Frailty and Immunesenescence

The role played by the immune system in frailty is believed to be fundamental in the development and maintenance of a frailty state, but it remains mostly uncharacterised. The role of senescence and inflammageing has been discussed in detail earlier in Chap. 1 and in this chapter we shall focus on findings directly related to frailty.

Models

There has been little fundamental mechanistic research investigating the immune system in frailty in its truest sense. Therefore, it is necessary to consider models of frailty and draw conclusions where possible. Some of the models of frailty that have been utilised in research are discussed below.

Population based studies have demonstrated that the incidence of infection and subsequent mortality is higher in populations of frail people. Nursing homes represent a population where frailty can be assumed without direct measurement. The prevalence of pneumonia in a nursing home population is 30 times higher than the general population [39, 40]. Population based studies have identified that frailty is associated with inflammageing and immunesenescence [41-44]. As HIV could lead to the same characteristics of immunesenescence in older individuals, the identification of a subpopulation of HIV patients with frailty has led to comparison cohort studies between HIV patients with frailty and those without [45]. These studies focus upon the adaptive immune system and T cells in particular. Conversely, centenarians have been employed as a model of successful ageing [46,47].

Sarcopenia has been suggested as a human model of physical frailty. Sarcopenia as defined by EWGSOP is a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength with the risk of adverse outcomes such as physical disability, poor quality of life and death [48]. It is a more tangible concept than frailty and is easier to utilise in a research setting. Severe sarcopenia as defined by EWGSOP is considered pre-frailty as defined by the frailty phenotype. This suggests it could be either the physical component or a precursor to frailty. The prevalence of sarcopenia in frailty is unknown and this represents an important knowledge gap. However, the most common frailty phenotype parameters are slow gait speed and weakness which are also sarcopenia defining criteria [49].

Murine models have been developed to investigate sarcopenia and frailty using either cell signalling pathway knock out models or accelerated ageing models. Cell signalling pathway knock out models display changes in muscle fibre size, growth and the proportions of type 1 and 2 muscle fibres. In addition to these changes accelerated ageing models also display additional features of ageing such as osteoporosis and alopecia [50]. One murine model, the IL-10 knock out mouse, has been reported as a specific murine model of frailty [51] and a valid murine frailty index has been developed to improve murine frailty research [52]. These models offer an excellent and unique opportunity to study frailty in vivo but lack the sophistication and subtleties of frailty in humans.

 
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