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Comments on Kumar, Sandeep et al. (2013) International Worm Meeting "An ACE inhibitor extends Caenorhabditis elegans life span." (0)
Overview
Kumar, Sandeep, Dietrich, Nicholas, & Kornfeld, Kerry (2013). An ACE inhibitor extends Caenorhabditis elegans life span presented in International Worm Meeting. Unpublished information; cite only with author permission.
Aging is characterized by progressive, degenerative changes in many organ systems. Age-related degeneration of somatic tissues is a major contributor to disability and death. Treatments that delay age-related degeneration of humans are desirable, but no drugs that delay normal human aging are available. To identify drugs that delay age-related degeneration, we used the C. elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. We showed that captopril, an angiotensin converting enzyme (ACE) inhibitor used to treat high blood pressure, extended mean life span significantly. Captopril inhibits the enzyme ACE in humans, and the worm homolog of ACE is encoded by the acn-1 gene. We discovered that reducing the activity of acn-1 extended the mean life span of worms. acn-1 has previously been shown to play a role in larval molting. Combining treatment with captopril and reducing the activity of acn-1 did not have an additive effect on life span extension, indicating that these interventions may affect the same pathway. Captopril treatment and acn-1 RNAi can further extend the life span of many long-lived mutants, including mutants with defects in caloric intake, mitochondrial function, and insulin/IGF-1 signaling. However, captopril treatment and acn-1 RNAi did not extend the life span of daf-16 mutants. Based on these findings, we hypothesize that captopril extends life span by inhibition of the acn-1 gene, and this life span extension requires DAF-16, the target of the insulin/IGF-1 signaling pathway. The ACE pathway has been implicated in life span regulation in rodents, suggesting this may be an evolutionarily conserved system of life span regulation.
Affiliation:
- Development Biology, Washington University School of Medicine, St. Louis, MO.