Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span

Animal aging is characterized by progressive,degenerative changes in many organ systems. because age-related degeneration is a major contributor to disability and death in humans,treatments that delay age-related degeneration are desirable. however,no drugs that delay normal human aging are currently available. to identify drugs that delay age-related degeneration,we used the powerful caenorhabdtitis elegans model system to screen for fda-approved drugs that can extend the adult lifespan of worms. here we show that captopril extended mean lifespan. captopril is an angiotensin-converting enzyme (ace) inhibitor used to treat high blood pressure in humans. to explore the mechanism of captopril,we analyzed the acn-1 gene that encodes the c. elegans homolog of ace. reducing the activity of acn-1 extended the mean life span. furthermore,reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance,indicating that acn-1 influences aging. captopril could not further extend the lifespan of animals with reduced acn-1,suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. to define the relationship with previously characterized longevity pathways,we analyzed mutant animals. the lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency,and did not require sir-2.1,hsf-1 or rict-1,suggesting that acn-1 functions by a distinct mechanism. the interactions with the insulin/igf-1 pathway were complex,since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds,consistent with the model that they act by the same mechanism. these results identify a new drug and a new gene that can extend the lifespan of worms and suggest new therapeutic strategies for addressing age-related degenerative changes. © 2016 kumar et al.