Wednesday 4 April 2018 10:04am
Associate Professor Phil Sheard spends his time researching the outer limit of what you would call ‘the brain’; he and his lab examine the muscles or, more specifically, the nerves that activate the muscle fibres and how their relationship changes with age. “You lose 1-2% of muscle mass per year from the age of 50,” Phil says, “but I suspect that the process starts much earlier.” This weakening of the muscle is called sarcopenia, a word that literally translates to ‘poverty of the flesh’, and as our population ages this normal part of the ageing process is becoming a larger and larger issue.
Sarcopenia is a major reason for falls in the elderly population, and as such is a major contributor to disability and mortality in those over 65. “The imperative to understanding ageing,” Phil says, “is not to help us to live longer, but to allow us to retain our cognitive and physical independence for longer.” Muscle weakness, and the potentially disabling effects of a fall, can rob people of their independence. “To get your groceries, to lift yourself out of the bath, to make a cup of tea… to do all these things that are the business of being alive,” Phil says, “you need reasonable strength, endurance, and coordination.” By understanding why this strength, endurance, and coordination is progressively lost with age Phil and his team hope to help people remain independent for longer.
So, why do we lose muscle mass as we age? The answer is similar to why people lose muscle mass when they stop exercising. Your muscles are made up of individual muscle fibres that work together to generate force. Each fibre is activated by a branch of a nerve cell, so all of the muscle fibres contract in tandem when the nerve cell is activated. The more you use a muscle the more often those muscle fibres are activated and the stronger the fibres become. You don’t gain or lose the fibres themselves, just increase or decrease the amount of force they can produce. If you don’t use your muscles these fibres begin to wither, a process called atrophy, and while they won’t die off they won’t be able to generate as much force.
As we age our muscles begin to undergo atrophy, mainly due to loss of contact with the nerves that control the activity of muscle fibres. Without those nerves the muscle fibre can’t contract, and so it shrinks due to disuse. This process is slowed by consistent exercise regimes, but at its core the problem is not with the muscle but with the nerve.
Whether in your brain or your body, nerve cells generally have to last for your entire life. For the most part, nerve cells that die are not replaced. This can mean that the skills and senses that we enjoy for most of our lives can be lost along with the nerve cells that mediated those functions. After realising that the problem is with the nerve and not the muscle, Phil and his team decided to ask why some old nerve cells die, and to answer the question they set their sights on the core of the nerve; the cell body. This is where all of the cellular machinery is, so anything that is causing the nerve to fail or breakdown should be here. The problem, they found, was in the nucleus.
The nucleus of a cell holds your DNA, the instruction manual for the production of proteins. In order to regulate the production of proteins the cell must be very protective of the DNA, and so only very specific substances are allowed in or out of the nucleus via channels in the nuclear envelope. “We found that the long-lived proteins that provide the controlled gateways through which substances traverse the nuclear envelope begin to break down with age, which makes the nucleus leaky,” Phil says, “this leads to a loss of integrity of the nuclear barrier, harming transcription and more generally harming the neuron.” This harm to the core of the neuron can cause it to fail, to retract its terminals, and to die. When those things happen the muscles become less active and undergo atrophy, and then you have sarcopenia.
Luckily, it’s not all bad news. In the same way that exercise strengthens the connection between muscle fibre and neuron, exercise appears to reduce the leakiness of the nucleus. It’s not a cure-all, and it certainly can’t erase the effects of age, but exercise can reduce and even reverse a significant amount of sarcopenia. The key is to do something regularly. Many of the mice in Phil’s study chose to run remarkable distances, but interestingly those that ran a long way and those that ran only a little all seemed to experience a significant exercise-related benefit. Running a marathon every day isn’t sustainable for most people, but a daily walk might be. The simple message is that we should do what we can to be a little more active. Our muscles, and nerves will thank us by sticking around longer into our old age.