Inflammaging: The Next Challenge-Exploring the Role of Gut Microbiota, Environmental Factors, and Sex Differences

Abstract

The term 'inflammaging' has been coined to describe the chronic state of inflammation derived from ongoing cycles of tissue damage and the subsequent immune responses. This inflammatory status contributes to the decline of organs and physiological functions, accelerates the aging process, and increases the risk of age-related illnesses and death. During aging, the gut microbiota (GM) undergoes significant changes, including a decreased diversity of species, a decline in beneficial bacteria, and a rise in proinflammatory ones, resulting in persistent low-grade inflammation. Moreover, environmental factors, such as diet and medications, contribute to age-related changes in GM and immune function, preventing or promoting inflammaging. This narrative review aims to clarify the underlying mechanisms of inflammaging and to specifically investigate the influence of GM and several environmental factors on these mechanisms, while also exploring potential differences related to sex. Moreover, lifestyle and pharmacological interventions will be suggested to promote healthy aging.

Keywords: aging; diet; gut microbiota; immunosenescence; inflammation; sex differences.

Figure 1

Immunosenescence, characterized by thymic involution, a reduction in hematopoietic stem cells, and decreased humoral immune response, leads to inflammaging. This condition results in the production of proinflammatory cytokines, oxidative stress, DNA instability, and the senescence-associated secretory phenotype (SASP). In turn, inflammaging is influenced by sex, environmental factors, and the dysbiosis of the gut microbiota (GM), which is characterized by increased levels of lipopolysaccharide (LPS), increased mucosa permeability, decreased gut cell autophagy, and an alteration in bile acid metabolism.