Elsevier

Clinical Nutrition

Volume 26, Issue 5, October 2007, Pages 524-534
Clinical Nutrition

Review
The role of hormones, cytokines and heat shock proteins during age-related muscle loss

https://doi.org/10.1016/j.clnu.2007.05.005Get rights and content

Summary

Ageing is associated with a progressive decline of muscle mass, strength, and quality, a condition known as sarcopenia. Due to the progressive ageing of western populations, age-related sarcopenia is a major public health problem. Several possible mechanisms for age-related muscle atrophy have been described; however the precise contribution of each is unknown. Age-related muscle loss is thought to be a multi-factoral process composed of events such as physical activity, nutritional intake, oxidative stress, inflammatory insults and hormonal changes. There is a need for a greater understanding of the loss of muscle mass with age as this could have a dramatic impact on the elderly and critically ill if this research leads to maintenance or improvement in functional ability. This review aims to outline the process of skeletal muscle degeneration with ageing, normal and aberrant skeletal muscle regeneration, and to address recent research on the effects of gender and sex steroid hormones during the process of age-related muscle loss.

Introduction

Ageing is associated with a progressive decline of muscle mass, strength, and quality, a condition known as the sarcopenia of ageing.1 Sarcopenia is associated with a decrease in functional performance, a greater risk of falls in the aged,1, 2 increased mobility disability3 and reduced energy needs.4 In addition, reduced muscle mass in aged individuals has been associated with decreased survival rates following critical illness.5 Estimates of the prevalence of sarcopenia range from 13% to 24% in adults over 60 years of age to more than 50% in persons aged 80 and older.2, 3, 4 Furthermore, the prevalence of age-related muscle loss is expected to dramatically increase, due to the progressive ageing of western populations.

Several possible mechanisms for age-related muscle atrophy have been described; however the precise contribution of each is unknown. Age-related muscle loss is thought to be a multi-factoral process composed of events such as physical activity, nutritional intake, oxidative stress, inflammatory insults and hormonal changes.6, 7, 8 In addition mitochondrial dysfunction may contribute to the development of sarcopenia, however this has been a subject of contentious debate and will not be discussed here, for a recent review on this subject see Dirks et al.9 The specific contribution of each of these factors is unknown but there is emerging evidence that the loss of gonadal hormones with age may be an important feature in the progression of sarcopenia. Gallagher et al. found that gender influenced muscle mass and determined that, with age, there was almost twice the reduction in muscle mass in males than in women.10 Factors such as testosterone levels, physical activity, cardiovascular disease and insulin-like growth factor-1 (IGF-1) have been shown to be significant predictors of muscle mass in men, and total fat mass and physical activity were significantly associated with muscle mass in women.6

There is a need for a greater understanding of the loss of muscle mass with age as this could have a dramatic impact on the elderly if this research leads to maintenance or improvement in functional ability. The majority of the literature presented here is mouse based, however the mechanisms of mouse muscle loss are similar to those in humans.11 The benefit of using animal studies eliminates secondary effects of disease caused by old age. This review aims to outline the process of skeletal muscle degeneration with ageing, normal and aberrant skeletal muscle regeneration, and to address recent research on the effects of gender and sex steroid hormones during the process of age-related muscle loss.

Section snippets

Skeletal muscle ageing

Muscle wasting and loss of skeletal muscle strength are inevitable concomitants of ageing and result from the loss of muscle fibres and atrophy of the remaining fibres as described in Fig. 1. By the age of 70 years, the cross-sectional area of skeletal muscle is reduced by up to 25–30%. Strength is reduced by 30–40%,12 and this continues to fall by 1–2% per year.13 Muscles of older individuals are also more susceptible to damage and recover poorly following damage.12, 14, 15, 16

One mechanism of

Does gender protect against age-related muscle loss?

In the developed world, most women live one-third of their lives in a state of profound estrogenic deprivation.94 In addition, with advancing age of women there is a decrease in the serum levels of testosterone and androgens.95 Moreover, elderly males have altered local levels of bioactive estrogens, secondary to reduced secretion of adrenal sex-steriod precursors to estrogen by aromatisation.96 Concentrations of other sex steroids in serum from men decline progressively with age, due to

Conclusions

Age-related sarcopenia is a major public health problem in the rapidly expanding elderly population. There is a need for a better understanding of the biological mechanisms and pathophysiology of sarcopenia as this may result in the development of therapeutic or preventative measures to address this problem. Ageing is associated with reduced levels of steroid hormones and this review has highlighted several differences between males and females with regard to age-related muscle loss and

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