Inflammaging: How our cytokines age us

08 May 2023

Inflammation is a natural biological response to tissue injury or infection, but chronic low-grade inflammation, also known as inflammaging, is a hallmark of ageing. In recent years, the relationship between cytokines, inflammation, and aging has become established.

Cytokines and Inflammation

Cytokines are small proteins that play a crucial role in cell signalling and communication. They are involved in various biological processes, including inflammation and aging. Inflammation is a protective response of the immune system to injury, infection, or irritation. Cytokines are released by immune cells and act as messengers to regulate the inflammatory response. They can either promote or inhibit inflammation, depending on the specific cytokine and the context in which it is released.

Inflammation is a complex process that involves the activation of immune cells, the release of cytokines, and the recruitment of additional immune cells to the site of injury or infection. Cytokines play a central role in this process by regulating the activation, proliferation, and differentiation of immune cells, as well as the production of other inflammatory mediators.

There are several types of cytokines involved in inflammation, including pro-inflammatory cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). Pro-inflammatory cytokines promote inflammation by stimulating the production of other inflammatory mediators, increasing vascular permeability, and recruiting immune cells to the site of injury or infection. In contrast, anti-inflammatory cytokines help to resolve inflammation by inhibiting the production of pro-inflammatory cytokines and promoting the clearance of inflammatory cells and debris.

Cytokines and Aging

During aging, there is a gradual decline in the function of the immune system, which is referred to as immunosenescence. This decline is associated with an increase in the production of pro-inflammatory cytokines, such as IL-6, TNF-α, and IL-1β. The chronic low-grade inflammation that occurs with aging is known as "inflammaging" and is thought to contribute to the development of age-related diseases, such as cardiovascular disease, diabetes, and neurodegenerative disorders.

Several factors contribute to the increased production of pro-inflammatory cytokines during aging, including cellular senescence, mitochondrial dysfunction, and changes in the composition of the gut microbiota. Cellular senescence is a state of irreversible cell cycle arrest that occurs in response to various stressors, such as DNA damage, oxidative stress, and telomere shortening. Senescent cells secrete a variety of pro-inflammatory cytokines, chemokines, and matrix metalloproteinases, which contribute to the chronic low-grade inflammation observed in aging.

Mitochondrial dysfunction is another factor that contributes to inflammaging. Mitochondria are the primary source of reactive oxygen species (ROS) in cells, and their function declines with age, leading to increased ROS production and oxidative stress. This, in turn, can activate the production of pro-inflammatory cytokines and promote inflammation.

Finally, changes in the composition of the gut microbiota during aging can also contribute to the increased production of pro-inflammatory cytokines. The gut microbiota plays a crucial role in maintaining immune homeostasis, and alterations in its composition have been associated with increased intestinal permeability, systemic inflammation, and the development of age-related diseases.

Therapeutic Strategies Targeting Cytokines

Given the central role of cytokines in inflammation and aging, targeting cytokines and their signaling pathways may provide potential therapeutic strategies for managing inflammation and age-related disorders. Several approaches have been investigated, including the use of cytokine inhibitors, receptor antagonists, and monoclonal antibodies.

For example, blocking the action of IL-6 or TNF-α has been shown to reduce inflammation and improve health outcomes in animal models and human clinical trials. In a study by Ershler and Keller, they discussed the age-associated increase in IL-6 gene expression and its potential role in late-life diseases and frailty. Dinarello's research on interleukin-18 (IL-18) also highlighted its involvement in the pathogenesis of inflammatory diseases.

Another approach is to enhance the production of anti-inflammatory cytokines, such as IL-10 and TGF-β, which can help to resolve inflammation and promote tissue repair. This can be achieved through the use of recombinant cytokines, gene therapy, or the modulation of endogenous cytokine production using pharmacological agents or dietary interventions.

The increase in pro-inflammatory cytokines during aging contributes to chronic low-grade inflammation, which is associated with various age-related diseases. Targeting cytokines and their signaling pathways may provide potential therapeutic strategies for managing inflammation and age-related disorders. Further research will increase our understanding of the complex interplay between cytokines, inflammation, and aging, and to develop novel interventions that can promote healthy aging.

IMAGE Kidney inlfammation