In the year 2000 the group lead by Franceschi coined the term ‘Inflamm-aging‘ to refer to a low grade pro-inflammatory status that appears in the process of aging. Machrofages, cellular stress and genetic factors play an important role in its production. It has also been hypothesized that this inflammatory environment can predispose the organism to the development of a series age-related diseases.

The presence of a pro-inflammatory phenotype in mammals is linked to an increased gene expression connected to inflammation and to the immune response in tissues, with an increase of cytochines levels in serum, such as IL-6 and TNF- α and with the activation of the NF-KB that is the main regulator of the inflammatory response.

The systemic inflammation linked to inflammaging can for instance worsen vascular pathologies and cause arteriosclerosis.

Cortisol is a powerful anti-inflammatory agent although it induces protein catabolism, for instance in muscle tissue, and bone resorption.

Chronic inflammation also influences insulin resistance in muscles and in adipose tissue and interferes with the energy homeostasis and the functions that regulate cell survival.

Inflammaging induces the anti-inflammaging action of cortisol and induces insulin resistance,  a condition in which the liver is not able to respond to the insulin stimulus aimed at stopping the production of hormone-binding proteins. This condition leads to excess hepatic production of these proteins, among which cortisol binding globulin, which in turn causes the inactivation of cortisol and the nullification of the anti-inflammaging process because of the paradoxical coexistence of immunodeficiency and inflammation. The phenomenon of anti-inflammaging, mainly exerted by cortisol, with the passage of time becomes the cause of a marked decline of immunological functions. The coexistence with the increased levels of proinflammatory cytokines (inflammaging), has a negative impact on metabolism, bone density, strength, exercise tolerance, the vascular system, cognitive function, and mood. Inflammaging could be thus considered as an autoimmune syndrome that acts against the innate immune system and the imbalance between inflammaging and anti-inflammaging as an imbalance between the innate immune system and the adaptive one.

This accumulation of cortisol is also responsible for many complications related to old age (sarcopenia, osteoporosis, metabolic syndrome, diabetes, overweight, neurodegeneration and immunodepression).