Abstract
Frailty is a common negative consequence of ageing. Sarcopenia, the syndrome of loss of muscle mass, quality and strength, is more common in older adults and has been considered a precursor syndrome or the physical manifestation of frailty. The pathophysiology of both syndromes is incompletely described with multiple causes, inter-relationships and complex pathways proposed. Age-associated changes to the immune system (both immunesenescence, the decline in immune function with ageing, and inflammageing, a state of chronic inflammation) have been suggested as contributors to sarcopenia and frailty but a direct causative role remains to be established. Frailty, sarcopenia and immunesenescence are commonly described in older adults but are not ubiquitous to ageing. There is evidence that all three conditions are reversible and all three appear to share common inflammatory drivers. It is unclear whether frailty, sarcopenia and immunesenescence are separate entities that co-occur due to coincidental or potentially confounding factors, or whether they are more intimately linked by the same underlying cellular mechanisms. This review explores these possibilities focusing on innate immunity, and in particular associations with neutrophil dysfunction, inflammation and known mechanisms described to date. Furthermore, we consider whether the age-related decline in immune cell function (such as neutrophil migration), increased inflammation and the dysregulation of the phosphoinositide 3-kinase (PI3K)-Akt pathway in neutrophils could contribute pathogenically to sarcopenia and frailty.
Highlights
MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, B15 2WD, UK article info
We consider whether the age-related decline in immune cell function, increased inflammation and the dysregulation of the phosphoinositide 3-kinase (PI3K)-Akt pathway in neutrophils could contribute pathogenically to sarcopenia and frailty
Sarcopenia is better understood than frailty largely due to its effects being concentrated on a single system, the neuromuscular system, and for this reason it has been suggested as a physical model of frailty
Summary
Sarcopenia can be considered as one of the main physical drivers of frailty or perhaps even a precursor state if it is present without a medical classification of frailty as described above. The diversity in the cut offs, in defining low muscle mass, utilised in research has led to huge disparity in the prevalence of reported low muscle mass with prevalence reported as between 3.3 to 41.5% in community populations over 65 (von Haehling et al, 2010). This has been recognised by the EWGSOP who have recommended that more research is urgently needed in order to obtain good reference values for populations around the world. A more inclusive definition of sarcopenia may incorporate the loss of muscle mass, reduced muscle quality and a loss of functional strength, as shown in Fig. 1, which depicts age-related changes occurring within the muscle from the whole muscle level through to a cellular level and how these contribute to the loss of muscle mass, quality, strength and power
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