Association between elevated expression of GDF15/GFRAL and sarcopenia risk.

Area of Science:

• Biomedical research
• Gerontology
• Molecular biology

Background:

• Glial cell line-derived neurotrophic factor family receptor α-like (GFRAL) is the sole receptor for growth differentiation factor 15 (GDF15).
• The specific role of the GDF15-GFRAL axis in sarcopenia pathogenesis is not well-defined.
• Sarcopenia, age-related muscle loss, poses a significant public health challenge.

Purpose of the Study:

• To investigate the association between serum levels of GDF15 and GFRAL and the risk of sarcopenia.
• To explore potential sex-specific effects of the GDF15-GFRAL axis on sarcopenia.
• To examine the role of the GDF15-GFRAL axis in skeletal muscle damage using preclinical models.

Main Methods:

• Analysis of serum GDF15 and GFRAL levels in White British and Chinese participants.
• Assessment of physical performance metrics.
• Single-cell RNA sequencing and immunohistochemical analyses in animal models.

Main Results:

• Elevated serum GDF15 and GFRAL levels correlate with an increased risk of sarcopenia.
• This association is more pronounced in individuals with low physical performance.
• GFRAL's detrimental impact on sarcopenia appears greater in women compared to men.
• Preclinical studies support the GDF15-GFRAL axis's role in skeletal muscle damage.

Conclusions:

• The GDF15-GFRAL axis is clinically relevant to sarcopenia risk and prevention.
• Further mechanistic studies are warranted to fully understand the axis's role in sarcopenia.
• Targeting the GDF15-GFRAL pathway may offer novel therapeutic strategies for sarcopenia.