recently began trials in people with muscular dystrophy using an antibody therapy designed to stimulate muscle growth rather than inhibit atrophy. While muscle growth promotion is very different to attempting to prevent muscle wasting, Williams believes that the end result could be virtually the same and that the two pathways involved are likely to be linked.
It isn't just the sick and elderly who will benefit from the development of anti-wasting drug therapies however. The prospect of preventing atrophy is also of considerable interest to NASA, particularly in view of its much-hyped mission to Mars: By the time an astronaut would have travelled the distance to the Red Planet they can expect to lose up to 25% of their muscle mass and be too weak to even walk, let alone carry-out repairs.
While there are an abundance of valid medical and space-related applications for anti-wasting drugs, their development will inevitably also be of huge interest to athletes as a safer alternative to steroids. Muscle size is not everything though and drugs that maintain strength will not keep a body fit or provide any of the other innumerable benefits of exercise from stronger bones to smarter brains. As we await the arrival of a ‘gym in a bottle', it seems that for the moment at least, there's still no substitute for sticking to that programme and pumping iron.
This abstract was checked by WhiteSmoke Solution. Learn more.