Inflammaging impairs peripheral nerve maintenance and regeneration

Abstract

The regenerative capacity of peripheral nerves declines during aging, contributing to the development of neuropathies, limiting organism function. Changes in Schwann cells prompt failures in instructing maintenance and regeneration of aging nerves; molecular mechanisms of which have yet to be delineated. Here, we identified an altered inflammatory environment leading to a defective Schwann cell response, as an underlying mechanism of impaired nerve regeneration during aging. Chronic inflammation was detected in intact uninjured old nerves, characterized by increased macrophage infiltration and raised levels of monocyte chemoattractant protein 1 (MCP1) and CC chemokine ligand 11 (CCL11). Schwann cells in the old nerves appeared partially dedifferentiated, accompanied by an activated repair program independent of injury. Upon sciatic nerve injury, an initial delayed immune response was followed by a persistent hyperinflammatory state accompanied by a diminished repair process. As a contributing factor to nerve aging, we showed that CCL11 interfered with Schwann cell differentiation in vitro and in vivo. Our results indicate that increased infiltration of macrophages and inflammatory signals diminish regenerative capacity of aging nerves by altering Schwann cell behavior. The study identifies CCL11 as a promising target for anti‐inflammatory therapies aiming to improve nerve regeneration in old age.

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

“…20 ANXA1 in innate and adaptive immune cells mediate the resolution of inflammation to induce protective effect, such alleviation of inflammation promoted peripheral nerve maintenance and regeneration. 5,42 However, some limitation existed in the current study, for the precise cellular resource of ANXA1 remains unknown, it will be verified in our future study.…”

Metformin improves cognition of aged mice by promoting cerebral angiogenesis and neurogenesis

“…This inhibitory action also induces an anti-inflammatory response by inhibiting proIL-1b production in macrophages [ 30 ]. Interestingly, anti-inflammatory therapies aiming to improve neurogenesis in old age and the inflammatory microenvironment of the aging brain regulate quiescence or activation of NSCs [ 34 , 35 ]. Meanwhile, we found that metformin treatment increased the extracellular acidification rate (ECAR), even when oxidative phosphorylation-dependent ATP production was inhibited by oligomycin, suggesting that metformin treatment significantly increases lactic acid levels in a glycolysis-dependent mechanism.…”

Maresin 1 resolves aged‐associated macrophage inflammation to improve bone regeneration

“…Chronic increase in the number of inflammatory cells and the amount of inflammatory cytokines has been linked to dysfunctional cellular differentiation and dysregulated matrix production at the site of tissue injury. 1,2 This phenomenon has been identified as a potential cause of the dysregulated tissue repair and decreased regeneration capacity after acute injury in advanced age. 3,4 Bone fracture healing is one regenerative process hindered by inflammaging.…”