Inflammaging is a low degree of chronic and systemic tissue inflammation associated with aging, and is intimately linked to pro-inflammatory mediators. These substances are involved in the pathogenesis of chronic inflammatory diseases and related psychopathological symptoms. Aging and inflammation have been defined in their interplay since the 1991 New York Academy of Sciences conference by a group of researchers. It ihas been suggested that biological, chemical, and physics damage led to a chronic inflammatory process. The link between the molecular and cellular balance capable of permitting a physiological healthy aging or a cognitive impairment is still unclear. The innate immune system plays a crucial role in the inflammatory processes, usually reduced at advanced ages. In the elderly, senescent microglia augment the production of proinflammatory mediators with reduced chemotaxis and phagocytosis capacities, particularly of amyloid-β fibrils. The raised systemic inflammatory state and peripheral immunosenescence interfere with neuronal immune cell activity and reactivity.
In recent decades there has been a progressive increase in the prevalence of chronic diseases, mainly due to an ever-increasing life expectancy. Aging and chronic diseases find their fil rouge in chronic inflammation.
Aging and inflammation have been defined in their interplay since the 1991 New York Academy of Sciences conference by a group of researchers [1]. Among these, Claudio Franceschi conceptualized the word "inflammaging". He and his group elaborated that a constantly growing survival together with the aging process affected by a biological, chemical, and physics damage led to a chronic inflammatory process. Longevity is a characteristic of modern industrialized society, and successful aging is the key to countering destructive processes due to several causes and contributing to organ damage. Franceschi et al. also speculated a series of defensive systems against chronic inflammatory injuries in the elderly, called "anti-inflammaging". They evaluated centenarians who were able to escape the diseases typical of advanced ages. These kinds of subjects were defined as "escapers" [2][3].
Although different tissues and organs are usually targeted by long-term inflammation, one of the most sensitive due to its limited renewal capacity is the brain. Neurodegenerative diseases are a direct consequence. The link between the molecular and cellular balance capable of permitting a physiological healthy aging or a cognitive impairment is still unclear.
The actual models suggest that exposure during lifespan to several exogenous and endogenous insults triggers an immune response, inducing a state of chronic physiological inflammation that is protective for long-term survival at certain levels. As mentioned above, a systemic inflammatory state defines a phenotype typical of successful aging. Also, neurodegeneration is affected by an age-related increase in inflammation, with simultaneous adaptive activation of anti-inflammation procedures [4].
The innate immune system plays a crucial role in the inflammatory processes, usually reduced at advanced ages. Sometimes, also hyperreactivity could be age-associated. Microglia are main actors among the resident immune cells in the brain. In the elderly, senescent microglia augment the production of proinflammatory mediators with reduced chemotaxis and phagocytosis capacities, particularly of amyloid-β fibrils [5]. Geriatric microglia amass mitochondrial DNA with detrimental effects on cells leading to ROS accumulation and sustaining further damages.
Also, the reduced effectiveness of the adaptive immune system contributes to declined immune response versus biological threats [6].
The raised systemic inflammatory state and peripheral immunosenescence interfere with neuronal immune cell activity and reactivity. The consequence is a chronic low-grade inflammatory condition called neuro-inflammaging. The activated glia in a loop sustained by cytokines, oxidative stress, and damage is mainly involved in memory loss and cognitive decline. Immunosenescence and inflammaging induce brain suffering, with the subsequent spread of clinical psychological signs and symptoms such as cognitive impairment, behavior alteration, or mental disorders [7].
This pervasive process of aging, known as "inflammaging", is characterized by a low degree of chronic and systemic tissue inflammation, revealed by high levels of some biomarkers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFa) [1]. Growing evidence has drawn attention to the potential role of these and other inflammatory mediators in the pathogenesis of chronic inflammatory diseases and related psychopathological symptoms, such as depression, anxiety, and alexithymia as pervasive and worsening symptoms and signs of the organic pathology. Chronic neuroinflammation plays a primary pathophysiological role in developing neurotoxic alterations of those brain regions involved in emotional regulation, contributing i.e. to the development of major depressive disorder (MDD) [8].
BThis review is based on the role of theis neuro-inflammatory process, this assessment focuses on in the connecrrelation between chronic inflammatory diseases commonly found in older individuals (known as typical of advanced ages (neuro-inflammaging) and psychopathological symptoms. The emphasis is on comprehe, with particular attention to understanding the immune-pathogenetic mechanisms involved and exploring the potential applicationuse of immunomodulatory drugs in addressingthe management of clinical psychological indicatorsigns [7].