Heat Shock Proteins and Exercise in Humans

Heat shock proteins (HSPs) are increasingly seen as important players in the response of our biochemistry to stresses and damage. HSPs are fundamentally chaperones and monitors: they look for damaged proteins that can compromise cellular functions and help to ensure that those proteins are rapidly recycled. When events - such as exposure to heat, hence the name - cause damage in our cells, HSP activity increases for a while to compensate. This is one basis for the phenomenon of hormesis, wherein a little damage applied regularly results in a better, longer lasting biological system: the HSPs are overcompensating.

Since aging is an accumulation of biochemical damage - or, looked at another way, all forms of unrepaired damage lead to loss of function and degeneration - we would expect that greater HSP activity translates into longer lives and a more more robust, resiliant biochemistry. This seems to be the case in laboratory animals:

Heat-shock proteins (Hsps) are increasingly being implicated in aging phenotypes and control of life span across species. They are targets of the conserved heat-shock factor and insulin/IGF1-like signaling pathways that affect life span and aging phenotypes. Hsps are expressed in tissue-specific and disease-specific patterns during aging, and their level of expression and induction by stress correlates with and, in some instances, predicts life span. In model organisms, Hsps have been shown to increase life span and ameliorate aging-associated proteotoxicity. Finally, Hsps have emerged as key components in regulating aging-related cellular phenotypes, including cell senescence, apoptosis and cancer. The Hsps, therefore, provide a metric of individual stress and aging and are potential targets for interventions in aging and aging-related diseases.

Both exercise and calorie restriction (CR) are forms of mild stress that temporarily enhance HSP activity, and it is plausible that boosted HSP activity contributes to the health and longevity benefits produced by regular exercise or cutting down calories whilst still obtaining optimal levels of nutrients in the diet. People who exercise or eat less have more effective self-repair systems, in other words. Along those lines, here is a recent paper looking at the biochemistry of exercise:

The study of the exercise-induced production of HSPs in skeletal muscle is important for the exercise scientist as it may provide a valuable insight into the molecular mechanisms by which regular exercise can provide increased protection against related and non-related stressors ... Data indicate that acute endurance- and resistance-type exercise protocols increase the muscle content of [various HSPs]. Although increased HSP transcription occurs during exercise, immediately post-exercise or several hours following exercise, time-course studies using western blotting techniques have typically demonstrated a significant increase in protein content is only detectable within 1-2 days following the exercise stress.


Following 'non-damaging' endurance-type activities (exercise that induces no overt structural and functional damage to the muscle), the stress response is thought to be mediated by redox signalling (transient and reversible oxidation of muscle proteins) as opposed to increases in contracting muscle temperature per se. Following 'damaging' forms of exercise (exercise that induces overt structural and functional damage to the muscle), the stress response is likely initiated by mechanical damage to protein structure and further augmented by the secondary damage associated with inflammatory processes occurring several days following the initial insult.

Exercise training induces an increase in baseline HSP levels, which is dependent on a sustained and currently unknown dose of training and also on the individual's initial training status. Furthermore, trained subjects display an attenuated or abolished stress response to customary exercise challenges, likely due to adaptations of baseline HSP levels and the antioxidant system.


As a non-pharmacological intervention, exercise and the associated up-regulation of HSPs and the possible correction of maladapted pathways may therefore prove effective in providing protection against protein misfolding diseases and in preserving muscle function during aging.

It is interesting that ongoing exercise in the form of a training program actually raises baseline HSP activity. You might compare that with present thinking on SIRT1 - that this sirtuin produces benefits in health and longevity by extending the period in which HSPs are more active following a triggering stress.

ResearchBlogging.orgMorton JP, Kayani AC, McArdle A, & Drust B (2009). The exercise-induced stress response of skeletal muscle, with specific emphasis on humans. Sports medicine (Auckland, N.Z.), 39 (8), 643-62 PMID: 19769414


Very interesting article, at any age it is highly advised to make exercise for different reasons, Exercise helps enhancing health in different ways like improving our respiratory system, our immune system, strengthens our heart, improving our circulation, etc. Thanks for this useful article on HSP's.

Posted by: Symposier at September 27th, 2009 9:49 PM

Since the induction of hsp70 is invoked by "high intensity" exercise, never by "low intensity" exercise (even after a duration of many hours), and since hsp70 levels continue for several days, could it be caused by a "switch". No studies seem to address the length of exercise needed to "trigger" a heat-shock response. It is my theory that even 5 minutes of 10 second sprinting and 20 second rest will be sufficient to trigger the heat-shock response. A study should be undertaken to determine the minimum high intensity(90%) exercise duration to elevate hsp70. It would be a critical factor in any exercise program for the elderly or sick.

Posted by: William McMillan at February 6th, 2014 3:20 AM

I do 4 by 4 HIIT training out of University of Norway. I get my heart rate to 85% of its maximum rate for 3 minutes and then seperated by an active recovery interval. I repeat this 4 times. Do I have to increase my percentage to 90% for HSPs to get turned on? I do this every other day.

Michael Gallo

Posted by: Michael Christopher Gallo at January 5th, 2020 3:30 PM
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