Identification of Serum Factors Responsible for Systemic Mitochondrial Biogenesis

Research Update – October 2013

MitoCanada funding helped to support our initial work towards the identification of serum factors that mediate systemic mitochondrial biogenesis in association with exercise (exerkines).  We have discovered that IL-15 is a major serum factor that promotesmitochondrial biogenesis in many tissues in the human body.  By injecting extremely small amounts of IL-15 to mimic the concentration and pattern seen with exercise, we were able to show about 50% of the benefits derived from exercise including an increase in mitochondrial enzyme activity and an improvement in insulin sensitivity.  This paper is being submitted to Science in mid-November 2013.  We also discovered another exerkine called METRNL and this has very similar functions to IL-15.  IL-15 in combination with METRNL may have additive effects that may be of potential therapeutic benefit and we are now studying this combination.

– Dr. Mark Tarnopolsky

Grant and Project Information

Date:  February 2012

Award: $41,000 (one time)

Identification of Serum Factors Responsible for Systemic Mitochondrial Biogenesis

Mark Tarnopolsky, M.D., Ph.D., FRCP(C); Justin Crane, M.Sc.; Adeel Safdar, Ph.D.; Arkan Abadi, Ph.D.
Neuromuscular and Neurometabolic Clinic,
McMaster University Medical Center

We have shown that long-term endurance exercise provided dramatic clinical protection in essentially all tissues in the body of a mouse model of mitochondrial disease (POLG1 mice).  The protection extended to tissues not traditionally associated with exercise benefits including; gonads, skin, fur, eyes, lung and kidneys.  This indicated that a systemic factor released in response to exercise was acting on distant tissues very much like a hormone.  Our MitoCanada funded research will allow us to further identify these factors.  The funding will partially support two major studies.  The first is a cross-sectional study of 100 men and women between the ages of 20 and 86 with half being well trained athletes and half being sedentary controls.   Analysis of mitochondrial function will be performed on cheek cells, skin, urine sediment (kidney cells) and blood to determine if systemic benefits that we saw in the mice also relate to humans.  The second aspect will be to try and identify the factors which confer systemic mitochondrial protection.  To do this we will be culturing skin cells in the presence of serum from humans at rest and following exercise.  First, we will identify the time of post-exercise where the serum has the beneficial effect on mitochondrial biogenesis and use that serum for proteomic analysis (identifying proteins) that are responsible for the effect.  The long term goal is to identify a protein or proteins that could be injected in patients who cannot exercise to protect the mitochondria in multiple tissues.  Overall, these results are likely to have significant implications for human aging, muscle physiology, exercise science and, most importantly, mitochondrial medicine.