Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster

Mariann M. Gabrawy, Sarah Campbell, Mary Anna Carbone, Tatiana V. Morozova, Gunjan H. Arya, Lavanya B. Turlapati, Jeremy D. Walston, Michelle Starz-Gaiano, Logan Everett, Trudy F.C. Mackay, Jeff Leips, Peter M. Abadir

Research output: Contribution to journalArticle

Abstract

Physical resiliency declines with age and comorbid conditions. In humans, angiotensin-converting enzyme (ACE) has been associated with attenuation of the decline in physical performance with age. ACE-inhibitor compounds, commonly prescribed for hypertension, often have beneficial effects on physical performance however the generality of these effects are unclear. Here, we tested the effects of the ACE-inhibitor Lisinopril on life span, and age-specific speed, endurance, and strength using three genotypes of the Drosophila melanogaster Genetic Reference Panel. We show that age-related decline in physical performance and survivorship varies with genetic background. Lisinopril treatment increased mean life span in all Drosophila Genetic Reference Panel lines, but its effects on life span, speed, endurance, and strength depended on genotype. We show that genotypes with increased physical performance on Lisinopril treatment experienced reduced age-related protein aggregation in muscle. Knockdown of skeletal muscle-specific Ance, the Drosophila ortholog of ACE, abolished the effects of Lisinopril on life span, implying a role for skeletal muscle Ance in survivorship. Using transcriptome profiling, we identified genes involved in stress response that showed expression changes associated with genotype and age-dependent responsiveness to Lisinopril. Our results demonstrate that Ance is involved in physical decline and demonstrate genetic variation in phenotypic responses to an ACE inhibitor.

Original languageEnglish (US)
Pages (from-to)1844-1852
Number of pages9
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume74
Issue number12
DOIs
StatePublished - Nov 13 2019

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Keywords

  • Aging
  • Angiotensin
  • Genetic variation
  • Locomotion
  • Muscle

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Gabrawy, M. M., Campbell, S., Carbone, M. A., Morozova, T. V., Arya, G. H., Turlapati, L. B., Walston, J. D., Starz-Gaiano, M., Everett, L., Mackay, T. F. C., Leips, J., & Abadir, P. M. (2019). Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster. The journals of gerontology. Series A, Biological sciences and medical sciences, 74(12), 1844-1852. https://doi.org/10.1093/gerona/glz152