Does Human Skeletal Muscle Possess an Epigenetic Memory of Testosterone?

Does Human Skeletal Muscle Possess an Epigenetic Memory of Testosterone?

This project's primary aim of this double-blinded, randomised, placebo-controlled trial is to investigate whether short-term testosterone administration +/- resistance exercise training induces a muscle memory response that can lead to longer-lasting benefits in aged human skeletal muscle.

The investigators will provide older men with the anabolic hormone, testosterone or placebo, with or without resistance training, followed by a period of testosterone abstinence and detraining, followed by a subsequent repeated period of resistance training (retraining). This will help determine if earlier encounters with short-term testosterone administration can be "remembered" and if adaptation to later retraining can be enhanced as a consequence of encountering testosterone earlier.

Inclusion Criteria:

• Sedentary males
• 55-70 years old
• Serum testosterone levels >8 nmol/L measured in the morning
• Without any known illness, disease or other conditions
• Undergone screening through medical questionnaire, physical examination, routine blood tests and urine sample
• Written informed consent received

Exclusion Criteria:

• Current or previous participation in a formal exercise regime
• A BMI < 18 or > 30 kg·m2
• Hypersensitivity to the study drug or to any of its constituents
• Active cardiovascular disease: uncontrolled hypertension (BP > 160/100 mmHg), angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt, recent cardiac event
• Family history of early (<55y) death from cardiovascular disease
• Haematocrit >50%
• Malignancy
• Prostate-specific antigen (PSA) >4 ng/mL
• Lower urinary tract symptoms
• Taking beta-adrenergic blocking agents, statins, non-steroidal anti-inflammatory drugs
• Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial), epilepsy
• Respiratory diseases including: pulmonary hypertension, chronic obstructive pulmanary disease (COPD), asthma, sleep apnoea
• Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, type 1 or 2 diabetes
• Active inflammatory bowel or renal disease
• Current or previous steroid treatment or hormone replacement therapy
• Clotting dysfunction
• Musculoskeletal or neurological disorders
• Alcohol or drug abuse
• Receiving oral anticoagulants
• Serum testosterone levels above the reference range for 50 year olds (>32 nmol/L) (Bjerner et al., 2009) measured in the morning 1