Sirtuins and Marathon Running: No Pain No Gain?

This post was chosen as an Editor's Selection for ResearchBlogging.orgOn Saturday I ran 12 miles. “Well, at least I have staved off apoptosis in my peripheral blood mononuclear cells” I thought as I hobbled down the stairs on Sunday morning. Normally I don’t think about mononuclear cells on Sunday mornings, only of coffee. However, a paper published last week in BMC Physiology changed that for me, at least temporarily.

Ankle band at the Courir Pour Elles run/walk recently.

The paper, by Marfe et al, investigated whether the physiological stress associated with strenuous exercise may cause apoptosis and contribute to loss of lymphocytes. This paper investigated whether apoptosis is increased in cells of the immune system after running a marathon. The authors studied the expression of various stress-related proteins in peripheral blood lymphocytes in 10 male amateur runners, examining the expression of various antioxidants, stress proteins and apoptotic markers before and after (2-hours post-race) running a marathon. They found that expression of the apoptotic marker bax was decreased significantly after the marathon, while levels of antiapoptotic bcl-2 RNA increased. The amount of propcaspase 9 did not change pre and post race, indicating that there was no change in levels of apoptosis before and after the race.

Expression of the stress-associated proteins HSP70, and HSP32 increased substantially after the marathon, as did levels of the antioxidants Cu-Zn-SOD and Mn-SOD. Transcription of the sirtuin family protein SIRT1 was also increased after the marathon, but levels of SIRT3 and SIRT4 decreased.

So, this paper showed that apoptosis did not occur after the stress of running a marathon and, for the first time, showed that exercise modulates expression of sirtuin family proteins in people.

What does this mean?
Sirtuins are known to be part of a signaling system that enhances survival during times of stress. They are thought to be involved in the observed increases in lifespan associated with calorie restriction in yeast, drosophila and nematodes (1). SIRT1 is a key regulator of cellular metabolism, being involved in insulin signaling, glucose metabolism, and response to reactive oxygen species, to name but a few. SIRT1 activators include calorie restriction (2), which is known to be associated with increased lifespan in certain species, and controversially, resveratrol (3), the proposed anti-aging ingredient in red wine.

Consequently, there has been a lot of interest in the potential of sirtuin activators as anti-aging (or healthy aging) drugs. The search is on for SIRT activators that may have benefit in treatment of diseases associated with aging such as type 2 diabetes (4) and certain cancers (5). This recent study in mice showed that:

..old Sirt1-transgenic mice are partially protected from the development of pathologies typically associated with ageing, such as glucose intolerance, osteoporosis and poor wound healing (5).

Given their role as part of the response to stress, and their implied benefits in healthy aging, it is perhaps not surprising that the oxidative stress arising as a result of marathon running results in sirtuin activation. The paper by Marfe et al adds an interesting facet to the sirtuin story. SIRT1 is activated by the stress associated with strenuous exercise and responds by inducing protective mechanisms to enhance cell survival. So now, in addition to calorie restriction and red wine (resveratrol), we can add marathon running to the list of SIRT1 activators.

The role of sirtuins in cellular metabolism is undoubtedly complex and still to be fully understood. They may have huge potential for understanding and treating diseases associated with aging. As far as a miracle anti-aging pill or fountain of youth? That is up for debate. One message of the sirtuin story so far may simply be this: No pain, no gain. There are no easy answers. And that is the message that resonates with the runner.


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Isobel Maciver

Isobel Maciver

Isobel is a graduate of the University of Edinburgh and of Aston University in Birmingham, U.K. She is a technical writer and editor, and is also manager of the Scientific Communications group at Promega. She enjoys writing about issues in science and communication.


  1. Because at least three of the SIRT genes show a response in terms of gene expression after the marathon, it indicates that genetic differences in these genes may be found and that those differences may lead to allele-specific responses to long-distance running. There are many papers in the body of scientific literature that show gene-by-physical activity interactions. One example shows that higher levels of physical activity may be protective for HDL-cholesterol (“good” cholesterol) concentrations while low activity puts an individual at risk, according the alleles of a specific variant of gene LIPG (endothelial lipase). See Thus, one can imagine SIRT gene polymorphisms where one allele confers the benefits observed and other alleles do not.

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