Activated GDF11/8 subforms predict cardiovascular events and mortality in humans.

Area of Science:

• Biochemistry
• Cardiovascular Medicine
• Gerontology

Background:

• Growth Differentiation Factors 11 and 8 (GDF11/8) exist in latent and active forms.
• The prognostic value of specific GDF11/8 forms in disease is not well understood.

Purpose of the Study:

• To investigate the predictive value of activated GDF11/8 levels for cardiovascular events, mortality, and dementia.
• To explore the role of GDF11/8 activation in aging-related diseases.

Main Methods:

• Development of a dual-specific aptamer to detect activated GDF11/8.
• Analysis of GDF11/8 levels in large patient cohorts (11,609 and 4,110 individuals).
• Association of aptamer-detected GDF11/8 levels with cardiovascular events, all-cause mortality, and dementia risk.

Main Results:

• Low activated GDF11/8 levels strongly predicted cardiovascular events (HR=0.43) and all-cause mortality (HR=0.33) in a large cohort.
• Low activated GDF11/8 levels also predicted increased 8-year dementia risk (HR=0.66) in a separate cohort.
• Findings were replicated using a GDF8-selective aptamer, though with a smaller effect size.

Conclusions:

• Activated GDF11/8 is a significant predictor of adverse cardiovascular and mortality outcomes.
• Activated GDF11/8 may play a role in age-related cognitive decline, specifically dementia.
• GDF11/8 activation is a potential biomarker and therapeutic target for aging-related diseases.