Determining the muscle anabolic and anti-catabolic potential of Ursolic Acid in Ageing

This is a 3 year project funded by the MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research (www.birmingham.ac.uk/musculoskeletal-ageing). The project is a cross-institutional collaboration between the University of Birmingham and the University of Nottingham and will be primarily situated at the University of Birmingham in the School of Sport Exercise & Rehabilitation Sciences.

Ursolic acid (UA) is a triterpenoid, enriched in the skin of apples, cranberries and prunes. Recently UA supplementation in mice was shown to increase skeletal muscle hypertrophy i.e. combined with resistance-type exercise, UA synergistically increased the post-exercise activation of the mammalian target of rapamycin complex 1 (mTORC1), a purported central regulator of skeletal muscle hypertrophy. Perhaps more impressively, UA has shown capacity to attenuate muscle loss in a pre-clinical model of disuse atrophy. Collectively therefore, UA has emerged as a unique nutritional compound capable of increasing anabolic/ decreasing catabolic processes in muscle. However, whether these beneficial effects of UA, can translate into humans remains unexplored. Given the paucity of pharmacological or nutritional approaches to promote muscle anabolism (vs. established effects of exercise) we propose to test the effects of UA on muscle mass in a population with an unmet need in terms of muscle maintenance: older aged individuals.

The project will test the hypothesis that UA supplementation will:
1. Augment muscle hypertrophy following 12-weeks resistance exercise training in older individuals.
2. Attenuate declines in muscle mass during 4-weeks de-training in older individuals.
3. Maintain muscle mass during a period of inactivity-induced atrophy in older individuals.

Research Design: Research aim 1 (RA1) will establish a time-course of UA plasma bioavailability and muscle incorporation following UA supplementation at three doses (400, 800 and 1200mg) in fasted, resting conditions. Next, using the optimal dosing strategy developed in RA1, Research aim 2 (RA2) will test whether UA supplementation in combination with 12-weeks resistance exercise training increases skeletal muscle hypertrophy and offsets atrophy during a subsequent 4-weeks de-training. The study will utilize a double-blind, randomized unilateral resistance-exercise training study in 16 older (65-75y) sedentary individuals, randomly assigned to either a UA or placebo group. Research aim 3 (RA3) will examine whether UA supplementation can maintain muscle mass during inactivity-induced atrophy. The study will utilize a double-blind, randomized de-mobilisation approach (4-weeks reduced steps model) in 16 older individuals randomly assigned to either a UA or placebo group. We will measure muscle mass (DXA), function (SPPBT, strength, power) and muscle protein synthesis using our doubly labelled water methodologies.

Person Specification
Applicants should have a strong background in physiology/biochemistry/nutrition. Experience in conducting human based physiological/clinical research is preferable but not required as specific training will be provided through the course of the PhD. Prospective candidates are expected to have or obtain at least an Upper Second Class Honours Degree in a relevant subject.

How to apply
Applications including a CV, names and addresses of two referees and a covering letter should be sent to Alison Fletcher, C/o Research and Knowledge Transfer Office, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT or email [Email Address Removed]

Enquiries can be directed to Dr Andy Philp: Email: [Email Address Removed]

The closing date is Monday 27th January 2014 and Interviews will be held on Thursday 6th February 2014