Muscle mapping over lifespan reveals patterns of female ageing

A first-time look at female muscle health over the decades has revealed the critical period in mid-life when women’s physical activity, particularly strength-based exercise, needs to increase, not slow down.

Described across two articles published in the Journal of Physiology (links below), the research by Deakin University’s Institute for Physical Activity and Nutrition (IPAN) provides the clearest picture yet of the role played by the female sex hormones oestrogen and progesterone in muscle ageing, especially during the menopausal transition.

Professor Severine Lamon, an Australian Research Council Future Fellow and co-director (Victoria) of the Centre for Sex and Gender Equity in Health and Medical Research, said the research shows that fluctuations in female sex hormones across the lifespan should be considered when developing therapies to mitigate age-related muscle wasting and improve the female health span.

‘Females live longer than males, but they experience worse health and disability in the later decades of life, so there is an urgent need to study female-specific patterns of ageing,’ Professor Lamon said.

‘Our findings show a clear acceleration of muscle ageing when women are in their 40s, 50s and 60s and undergoing the menopausal transition. In younger women, but also in men, age-related muscle decline happens gradually. In middle-aged women, however, many indicators of muscle health display a sudden and sharp decline that coincides with the onset of menopause, when the ovaries stop producing female sex hormones.’

The study mapped female body composition, muscle mass, muscle function, the architecture of the muscle cell, and gene expression in 100 women aged between 18 and 80 and examined the relationships with circulating sex hormones.

This information has enabled the research team to precisely describe the trajectory of female muscle ageing on multiple levels, from what is visible from the outside to what is happening inside the muscle cells, and how these changes are influenced by the presence of oestrogen and progesterone in the body.

‘We now have a better understanding of the way oestrogen and progesterone contribute to muscle mass and muscle cell structure across the female lifespan,’ Professor Lamon said.

‘These results suggest that maintaining higher levels of female hormones in the system for longer, for example through hormone replacement therapy, might be beneficial for muscle ageing.

‘A unique strength of this study was how every measurement was tightly controlled for influential factors that may have confounded the results, including the phase of the menstrual cycle for premenopausal females, menopausal status, the intake of contraceptive hormones or hormone replacement therapy as well as sleep, dietary intake and physical activity,’ Professor Lamon said.

As part of the study, PhD candidate Annabel Critchlow also discovered unique patterns of gene expression in female muscle across ageing.

Ms Critchlow collected a small piece of muscle tissue from each participant, approximately the size of a grain of rice, and looked at how genes are being turned on or off in muscle during ageing.

She found that genes related to the mitochondrial function, which is responsible for energy production in the cell, consistently decreased with ageing. Processes responsible for degrading damaged proteins in the cells were also suppressed in the later decades, potentially causing further damage to the cell and leading to a loss of muscle mass and quality.

Why muscle strength matters more after 40

‘This study reinforces an important message that maintaining muscle mass and function at all ages is vitally important for healthy ageing,’ Ms Critchlow said.

‘It also highlights that there is a critical period starting in the mid-40s when women are at heightened risk of rapidly losing muscle mass and function. This is when women need to start focusing on exercises that build body strength to slow down muscle ageing in coming decades.

‘While we have long understood that males and females age differently, current interventions and therapies to delay or combat musculoskeletal ageing are almost always based on what is known about the male body, simply because the equivalent data has not been available in females. Studying both sexes increases the efficacy of medical and lifestyle interventions for all,’ Ms Critchlow said.