The Gene SMART Study aims to identify genes and molecular mechanisms underlying the variable response to 12 weeks of high intensity exercise training.

The study is ongoing; male and female participants are welcome.

About the Gene SMART study

Most Australians are overweight and do not meet the national recommendations for physical activity, which increases the prevalence of many chronic diseases. Alongside diet, exercise plays an essential part in tackling the increasing burden of chronic disease, and increasing the number of years spent in good health. However, people have a remarkably different response to similar exercise, and the factors that underpin these differences are unclear. 

The Gene SMART (Skeletal Muscle Adaptive Response to Training) Study, led by Professor Nir Eynon and his group (Genetics and Epigenetics of Exercise),  is a tightly controlled exercise training study that aims to identify genes and molecular mechanisms (e.g., epigenetics) contributing to healthy ageing, and sex-specific differences in response to exercise.

The Gene SMART Study is ongoing and is supported by Australian Research Council (ARC) and the National, Health and Medical Research (NHMRC) funding. 

Media appearances

The Gene SMART Study and researchers have appeared in the following videos and websites:

Benefits of participating in this study

The study is ongoing and still open to male and female participants. Results from past and current participants are being analysed. 

We are looking for 18- to 65-year-old men and women to participate in a 12-week high-intensity exercise program to assess their Skeletal Muscle Adaptive Response to Training (SMART).

As a research participant you will:

  • be offered a cash reimbursement of $200 for your time
  • train in state-of-the-art facilities at our Footscray Park Campus supervised by qualified sport scientists with years of experience
  • be provided with feedback on your performance in various fitness tests (for example VO2max) and gain a greater understanding of your own fitness
  • potentially gain significant fitness improvements.

From your participation in this project you will also gain experience and knowledge on how physiology and molecular studies are undertaken, which might be beneficial for your own understanding of the human body.

What participants are required to do

Participants are asked to perform exercise testing and training 3 times per week for approximately 18 weeks.

This involves the following phases:

  • familiarisation and baseline fitness assessment tests
  • control phase: 4 weeks
  • training phase: 12 weeks
  • post-intervention fitness testing.

You'll need complete the following:

  • fill out an informed-consent form and exclusion criteria questionnaires (15 minutes)
  • a 20km time trial on a stationary cycling ergometer (approx. one hour)
  • a graded-exercise test and maximal-oxygen-uptake test on a stationary lode bike (approx. one hour).

This phase takes place over one week.

You'll complete these exercises and tests:

  • two graded-exercise tests and maximal-oxygen-uptake tests (approx. one hour each)
  • control muscle biopsy and blood sampling (approx. 45 minutes).

Over 4 weeks you'll carry on with your usual activity level, wearing an activity monitor for 2 weeks.

After the control phase, the initial testing will be performed again to assess any changes to your fitness from your regular activity levels.

You'll complete these exercises and tests:

  • two graded-exercise tests and maximal-oxygen-uptake tests (approx. one hour each).

Once control testing is complete, you'll begin the 12 weeks of High Intensity Interval Training (HIIT).

You'll complete these exercise sessions and tests:

  • three exercise trial biopsies during the first HIIT session (approx. 4 hours)
  • 12 weeks (3 times a week) of further HIIT sessions (25 to 45 minutes).

Once the 12 weeks of training is finished, you'll have the final testing and biopsy.

You'll complete these exercise sessions and tests:

  • resting biopsy and blood sampling (approx. 45 mins)
  • two graded-exercise tests and maximal-oxygen-uptake tests (approx. one hour each).

Explanation of the tests & training sessions in this study

There are a variety of tests and training sessions used in this study.

Graded-exercise tests (GXT) & maximal-oxygen-uptake (VO2max) tests involve cycling on a stationary lode bike.

You'll cycle for four-minute stages of progressively increasing intensity, with 30-second rest periods.

The total time required to complete this test is approximately one hour.

This test will be used to determine the intensity at which you will be training. Seven minutes after the end of the GXT, you'll perform a VO2max.

For this test you will cycle continuously at an intensity slightly greater than that at which you stopped during the graded-exercise test. The test ends when you can no longer keep up the required pace, and will take no longer than five minutes to complete.

Throughout this test you will wear a mask which we will use to analyse the air you breathe out. This will allow us to determine your maximal oxygen uptake, which is essentially a measure of your aerobic fitness.

Training sessions are completed on an electronically-braked cycle ergometer (Velotron, Racer Mate Inc, Seattle, USA) preceded by a 5-minute warm up.

Each session will consist of 8-14 two-minute intervals performed at different intensities interspersed with 1-minute recovery periods (work-to-rest ratio of 2:1).

To maintain progression, we will change the number of intervals per session and the intensity (resistance).

The purpose of a muscle biopsy is to examine the muscle in detail using a number of techniques we have available.

A qualified and experienced medical doctor will perform each muscle biopsy. The technique involves first cleaning the skin above the part of your thigh where the biopsy is taken.

A local anaesthetic is injected into the skin where the biopsy will be taken. This will cause a slight stinging sensation. Once the numbness has set in a small incision is made with a scalpel, and the biopsy needle is inserted into your thigh muscle, and a small amount of muscle is taken out (maximum of 0.2 gram).

The biopsy takes about ten seconds and you'll feel some pressure in your leg and possibly some pain during the procedure. Pressure is then applied to the muscle to ensure there is minimal swelling.

