Kevin J. Milne

Heat shock proteins and exercise: a primer.

Heat shock proteins (HSPs) are, in general, prosurvival molecules within the cellular environment, and the overexpression of even just 1 family of HSPs can lead to protection against and improvements after a variety of stressors. Not surprisingly, a fertile area of study has grown out of efforts to exploit the innate biologic behaviour of HSPs. Exercise, because of the inherent physiologic stresses associated with it, is but 1 stimulus that can result in a robust increase in various HSPs in several tissues, not the least of which happen to be the heart and skeletal muscle. The purpose of this review is to introduce the reader to the major HSP families, the control of their expression, and some of their biologic functions, specifically with respect to the influence of exercise. Moreover, as the first in a series of reviews from a common symposium, we will briefly introduce the concepts presented by the other authors, which include the effects of different exercise paradigms on skeletal muscle HSPs in the adult and aged systems, HSPs as regulators of inflammation, and the ion channel stabilizing effects of HSPs.

Sex and life expectancy.

BACKGROUND A sexual dimorphism in human life expectancy has existed in almost every country for as long as records have been kept. Although human life expectancy has increased each year, females still live longer, on average, than males. Undoubtedly, the reasons for the sex gap in life expectancy are multifaceted, and it has been discussed from both sociological and biological perspectives. However, even if biological factors make up only a small percentage of the determinants of the sex difference in this phenomenon, parity in average life expectancy should not be anticipated. OBJECTIVE The aim of this review is to highlight biological mechanisms that may underlie the sexual dimorphism in life expectancy. METHODS Using PubMed, ISI Web of Knowledge, and Google Scholar, as well as cited and citing reference histories of articles through August 2012, English-language articles were identified, read, and synthesized into categories that could account for biological sex differences in human life expectancy. RESULTS The examination of biological mechanisms accounting for the female-based advantage in human life expectancy has been an active area of inquiry; however, it is still difficult to prove the relative importance of any 1 factor. Nonetheless, biological differences between the sexes do exist and include differences in genetic and physiological factors such as progressive skewing of X chromosome inactivation, telomere attrition, mitochondrial inheritance, hormonal and cellular responses to stress, immune function, and metabolic substrate handling among others. These factors may account for at least a part of the female advantage in human life expectancy. CONCLUSIONS Despite noted gaps in sex equality, higher body fat percentages and lower physical activity levels globally at all ages, a sex-based gap in life expectancy exists in nearly every country for which data exist. There are several biological mechanisms that may contribute to explaining why females live longer than men on average, but the complexity of the human life experience makes research examining the contribution of any single factor for the female advantage difficult. However, this information may still prove important to the development of strategies for healthy aging in both sexes.

Response of the myocardium to exercise: sex-specific regulation of hsp70.

Sex is a potent modifier of the cardiovascular system because males and females differ in several aspects of the hearts biology and physiology. Epidemiologically, premenopausal women possess a distinct advantage over men in the occurrence of cardiovascular heart disease; however, this advantage shifts to men once a negative cardiac event has occurred. The reasons for these differences are not completely understood and are likely attributable to many factors. Nonetheless, the sex hormones seem to be important regulators of myocardial health. Of particular note, the sex hormones influence the molecular and physiological responses of the heart to the stress of exercise including the expression of several vital proteins such as the cardioprotective 70-kDa heat-shock protein, Hsp70. This review will focus on the exercise-induced expression of Hsp70 and how it is modified by sex. A better understanding of how sex, the sex hormones in particular, modifies the exercise stress response has important implications in the prescription of exercise to males and females, young or old.

Reductions in ambulatory blood pressure in young normotensive men and women after isometric resistance training and its relationship with cardiovascular reactivity.

Background There has been very little published work exploring the comparative effects of isometric resistance training (IRT) on blood pressure (BP) in men and women. Most of the previously published work has involved men and used resting BP as the primary outcome variable. Early evidence suggests that IRT is particularly effective in older women and has a positive influence on ambulatory BP, a better predictor of disease risk. Objectives With the WHO now placing global emphasis on the primary prevention of hypertension, the goals of this proof-of-concept study were to (i) examine whether sex differences exist in the ambulatory BP-lowering effects of IRT in young, normotensive men and women and (ii) determine whether these reductions can be predicted by simple laboratory stress tasks (a 2-min sustained isometric contraction and a math task involving subtracting a two-digit number from a series of numbers). Results There were no differences in the IRT-induced reductions in 24-h (men: &Dgr;4 mmHg, women: &Dgr;4 mmHg), daytime (men: &Dgr;3 mmHg, women: &Dgr;4 mmHg), or night-time (men: &Dgr;4 mmHg, women: &Dgr;3 mmHg) ambulatory BP in men (n=13) and women (n=11) (P<0.05) and these changes were not associated with systolic BP reactivity to either stress task (all P>0.05). Conclusion Our data suggest that lower ambulatory BP can be achieved, to a similar magnitude in young healthy women as well as men, with IRT; however, the BP-lowering effectiveness cannot be predicted by systolic BP reactivity. Taken together, this work heralds a potentially novel approach to the primary prevention of hypertension in both men and women and warrants further investigation in a larger clinical outcome trial.

HSP, Exercise and Skeletal Muscle

Skeletal muscle, which represents about 40% of the body mass in man, is an integrated organ, which possesses an extensive blood supply and innervations to support groups of muscles and muscle fibers (motor units) which must respond to a wide range of activities. Over the lifespan, skeletal muscle is forced to adapt to a variety of influences including growth and development, aging, hormonal influences, and changes in activity level. In this regard, skeletal muscle expresses the evolutionarily conserved group of proteins known as heat shock proteins (HSP) which may be critical to this adaptive process. Indeed the induction of HSP by the physiologically relevant stimulus of exercise may be harnessed as a means of protecting skeletal muscle and it’s components against a variety of insults. These proteins may also be important in chaperoning muscle remodeling. The following review addresses these issues while simultaneously revealing the paucity of information available on this subject in such an important organ

Acute Response to a 2-Minute Isometric Exercise Test Predicts the Blood Pressure-Lowering Efficacy of Isometric Resistance Training in Young Adults

BACKGROUND This work aimed to explore whether different forms of a simple isometric exercise test could be used to predict the blood pressure (BP)-lowering efficacy of different types of isometric resistance training (IRT) in healthy young adults. In light of the emphasis on primary prevention of hypertension, identifying those with normal BP who will respond to IRT is important. Also, heightened BP reactivity increases hypertension risk, and as IRT reduces BP reactivity in patients with hypertension, it warrants further investigation in a healthy population. METHODS Forty-six young men and women (24 ± 5 years; 116 ± 10/ 68 ± 8 mm Hg) were recruited from 2 study sites: Windsor, Canada (n = 26; 13 women), and Northampton, United Kingdom (n = 20; 10 women). Resting BP and BP reactivity to an isometric exercise test were assessed prior to and following 10 weeks of thrice weekly IRT. Canadian participants trained on a handgrip dynamometer (isometric handgrip, IHG), while participants in the UK trained on an isometric leg extension dynamometer (ILE). RESULTS Men and women enrolled in both interventions demonstrated significant reductions in systolic BP (P < 0.001) and pulse pressure (P < 0.05). Additionally, test-induced systolic BP changes to IHG and ILE tests were associated with IHG and ILE training-induced reductions in systolic BP after 10 weeks of training, respectively (r = 0.58 and r = 0.77; for IHG and ILE; P < 0.05). CONCLUSIONS The acute BP response to an isometric exercise test appears to be a viable tool to identify individuals who may respond to traditional IRT prescription.