Skeletal muscle mitochondrial dysfunction is associated with increased Gdf15 expression and circulating GDF15 levels...

Area of Science:

• Aging research
• Molecular biology
• Metabolic studies

Background:

• Growth differentiation factor-15 (GDF15) is a biomarker for various diseases.
• Circulating GDF15 levels increase with age, but the source in aging is unclear.
• Mitochondrial dysfunction and integrated stress response (ISR) can induce Gdf15 expression.

Purpose of the Study:

• To identify the organ source of elevated circulating GDF15 during aging.
• To investigate the association between metabolic/mitochondrial dysfunction and GDF15 levels in aging.
• To compare GDF15 expression and metabolic parameters in young versus middle-aged mice.

Main Methods:

• Metabolic phenotyping of young (12-week) and middle-aged (52-week) C57BL/6J mice.
• Measurement of circulating GDF15 levels.
• Analysis of tissue-specific Gdf15 expression patterns.

Main Results:

• Gdf15 expression was significantly increased in the skeletal muscle of middle-aged mice.
• No significant increase in Gdf15 expression was observed in liver, adipose tissue, kidney, or heart.
• Middle-aged mice exhibited impaired insulin sensitivity and mitochondrial respiratory capacity.

Conclusions:

• Skeletal muscle is a primary contributor to increased circulating GDF15 levels during aging.
• Early alterations in skeletal muscle mitochondrial function and metabolism are linked to elevated GDF15 in aging.
• These findings provide insights into the molecular mechanisms underlying aging-related biomarker changes.