Polymorbidity, ageing of immune system and low-grade systemic inflammation: a challenge for modern medicine

Abstract

The review article considers the data from literature that concern polymorbidity aspects, its interrelations with ageing of immune system and lo-grade immune ageing, mechanisms of genesis, approaches to its prevention and treatment. Evolution of “comorbidity” and “polymorbidity” terms is traced, an updated definition of polymorbidity is proposed. The world-wide incidence of polymorbidity is increased and now it reaches 23-25% in general population, and up to 98%, in elderly people (> 65 years old). The risk factors of polymorbidity are considered, like as its social burden due to high costs for healthcare, high mortality rates, excessive treatment provided by multidisciplinary specialists. We present evidence for common molecular and cellular mechanisms involved in ageing and polymorbidity, being unified by the term “inflammaging” which represents a low-grade chronic systemic inflammation associated with ageing. The data are presented that concern the “inflammaging” development with involvement of ageing cells from innate and adaptive immunity systems, different pro and anti-inflammatory mediators, lifelong antigenic load. The data are analyzed concerning functional and structural changes in the inborn and adaptive immune system in ageing, role of these changes in “inflammaging” persistence and development of polymorbid conditions. There are complex interactions shown between the bodily senescence and immune ageing, with similar underlying mechanisms in some cases, however, being quite different in other instances. With age, upon existing risk factors, the changed adaptive immunity in most people is not able to full-scale coping with chronic antigenic load, thus increasing the risk of diseases. Moreover, in many elderly people these changes are compensated by steady activation of the innate immunity cells. It is noted that the aging events and development of disease (polymorbidity) cannot be considered distinct entities, since they can interact, being, however, basically different in their nature. In future, one should concentrate our efforts on elucidation of molecular and cellular mechanisms of these interactions, solution of the tasks oriented for development of such interventions that could be able to reduce harmful consequences of ageing and to use useful effects for health maintenance and reaching maximal longevity.