Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster.
The discovery of life extension in Caenorhabditis elegans treated with anticonvulsant medications has raised the question whether these drugs are prospective anti-aging candidate compounds. The impact of these compounds on neural modulation suggests that they might influence the chronic diseases of aging as well. Lamotrigine is a commonly used anticonvulsant with a relatively good adverse-effects profile. In this study, we evaluated the interaction between the impacts of lamotrigine on mortality rate, lifespan, metabolic rate and locomotion. It has been proposed in a wide range of animal models that there is an inverse relationship between longevity, metabolic rate, and locomotion. We hypothesized that the survival benefits displayed by this compound would be associated with deleterious effects on health span, such as depression of locomotion. Using Drosophila as our model system, we found that lamotrigine decreased mortality and increased lifespan in parallel with a reduction in locomotor activity and a trend towards metabolic rate depression. Our findings underscore the view that assessing health span is critical in the pursuit of useful anti-aging compounds.
Department of Pharmaceutical Sciences, University of California-Irvine, Irvine, CA 92697, USA.
Agnesa
A
Avanesian
Behnood
B
Khodayari
Jeffery S
JS
Felgner
Mahtab
M
Jafari
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000187:drug effects / Q000502:physiology*; D000077213:Lamotrigine; D008017:Life Expectancy; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014227:Triazines; D000077213:Lamotrigine