Chronic inflammation induces telomere dysfunction and accelerates ageing in mice.

Area of Science:

• Aging and Gerontology
• Molecular Biology
• Inflammation Research

Background:

• Chronic inflammation is linked to normal and pathological aging processes.
• The transcription factor NF-κB plays a role in inflammatory responses.

Purpose of the Study:

• To investigate the role of the NF-κB pathway in aging.
• To determine if chronic inflammation can induce premature aging.

Main Methods:

• Mice lacking the nfkb1 subunit of NF-κB (nfkb1(-/-)) were studied.
• Cell senescence, DNA damage, and tissue regeneration were assessed.
• The effects of anti-inflammatory and antioxidant treatments were evaluated.

Main Results:

• nfkb1(-/-) mice exhibited chronic, low-grade inflammation and premature aging.
• These mice showed reduced liver and gut regeneration.
• nfkb1(-/-) fibroblasts displayed aggravated cell senescence via NF-κB, COX-2, and ROS feedback.
• Senescent cell accumulation was linked to telomere dysfunction and DNA damage.
• Anti-inflammatory/antioxidant treatments blocked senescent cell accumulation and rescued regeneration.
• Senescent cell frequency predicted lifespan in mice.

Conclusions:

• Systemic chronic inflammation accelerates aging by exacerbating telomere dysfunction and cell senescence.
• NF-κB inhibition leads to premature aging phenotypes through ROS-mediated mechanisms.
• Targeting inflammation and oxidative stress may offer therapeutic strategies for age-related decline.