Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

Citations Over TimeTop 1% of 2014 papers

Abstract

Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-κB induces premature ageing in mice. We also show that these mice have reduced regeneration in liver and gut. nfkb1(-/-) fibroblasts exhibit aggravated cell senescence because of an enhanced autocrine and paracrine feedback through NF-κB, COX-2 and ROS, which stabilizes DNA damage. Preferential accumulation of telomere-dysfunctional senescent cells in nfkb1(-/-) tissues is blocked by anti-inflammatory or antioxidant treatment of mice, and this rescues tissue regenerative potential. Frequencies of senescent cells in liver and intestinal crypts quantitatively predict mean and maximum lifespan in both short- and long-lived mice cohorts. These data indicate that systemic chronic inflammation can accelerate ageing via ROS-mediated exacerbation of telomere dysfunction and cell senescence in the absence of any other genetic or environmental factor.

Related Papers

• → Inhibition of both paracrine and autocrine VEGF/ VEGFR-2 signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias(2001)269 cited
• → Computational model and microfluidic platform for the investigation of paracrine and autocrine signaling in mouse embryonic stem cells(2009)40 cited
• → Renal Autocrine and Paracrine Signaling: A Story of Self-protection(2020)27 cited
• → Autocrine/Paracrine Function of Parathyroid Hormone-Related Peptide in Rat Osteoblast-like Cells(1993)16 cited
• The possible role of IL—1 autocrine and paracrine in mesangial cell(MSc)(1992)