Contact the project team

Professor Nir Eynon, Project Lead
Email: [email protected]
Phone: +61 3 9919 5615

PhD candidates

Top 10 are listed on this page.

See all of our publications on the research repository. For other publications, please see:

From most recent:

  1. Voisin S, Jacques M, Landen S, Harvey NR, Haupt LM, Griffiths LR, Gancheva S, Ouni M, Jähnert M, Ashton KJ, Coffey VG, Thompson JM, Doering TM, Gabory A, Junien C, Caiazzo R, Verkindt H, Raverdy V, Pattou F, Froguel P, Craig JM, Blocquiaux S, Thomis M, Sharples AP, Schürmann A, Roden M, Horvath S, Eynon N. Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle. J Cachexia Sarcopenia Muscle. 2021 Aug;12(4):1064-1078. doi: 10.1002/jcsm.12741. Epub 2021 Jun 30. PMID: 34196129
  2. Jacques M, Landen S, Alvarez Romero J, Yan X, Garnham A, Hiam D, Siegwald M, Mercier E, Hecksteden A, Eynon N, Voisin S. Individual physiological and mitochondrial responses during 12 weeks of intensified exercise. Physiol Rep. 2021 Aug;9(15):e14962. doi: 10.14814/phy2.14962. PMID: 34327858
  3. Williams CJ, Li Z, Harvey N, Lea RA, Gurd BJ, Bonafiglia JT, Papadimitriou I, Jacques M, Croci I, Stensvold D, Wisloff U, Taylor JL, Gajanand T, Cox ER, Ramos JS, Fassett RG, Little JP, Francois ME, Hearon CM Jr, Sarma S, Janssen SLJE, Van Craenenbroeck EM, Beckers P, Cornelissen VA, Howden EJ, Keating SE, Yan X, Bishop DJ, Bye A, Haupt LM, Griffiths LR, Ashton KJ, Brown MA, Torquati L, Eynon N, Coombes JS. Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study. J Biomed Sci. 2021 May 13;28(1):37. doi: 10.1186/s12929-021-00733-7. PMID: 33985508
  4. Hiam D, Landen S, Jacques M, Voisin S, Alvarez-Romero J, Byrnes E, Chubb P, Levinger I, Eynon N. Osteocalcin and its forms respond similarly to exercise in males and females. Bone. 2021 Mar;144:115818. doi: 10.1016/j.bone.2020.115818. Epub 2020 Dec 16. PMID: 33338665.
  5. Harvey NR, Voisin S, Lea RA, Yan X, Benton MC, Papadimitriou ID, Jacques M, Haupt LM, Ashton KJ, Eynon N, Griffiths LR. Investigating the influence of mtDNA and nuclear encoded mitochondrial variants on high intensity interval training outcomes. Sci Rep. 2020 Jul 6;10(1):11089. doi: 10.1038/s41598-020-67870-1. PMID: 32632177
  6. Voisin S, Harvey NR, Haupt LM, Griffiths LR, Ashton KJ, Coffey VG, Doering TM, Thompson JM, Benedict C, Cedernaes J, Lindholm ME, Craig JM, Rowlands DS, Sharples AP, Horvath S, Eynon N. An epigenetic clock for human skeletal muscle. J Cachexia Sarcopenia Muscle. 2020 Aug;11(4):887-898. doi: 10.1002/jcsm.12556. Epub 2020 Feb 17. PMID: 32067420
  7. Jacques M, Kuang J, Bishop DJ, Yan X, Alvarez-Romero J, Munson F, Garnham A, Papadimitriou I, Voisin S, Eynon N. Mitochondrial respiration variability and simulations in human skeletal muscle: The Gene SMART study. FASEB J. 2020 Feb;34(2):2978-2986. doi: 10.1096/fj.201901997RR. Epub 2020 Jan 9. PMID: 31919888
  8. Hiam D, Smith C, Voisin S, Denham J, Yan X, Landen S, Jacques M, Alvarez-Romero J, Garnham A, Woessner MN, Herrmann M, Duque G, Levinger I, Eynon N. Aerobic capacity and telomere length in human skeletal muscle and leukocytes across the lifespan. Aging (Albany NY). 2020 Jan 3;12(1):359-369. doi: 10.18632/aging.102627. Epub 2020 Jan 3. PMID: 31901896
  9. Smith C, Voisin S, Al Saedi A, Phu S, Brennan-Speranza T, Parker L, Eynon N, Hiam D, Yan X, Scott D, Blekkenhorst LC, Lewis JR, Seeman E, Byrnes E, Flicker L, Duque G, Yeap BB, Levinger I. Osteocalcin and its forms across the lifespan in adult men. Bone. 2020 Jan;130:115085. doi: 10.1016/j.bone.2019.115085. Epub 2019 Oct 14. PMID: 31622778.
  10. Harvey NR, Voisin S, Dunn PJ, Sutherland H, Yan X, Jacques M, Papadimitriou ID, Haseler LJ, Ashton KJ, Haupt LM, Eynon N, Griffiths LR. Genetic variants associated with exercise performance in both moderately trained and highly trained individuals. Mol Genet Genomics. 2020 Mar;295(2):515-523. doi: 10.1007/s00438-019-01639-8. Epub 2020 Jan 2. PMID: 31897802.