Does Human Skeletal Muscle Possess an Epigenetic Memory of Testosterone?

Norwegian School of Sport Sciences45 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Healthy Aging Age-Related Sarcopenia Testosterone Deficiency

SalineDRUG

Two placebo injections one at baseline and one week 3.

Testosterone UndecanoateDRUG

Two testosterone undecanoate injections, 1000 mg/4 ml at baseline, 500 mg/2 ml at week 3.

Saline + Resistance exercise trainingDRUG

Two placebo injections one at baseline and one week 3 and10 weeks of supervised, structured, progressive resistance training.

Testosterone Undecanoate + Resistance exercise trainingDRUG

Two testosterone undecanoate injections, 1000 mg/4 ml at baseline, 500 mg/2 ml at week 3 and 10 weeks of supervised, structured, progressive resistance training.

Eligibility

Sex: MALEMin age: 55 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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