Review
Inflammation markers predicting frailty and mortality in the elderly

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Abstract

Greater numbers of individuals are living to older ages. A major concern at both individual and population levels is how to live these years at a high functional level. If we had physiological markers to identify those at risk for progressive functional decline and impeding death, therapies could be targeted towards these individuals to prevent adverse outcomes. Senescence is presently considered as the consequence of lifelong antigenic stress impinging upon the individual genetic background. We might consider inflammation markers as synthetic measures of lifelong attrition combined with genetic tendency to develop an inflammatory phenotype. Such biomarkers are the most powerful predictors of frailty and mortality in the elderly available today. The aim of this review is to translate results from the research on ageing into a practical view, suggesting new tools for the clinical approach to older people.

Section snippets

Inflamm-ageing and inflammation markers

Ageing is characterized by a chronic, low-grade inflammatory status, the so-called “inflamm-ageing”, which is under genetic control and appears to be the consequence of lifelong antigenic load (Franceschi et al., 2000a, Franceschi et al., 2000b, Ginaldi and Sternberg, 2003, Ginaldi et al., 2005, Pawelec et al., 2005a). This peculiar inflammatory activity, leading to long-term tissue damage, is detrimental for longevity and has been found to be related to mortality risk from all causes in older

Serological markers of inflamm-ageing

Low-grade elevations in levels of circulating proinflammatory cytokines and their receptors, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, interleukin (IL)-1 receptor antagonist (IL-1Ra), soluble TNF receptors, etc., are strong independent risk factors of morbidity and mortality in the elderly (Bruunsgaard and Pedersen, 2003, Brunsgaard et al., 2003a). A further consequence of hyperproduction of proinflammatory cytokines in the elderly is the increased production of diverse

Cellular markers of inflamm-ageing

A recent observational study demonstrated that the white blood cell count, which is a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, is an important predictor of all-causes mortality in the elderly, mainly cardiovascular disease entities (Margolis et al., 2005). Moreover, a high leukocyte count may identify high-risk individuals who are not currently identified by traditional cardiovascular risk factors (Leng et al., 2005).

Concerning lymphocyte

Genetic markers of inflamm-ageing

Ageing is the product of an interaction among genetic, environmental and lifestyle factors, which in turn influence longevity (Cooper, 2003, Olivieri et al., 2003).

An inflammatory status is compatible with extreme longevity in good health and paradoxically proinflammatory characteristics have been documented in healthy centenarians (Franceschi and Bonafè, 2003, Franceschi et al., 2000a). From this perspective, inflammation and the proinflammatory status present in aged people and centenarians

The immune risk phenotype (IRP)

Senescence has been coined as the phase of the life span associated with an increased probability of dying. It has been also defined as a process resulting in an increased probability of death secondary to pathology (Boren and Gershwin, 2004). The immune risk phenotype (IRP) is a set of bioparameters associated with poor immune function predicting high-risk mortality in the elderly (Pawelec et al., 2005b). In the Swedish longitudinal study, known as the OCTO study (Ferguson et al., 1995),

Concluding remarks

Ageing rate and longevity, as well as the incidence of the great majority of age-related diseases, which represent the most frequent causes of mortality in the elderly, are determined by both environmental and genetic factors. Quality and quantity of the lifelong antigenic load, conditioning inflamm-ageing, are major determinants of immunosenescence, ageing rate and longevity, as well as of quality of life in advanced ages (De Martinis et al., 2005).

The analysis of immunological changes during

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