FGF21 alleviates chronic inflammatory injury in the aging process through modulating polarization of macrophages

Area of Science:

• Cellular senescence
• Immunology
• Metabolic signaling

Background:

• Fibroblast Growth Factor 21 (FGF21) is known to extend lifespan and delay aging.
• The precise mechanisms by which FGF21 impacts hepatic senescence remain unclear.
• Understanding FGF21's role in liver aging is crucial for developing anti-aging interventions.

Purpose of the Study:

• To investigate the effects of FGF21 on hepatic senescence in aging mice.
• To elucidate the underlying molecular mechanisms, particularly involving macrophage polarization and signaling pathways.

Main Methods:

• Administration of FGF21 or metformin to 14-month-old male mice for 6 months.
• Analysis of senescence markers (SASP, P53, P16) and macrophage polarization (M1/M2) in liver tissues.
• In vitro studies using THP-1 macrophages and co-culture systems with hepatocytes to examine FGF21's effects on macrophage polarization and inflammatory responses via AMPK and NF-κB pathways.

Main Results:

• FGF21 treatment alleviated liver injury and reduced senescence markers in aging mice.
• FGF21 induced a shift from M1 to M2 macrophage polarization in the liver.
• FGF21's effects on macrophages were mediated by the AMPK pathway, which in turn influenced the NF-κB signaling pathway.
• FGF21-treated macrophages reduced pro-inflammatory factor-induced senescence in co-cultured hepatocytes.

Conclusions:

• FGF21 effectively alleviates hepatic senescence and liver injury in aging mice.
• The mechanism involves modulating macrophage polarization from M1 to M2 phenotypes.
• This FGF21-induced macrophage polarization is dependent on the AMPK/NF-κB signaling cascade.
• FGF21 represents a potential therapeutic target for mitigating age-related liver damage.