Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice
Karoline Degenhardt1,2,3, Jessica Wagner1,2,3, Angelos Skodras1,2
1German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany.
Abstract:
Medin is the most common amyloid known in humans, as it can be found in blood vessels of the upper body in virtually everybody over 50 years of age. However, it remains unknown whether deposition of Medin plays a causal role in age-related vascular dysfunction. We now report that aggregates of Medin also develop in the aorta and brain vasculature of wild-type mice in an age-dependent manner. Strikingly, genetic deficiency of the Medin precursor protein, MFG-E8, eliminates not only vascular aggregates but also prevents age-associated decline of cerebrovascular function in mice. Given the prevalence of Medin aggregates in the general population and its role in vascular dysfunction with aging, targeting Medin may become a novel approach to sustain healthy aging.
Insights
Medin amyloid aggregates are common in aging humans and mice. Targeting the Medin precursor protein MFG-E8 prevents age-related vascular dysfunction in mice, suggesting a new approach for healthy aging.
Area of Science:
- Cardiovascular Science
- Neuroscience
- Aging Research
Background:
- Medin is the most prevalent human amyloid, found in blood vessels of individuals over 50.
- The role of Medin deposition in age-related vascular dysfunction is currently unknown.
Purpose of the Study:
- To investigate the role of Medin in age-dependent vascular dysfunction.
- To determine if targeting Medin or its precursor impacts vascular aging.
Main Methods:
- Age-dependent development of Medin aggregates was studied in wild-type mice aortas and brain vasculature.
- The effect of genetic deficiency of MFG-E8 (Medin precursor) on vascular aggregates and cerebrovascular function was assessed.
Main Results:
- Medin aggregates were found to develop in mouse aorta and brain vasculature in an age-dependent manner.
- Genetic deficiency of MFG-E8 prevented Medin aggregate formation and age-associated decline in cerebrovascular function.
- This suggests MFG-E8 is crucial for Medin aggregation and subsequent vascular dysfunction.
Conclusions:
- Medin aggregation is linked to age-related vascular dysfunction.
- Targeting MFG-E8 may be a promising therapeutic strategy to maintain vascular health during aging.
- This research opens new avenues for interventions promoting healthy aging.
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