Skeletal muscle represents the largest organ in the body, comprising >50% of total body mass.
The function of skeletal muscle is best understood for its role in locomotion and providing
mechanical support to the skeleton to facilitate movement. However, skeletal muscles are also
important for maintaining whole-body metabolic health. For example, muscles also act as a
site for glucose disposal thereby acting to maintain whole-body glycaemic control. In
addition, skeletal muscles represent a vast protein store, the amino acids from which can be
used in times of fasting, infection and disease to provide energy to maintain other critical
organs. Exercise (resistance type exercise (RE-T) in particular) still remains the most
effective means by which to maintain and increase muscle mass through stimulation of muscle
protein synthesis (MPS), despite this, how exercise regulates these changes in muscle mass is
still unknown. A number of pathways have been inferred as key, however it is clear from a
number of studies that systemic hormone levels, testosterone in particular, may provide a
significant contribution. It is well known that chronic androgenic hormone deficiency can
lead to a loss of lean body mass and strength, which can in turn contribute to impaired
physical function. Furthermore, when testosterone levels are pharmacologically reduced (using
a gonadotropin releasing hormone analogue) in healthy young males, resistance exercise
training induced increases in muscle mass and strength are absent. Whilst systemic hormone
levels are carefully maintained in youth (unless illness or deficiency is present), levels of
these hormones decrease with age, particularly in those that are not regularly physically
active, indeed approximately 25-30% of older men have levels of testosterone which are below
the threshold used to define hypogonadism. Therefore, there is significant need to understand
the underlying mechanisms behind hormonally induced muscle mass regulation. Furthermore, in
older age there is a resistance to traditional anabolic stimuli such as nutrition or
resistance exercise, with older adults showing a blunted-anabolic hormonal profile in
response to resistance training compared to young. These impairments to hormonal regulation
with ageing may in part be responsible for the slow decline in muscle mass with age known as
sarcopenia. Whilst all muscle-wasting conditions are of considerable concern, it is the loss
of muscle in older age that poses the greatest socio-economic burden. Therefore there is a
significant clinical need to identify contributing factors to this muscle loss so that they
can be specifically targeted for intervention (i.e., pharmacological hormonal therapies).
The aims of this project are two fold: 1) Firstly we aim to investigate the impact of
systemic hormone levels on control of muscle mass in healthy young adults undertaking a
resistance exercise training program, we hypothesize that reduction of hormone levels in
systemically normal young adults will impair MPS and muscle mass gains in response to
resistance exercise training. 2) Secondly we aim to investigate the impact of enhancing
testosterone levels in older adults on responsiveness to resistance exercise training and the
contribution of systemic testosterone levels to muscle mass regulation in ageing, we
hypothesize that increasing testosterone levels in older males will improve responsiveness to
anabolic stimuli (RE-T).