A review of epigenetics and its association with ageing of muscle and bone.

Ageing is defined as the 'increasing frailty of an organism with time that reduces the ability of that organism to deal with stress'. It has been suggested that epigenetics may underlie the observation that some individuals appear to age faster than others. Epigenetics is the study of changes which occur in an organism due to changes in expression of the genetic code rather than changes to the genetic code itself; that is, epigenetic mechanisms impact upon the function of DNA without changing the DNA sequence. It is important to recognise that epigenetic changes, in contrast to genetic changes, can vary according to different cell types and therefore can demonstrate significant tissue-specificity. There are different types of epigenetic mechanisms: histone modification, non-coding RNAs and DNA methylation. Epigenetic clocks have been developed using statistical techniques to identify the optimal combination of CpG sites (from methylation arrays) to correlate with chronological age. This review considers how epigenetic factors may affect rates of ageing of muscle and bone and provides an overview of current understanding in this area. We discuss studies using first-generation epigenetic clocks, as well as the second-generation iterations, which appear to show stronger associations with the ageing muscle phenotype. We also review epigenome-wide association studies that have been performed in various tissues examining relationships with osteoporosis and fracture. It is hoped that an understanding of this area will lead to interventions that might prevent or reduce rates of musculoskeletal ageing in later life.

A pas de deux of osteoporosis and sarcopenia: osteosarcopenia.

The musculoskeletal conditions osteoporosis and sarcopenia are highly prevalent in older adults. Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone, whereas sarcopenia is identified by the loss of muscle strength, function and mass. Osteoporosis represents a major health problem contributing to millions of fractures worldwide on an annual basis, whereas sarcopenia is associated with a range of adverse physical and metabolic outcomes. They both affect physical and social function, confidence and quality of life as well as contributing to high health-care costs worldwide. Osteosarcopenia is the term given when both conditions occur concomitantly and it has been suggested that interactions between these two conditions may accelerate individual disease progression as co-existence of osteoporosis and sarcopenia is associated with higher morbidity from falls, fracture, disability as well as mortality. In this review, we will outline the epidemiology, pathogenesis and clinical consequences of osteosarcopenia and discuss available management strategies.

Pathophysiology and treatment of osteoporosis: challenges for clinical practice in older people.

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people.