Virtual Workshop: Inflammaging and Regeneration: Pain or Partnership?

The immune system relies on acute inflammation to mitigate infections, clear damaged cells and initiate tissue healing. A transient painful inflammatory response is tightly linked to regeneration, and an appreciation of the significance of this interplay in translational research is rapidly increasing. Moreover, many of the mechanisms that link inflammation to regeneration are rendered dysfunctional by the aging process. The progressive accumulation of senescent cells over time fosters a chronic milieu of inflammation termed “inflammaging”, leading to poor tissue repair and degenerative disease.

Age-related changes in immunity are characterized by a combination of adaptive immunity impairment and a persistent inflammatory response, which contribute to the progression of age-associated diseases that drives the aging process. Moreover, acute inflammatory responses to pathogens may be weakened in aging, leading to increased susceptibility to infection. We have an incomplete picture of the hierarchies in immune determinants that orchestrate effective tissue regeneration, and the divergent immune phenotypes that derail these processes.

This Workshop will bring together experts in two communities –immunology and regeneration — to explore the mechanisms underlying immune-mediated tissue turnover, adaptation and repair, and the complex remodeling of the immune system associated with aging. We will focus on the paradoxical need for transient inflammation in the regenerative process and co-existence of chronic inflammation and immunodeficiency that accompanies tissue senescence; the cellular and molecular cascades that allow responding cells to proliferate and either induce healthy healing or cause scarring; the age-related changes in macrophage polarization dynamics and adaptive immune responses that drive immune and stromal cells to both initiate and terminate healing responses; and the potential to target the regenerative functions that go awry with immunomodulators and senolytics. Designing interventions for therapeutic purposes is particularly challenging in the setting of aging, where homeostatic replacement of healthy tissue has been distorted, requiring a synergy of immunology and regenerative biology disciplines and approaches.

Published Information from the Workshop

• A Meeting report was written by Ludovic Gaut, Laura Muraine and was published on the Node in August 2021.