title: Combined statin and angiotensin-converting enzyme (ACE) inhibitor treatment increases the lifespan of long-lived F1 male mice.
abstract: Statins, such as simvastatin, and ACE inhibitors (ACEis), such as ramipril, are standard therapies for the prevention and treatment of cardiovascular diseases. These types of drugs are commonly administered together. More recently, angiotensin II type 1 receptor (AT1R) antagonists, such as candesartan cilexetil (candesartan), have been used in the place of, or in combination with, ACEis. Here, we investigated the effects of simvastatin and ramipril single and combination therapy, and candesartan treatment on the lifespan of isocalorically fed, long-lived, B6C3F1 mice. Males were used for their relative endocrine simplicity and to minimize animal usage. The drugs were administered daily in food. The simvastatin and ramipril combination therapy significantly increased the mean and median lifespan by 9 %. In contrast, simvastatin, ramipril, or candesartan monotherapy was ineffective. All groups consumed the same number of calories. Simvastatin, alone or administered with ramipril, decreased body weight without changing caloric consumption, suggesting it may alter energy utilization in mice. Combination therapy elevated serum triglyceride and glucose levels, consistent with altered energy homeostasis. Few significant or consistent differences were found in mortality-associated pathologies among the groups. Simvastatin treatment did not reduce normal serum cholesterol or lipid levels in these mice, suggesting that the longevity effects may stem from the pleiotropic, non-cholesterol-related, effects of statins. Together, the results suggest that statins and ACEis together may enhance mouse longevity. Statins and ACE inhibitors are generally well-tolerated, and in combination, they have been shown to increase the lifespan of normotensive, normocholesterolemic humans.
authors: Department of Biochemistry, University of California at Riverside, Riverside, CA, 92521, USA. spindler@ucr.edu.
authors: Stephen R
authors: SR
authors: Spindler
authors: Department of Biochemistry, University of California at Riverside, Riverside, CA, 92521, USA.
authors: Patricia L
authors: PL
authors: Mote
authors: Department of Statistics, University of California at Riverside, Riverside, CA, 92521, USA.
authors: James M
authors: JM
authors: Flegal
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D002853:Chromatography, Liquid; D015331:Cohort Studies; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017257:Ramipril / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013777:Tetrazoles; D014280:Triglycerides; D002784:Cholesterol; D019821:Simvastatin; D017257:Ramipril; C081643:candesartan
keywords: ACE inhibitors; Angiotensin II receptor antagonists; Life span; Longevity; Statins