Overcoming the blunted response to resistance exercise with fish oil to maximise the maintenance of muscle mass in older people

Skeletal muscle is the largest organ in the human body and has many important roles in determining our physical abilities and overall wellbeing. One major function of skeletal muscle is to carry out many daily tasks, such as rising from a chair or getting on a bus, tasks often referred to as functional abilities. During healthy ageing muscle size is reduced by approximately 0.5-2% a year (known as sarcopenia), with concurrent reductions in functional abilities. This can result in a reduction in quality of life and loss of independence, both of which are clearly not desirable. The incidence of sarcopenia is around 20% between 50-70 years and around 50% in those over 80 years, with the absolute numbers and the average age of the population rising.

One method through which we can enhance muscle function and retard the progression of sarcopenia, across all age groups, is through exercise. The effectiveness of exercise will depend on a number of genetic and environmental factors, with nutritional intake being one of the most important and easily altered. Recent research has suggested that altering the type of fatty acids consumed may have a positive effect on muscle function. Little research is yet to be carried out in elderly humans. This is important as that findings from animal models are not definitively transferrable to humans. The main aim of the current proposal, therefore, is to investigate the effect the consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), long chain polyunsaturated fatty acids found in oily fish, on the response to a resistance training programme in the elderly. A further aim is to determine the mechanisms which result in these adaptive responses.

The project will be centred round a large 18 week resistance training/nutritional (EPA/DHA) intervention with both males and females over the age of 65 years. There are three main research questions and experiments stemming from this intervention. 1) Does the consumption of EPA and DHA result in a greater increase in strength, power and functional abilities in response to resistance training? To answer this question a series of measures of muscular performance and functional abilities will be assessed. 2) Does the consumption of EPA and DHA increase the size and quality of muscles, reduce the amount of fat found within the muscle and decrease inflammation? To address this question the participants will have MRI images of their muscles and blood samples taken before and after the intervention. This will allow the calculation of muscle mass/fat content and circulating levels of inflammatory markers. 3) Does the consumption of EPA and DHA enhance the activity of the molecules involved in controlling muscle mass after a single bout of resistance exercise? For this question we will obtain muscle samples before and after a single training session and measure changes in molecules previously identified as important in the changes in muscle mass in response to exercise. A fourth aim running throughout the proposal is 4) Do males and females respond differently to the combination of EPA/DHA and resistance exercise? Differences in protein metabolism have previously been noted between genders and yet the investigation of these differences is often overlooked. We will investigate this by studying responses in groups of males and females.

In summary, the aim of the proposed project is to test the hypothesis that the consumption of fatty acids found in oily fish will improve the response of an elderly population to a resistance training intervention. The major outcome of the proposal would be in establishing a beneficial effect of fish oil on muscular adaptation in the elderly, opening up a widely available therapeutic strategy for an improvement in the quality of life in the elderly population. Such strategies are of particular importance due to the increasing age of the UK population.

Mechanisms and strategies to counteract sarcopenia are beginning to be uncovered. Recent work has suggested that increased consumption of EPA/DHA increases protein metabolism and muscle hypertrophy. However, these studies have generally been carried out in young healthy animals or cancer patients. Our pilot data in elderly women found that EPA/DHA supplementation results in a greater adaptive response in skeletal muscle contractility in response to resistance exercise, highlighting a beneficial effect compared to placebo. Further work has indicated that increased consumption of EPA/DHA can help preserve lean muscle mass, in ageing rats, and identified the PI3K/PDK1/p70s6k pathway as a potential mechanism of action. What remains to be determined is whether these effects are seen in a larger cohort of males and females and to determine the mechanisms behind these effects.

The aims of the current proposal are to investigate the effect of EPA/DHA consumption on skeletal muscle mass, function and anabolic/catabolic signalling during resistance training in the elderly and whether the responses are the same in males and females. These aims will be addressed by determining changes in functional abilities and skeletal muscle contractile properties after a EPA/DHA supplementation and resistance exercise training. The cross sectional area, volume and fat content of skeletal muscle will be assessed by MRI, before and after the intervention, as will systemic levels of inflammatory markers that are implicated in the aetiology of sarcopenia. In muscle samples we will identify changes in signalling protein pathways associated with increases in protein synthesis and decreases in protein breakdown, potentially identifying mechanisms of EPA/DHA action. These studies will establish whether EPA/DHA consumption alongside resistance training can reduce the deleterious effects of sarcopenia and begin to uncover the molecular mechanisms.

The objectives of the current proposal are to:
1) Determine the effect of dietary supplementation with EPA/DHA on the changes in skeletal muscle mass and function and systemic inflammation with 18 weeks of resistance exercise in the elderly.
2)Test the hypothesis that increasing the EPA/DHA content of skeletal muscle membranes in the elderly a) increases anabolic signalling upstream of mTOR, b) downstream of mTOR and/or c) decreases atrophy associated signalling.
A third objective is to determine whether these responses differ between genders.

Succesful completion of these objectives will improve our understanding of sarcopenia, particularly elaborating on the role of skeletal muscle fatty acid content in overcoming the anabolic resistance associated with ageing and sarcopenia. Such findings will be of relevance to human health and could open new avenues through which the functional abilities and quality of life in the ever increasing elderly population can be improved.

Who will benefit from this research?

There is the potential for several groups to benefit from the research entailed within the current proposal. These beneficiaries may include private sector companies that are involved in the fish oil supplementation industry. These include the fishing industry, companies responsible for processing and encapsulating the fish oil and also those involved in the marketing and retail of fish oil products. Another group who may benefit from the research proposal is the elderly population as the proposal aims to uncover mechanisms promoting lifelong health and wellbeing, particularly within this population. Further benefits may be seen within the health sector primarily the NHS who are responsible for the treatment and care of elderly people suffering from sarcopenia and its numerous associated co-morbidities. Concurrent with this there may also be alterations to the policy for fish oil supplementation in the elderly from government agencies such as the food standards agency.

How will they benefit from this research?

If the current hypothesis for the project is confirmed then this project will provide information that can improve the current guidelines for the elderly people to arrest or treat the onset of sarcopenia. Through fish oil supplementation there may be an improvement in the quality of life in this population and, therefore, a decrease in medical treatment due to falls and other disease states associated with a loss of muscle mass. This would be of particular importance due to the countries ageing population and an increase in the incidence/cost of such treatment. This will also, therefore, have a positive economic benefit for the NHS through a reduction in the number of fall related and other disease associated treatments for the elderly. Also improving the ability to live independently in the elderly will lead to a reduction in their reliance on the state for help performing daily tasks, also reducing the economic burden on the UK government. Finally the companies in the fish oil industry may benefit economically if the demand for such supplements is increased, through promotion of these supplements for the elderly population.

Overall the main potential beneficiaries from the current project would be the elderly population who, through a greater preservation of muscle mass, would be able to live more independently and carry out tasks of daily living with greater ease.