Insulin resistance, chronic inflammation and the link with immunosenescence

Abstract

Ageing is associated with an activation of the innate immune system which manifests in a chronic, low-grade, inflammatory status common in elderly individuals. Age-related inflammatory activity, as measured by increased serum levels of proinflammatory cytokines and activation of inflammatory signalling pathways, leads to long-term tissue damage and is thought to contribute to- and occur as a consequence of-immunosenescence. In addition to immune system deregulation, this elevated inflammatory status is associated with a number of age-related diseases and conditions, including neurodegeneration, atherosclerosis, sarcopenia, and diabetes, and is a main contributor to the age-related decline in physical function and vitality known as frailty. Inflammation is also an important component of the insulin resistance syndrome. In addition to age, a major risk factor for the development of the insulin resistance syndrome is obesity. Obesity is associated with increased proinflammatory cytokine production and altered regulation of both pro and antiinflammatory molecules, including a class of adipose-derived signalling molecules termed adipocytokines. The increased production of inflammatory mol-ecules in obese and nonobese insulin resistant elderly individuals may contribute to age-related decline in health, including dysfunction of the immune system. Antiinflammatory strategies for the treatment of the insulin resistance syndrome may promote remodelling of the immune system thereby contributing to remediation of immunity and prevention of frailty in the elderly population.