Inflammation, coagulation, and the pathway to frailty

Abstract

There are inevitable physiologic changes associated with advancing age, yet for some people these changes are exaggerated, and as a result a phenotype emerges recognized as "frailty." Why some people become frail and others do not remains incompletely understood. Although chronic illnesses are common among frail elderly persons, some will develop all of the phenotypic features without a diagnosed underlying disease. It has been recognized that certain proinflammatory cytokines and coagulation factors are elevated to a greater extent in those who are frail than in age-matched nonfrail individuals. In this review, we provide an overview of current research in the biology of frailty with particular emphasis on the role of inflammatory pathways and disordered coagulation in its pathogenesis.

Figure

Pathway to frailty. Proinflammatory signals, including IL-6 and TNF-α, increase with age, as do markers of activated coagulation, including D-dimer, fibrinogen, PAI, and Factor VIII. To the extent that these are primary processes, they may contribute to a cycle of physiologic changes that, in composite, are described as “frailty.”