Fig. 1. Cellular and molecular components of inflammageing.

Low-grade chronic systemic inflammation, or inflammageing, comprises multiple inflammatory factors that originate from various cellular sources in aged organisms. Aged pro-inflammatory tissue macrophages produce cytokines and chemokines¹⁶⁸, and senescent cells secrete a plethora of pro-inflammatory components and matrix metalloproteinases (MMPs) as components of the senescence-associated secretory phenotype^113,114. Moreover, non-immune cells, such as adipocytes, preadipocytes and stromal cells (including fibroblasts and endothelial cells), contribute to inflammageing by secreting soluble inflammatory factors and altering the tissue microarchitecture of aged organs⁷. The pro-inflammatory chemokines drive excessive immune cell infiltration in tissues, where the cytokines (such as IL-6 and IL-1β) and immunoregulatory factors (such as prostaglandin E₂ (PGE₂)) reprogramme immune cell subsets to a more pro-inflammatory and dysfunctional state^169,170. In turn, the dysfunctional immune cells, including macrophages and T cells, amplify the inflammatory and destructive processes in ageing tissues^169,171,172. This crosstalk between cellular and molecular components of inflammageing ultimately results in a progressive functional decline in various organs and leads to age-associated diseases. CCL, CC-chemokine ligand; CXCL, CXC-chemokine ligand; GDF15, growth/differentiation factor 15; IFNβ, interferon-β; TGFβ, transforming growth factor-β.