Gut microbiota lipopolysaccharide accelerates inflamm-aging in mice

Area of Science:

• Immunology
• Microbiology
• Gerontology

Background:

• Aging is characterized by chronic inflammation, known as inflamm-aging.
• This process involves immune system dysregulation and alterations in gut microbiota composition.
• The relationship between aging and lipopolysaccharide (LPS)-induced inflammation from gut microbes was investigated.

Purpose of the Study:

• To explore the impact of aging on gut microbiota and its associated inflammatory responses.
• To determine the role of lipopolysaccharide (LPS) in age-related inflammation.
• To identify potential molecular markers of inflamm-aging.

Main Methods:

• Comparative analysis of gut microbiota composition in young and aged mice.
• Quantification of plasmatic and fecal LPS levels.
• Assessment of inflammatory markers (p16, NF-κB) and protein expression (SAMHD1, CDK-2, Cyclin E) in colonic tissues.
• In vitro experiments using peritoneal macrophages treated with fecal LPS fractions.

Main Results:

• Aging altered gut microbiota, increasing the Firmicutes/Bacteroidetes ratio and elevating LPS levels.
• Aged mice exhibited increased p16 and SAMHD1 expression and NF-κB activation in the colon.
• Fecal LPS from aged mice enhanced inflammatory responses in macrophages via TLR4, upregulating p16, SAMHD1, and NF-κB.

Conclusions:

• Gut microbiota LPS contributes to inflamm-aging by promoting NF-κB activation.
• Increased p16 and SAMHD1 expression are associated with aging and LPS-induced inflammation.
• SAMHD1 may serve as a potential biomarker for inflamm-aging.