We’ve recently discussed evidence that resveratrol, a compound with some documented longevity-enhancing benefits in model organisms, might act by inducing the heat shock response. Heat shock proteins have been implicated in lifespan determination: Stochastic variations in heat shock protein expression have been invoked to explain variance in longevity between genetically identical organisms, with higher HSP expression associated with longer life.

It is therefore curious to learn that exercise, also thought to have a hormetic effect (i.e., acute stress now increases chronic stress tolerance later) downregulates expression of least one heat shock protein in elderly human subjects. From Simar et al.:

Physical Activity Modulates Heat Shock Protein-72 Expression and Limits Oxidative Damage Accumulation in a Healthy Elderly Population Aged 60–90 Years

Background. Reactive oxygen species production increases during aging, whereas protective mechanisms such as heat shock proteins (HSPs) or antioxidant capacity are depressed. Physical activity has been hypothesized to provide protection against oxidative damage during aging, but results remain controversial. This study aimed to investigate the effect of different levels of physical activity during aging on Hsp72 expression and systemic oxidative stress at rest and in response to maximal exercise.

Methods. Plasma antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC), thiobarbituric acid-reactive species (TBARS), advanced oxidized proteins products (AOPP), and Hsp72 expression in leukocytes were measured before and after maximal exercise testing in 32 elderly persons (aged 73.2 years), who were assigned to two different groups depending on their level of physical activity during the past 12 months (OLow = moderate to low level; OHigh = higher level).

Results. The OHigh group showed higher aerobic fitness and TEAC (both representing 120% of OLow values) as well as lower oxidative damage (50% of OLow values) and Hsp72 expression. Exercise led to a lower increase in oxidative damage in the OHigh group. Aerobic fitness was positively correlated with TEAC and negatively with lipid peroxidation (TBARS). Hsp72 expression was negatively correlated with TEAC but positively correlated with TBARS levels.

Conclusions. The key finding of this study is that, in people aged 60 to 90 years, long-term high level of physical activity preserved antioxidant capacity and limited oxidative damage accumulation. It also downregulated Hsp72 expression, an adaptation potentially resulting from lower levels of oxidative damage.

The authors’ explanation of the lowered Hsp72 levels — that lower overall oxidative damage results in an adaptive decrease in Hsp72 expression — is reasonable; Hsp72 is known to be involved in the cellular response to oxidative stress (e.g., in regulating peroxide-induced apoptosis). But what puzzles me is this: HSPs tend to be coordinately regulated, by elevated temperature or other sources of protein-folding stress. Does this finding suggest that all of the HSPs are lower in elderly patients who exercise? If so, what are the ramifications for the theory that chronically elevated HSPs are a key mechanism of resisting chronic low-level stress?