Inflammation and aging: signaling pathways and intervention therapies

Abstract

Aging is characterized by systemic chronic inflammation, which is accompanied by cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. Given the multidimensional complexity of aging, there is an urgent need for a systematic organization of inflammaging through dimensionality reduction. Factors secreted by senescent cells, known as the senescence-associated secretory phenotype (SASP), promote chronic inflammation and can induce senescence in normal cells. At the same time, chronic inflammation accelerates the senescence of immune cells, resulting in weakened immune function and an inability to clear senescent cells and inflammatory factors, which creates a vicious cycle of inflammation and senescence. Persistently elevated inflammation levels in organs such as the bone marrow, liver, and lungs cannot be eliminated in time, leading to organ damage and aging-related diseases. Therefore, inflammation has been recognized as an endogenous factor in aging, and the elimination of inflammation could be a potential strategy for anti-aging. Here we discuss inflammaging at the molecular, cellular, organ, and disease levels, and review current aging models, the implications of cutting-edge single cell technologies, as well as anti-aging strategies. Since preventing and alleviating aging-related diseases and improving the overall quality of life are the ultimate goals of aging research, our review highlights the critical features and potential mechanisms of inflammation and aging, along with the latest developments and future directions in aging research, providing a theoretical foundation for novel and practical anti-aging strategies.

Fig. 1

Inflammaging at the molecular, cellular, and organ levels. During the aging process, almost all cells in the body undergo senescence, a state characterized by a dysfunctional state and senescence-associated secretory phenotype (SASP). While immune cells play a crucial role in recognizing and eliminating these senescent cells, they are also affected by SASP, leading to a phenomenon called immunosenescence. Immunosenescence can impair the immunity to respond to infections and diseases, making the organism more vulnerable to illnesses. Moreover, the accumulation of senescent cells can trigger inflammation in organs, leading to organ damage and an increased risk of age-related diseases. This process is exacerbated by positive feedback loops that drive the accumulation of inflammation and organ damage, leading to further inflammation and an even higher risk of aging-related diseases

Fig. 2

Characterization of HSC differentiation into immune cells during aging. Inflammation in senescent bone marrow impairs the function of HSCs. HSCs differentiate into various immune cells, and their senescence leads to changes in the number and functions of immune cells. Common features of immune cell senescence include a decline in performing immune functions and an increase in the release of inflammatory factors

Fig. 3

Aging-organ atlas. Aging manifests as a decline in organ function and an increased susceptibility to diseases. Organs are mainly divided into immune organs, sterile organ, and others. Functional changes in cells are shown in each organ

Fig. 4

Schematic diagram of six inflammatory cell death molecular patterns. The source of inflammation comes from cell death in addition to the release of SASP from senescent cells. Both immune response-mediated and damage signaling-mediated cell death promote inflammation to some extent. Various modes of cell death (in addition to apoptosis) release large amounts of inflammatory factors