Comparative approaches to facilitate the discovery of prolongevity interventions: Effects of tocopherols on lifespan of three invertebrate species

Abstract

SummaryMany compounds hold promise for pharmacologic manipulation of aging. However, such claims are difficult to investigate due to time and budget constraints. Here, we took a comparative approach, using short-lived invertebrate species, to directly test the effects of two tocopherols (vitamin E) on longevity. γ-tocopherol represents the most abundant tocopherol in the Western diet, while α-tocopherol is selectively enriched in human plasma. Both isoforms demonstrate antioxidant activity and are proposed to have anti-aging activities. We compared the effects of α-and γ-tocopherol supplementation on lifespan in three invertebrate species. γ-, but not α-, tocopherol slightly extended lifespan in nematodes, but neither significantly affected lifespan in two fly species. This study shows that a comparative approach, utilizing multiple invertebrate species, can increase the robustness of invertebrate-based pilot screens for prolongevity interventions.Pharmacological and nutritional approaches to retard aging and increase longevity have been proposed (Floyd, 2006, Joseph et al., 2005. Large-scale screens are being considered for a number of model organisms to accelerate discovery of compounds with the greatest potential for extending lifespan (Bauer et al., 2004, Wang et al., 2004. One class of compounds with potentially beneficial effects on aging are the tocopherol isomers found in Vitamin E and which are found naturally in plant oils (Ames et al., 2005). Vitamin E is a mixture of several related tocopherol and tocotrienol isomers, including the α-and γ-tocopherols. The Western diet is enriched in γ-tocopherol, but α-tocopherol is selectively retained in human plasma (Jiang et al., 2001, Tucker andTownsend, 2005). Both tocopherols are derived from fatty acids and exist within membranes, where they affect membrane fluidity and can act as antioxidants.The high antioxidant capacity of vitamin E makes it a candidate for a prolongevity therapy, since aging is correlated with increased oxidative stress in cells (Ames et al., 1993, Harman, 1 These authors contributed equally to this work. * Corresponding author: CAW: Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore MD 21224; Tel: 410-558-8566; Fax: 410-558-8323; wolkowca@grc.nia.nih.gov.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. One efficient strategy for directly examining whether these compounds have any effect on lifespan is to determine whether supplementation can affect lifespan in short-lived invertebrate species, which offer models for aging in...

The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster

“…1a-d). The base and DR diets used here are routinely employed in aging intervention and DR studies in D. melanogaster (Bross et al 2005;Bass et al 2007a;Zou et al 2007). Our findings suggest that supplementation of resveratrol at up to 200 μM is not sufficient to promote longevity of flies under standard or restricted dietary conditions.…”

Lifelongα-Tocopherol Supplementation Increases the Median Life Span of C57BL/6 Mice in the Cold but Has Only Minor Effects on Oxidative Damage

“…Firstly, vitamin E supplementation may indeed quench ROS and reduce oxidative stress, but this may have no or little impact on aging and life span if the importance of these processes has been overestimated in vivo. 17 Secondly, Vitamin E may scavenge ROS, and ROS may be important in the aging process, but this effect might be offset by a parallel compensating impacts on the endogenous antioxidant system, or indeed on any system involved in redox status or oxidative damage, similar to those reported following vitamin C supplementation. 25,26 Thirdly, because body mass and energy metabolism affect both free-radical production and life span, 7,27,28 if vitamin E supplementation influences one or both of these factors, this could offset any potential benefits.…”

“…11 The effects on life span following vitamin E supplementation in animal models are similarly confused. Using a comparative approach, Zou et al 17 reported that ␥-tocopherol, but not ␣-tocopherol, extended life span in Caenorhabditis elegans, but that neither isoform had any life span effect in Drosophila melanogastor or Anastrepha ludens. An increase in median/mean life span has been reported in various strains of mice following vitamin E supplementation [18][19][20][21] or following supplementation with a mixed antioxidant diet containing vitamins E and C. 22 However, other studies report no effect on life span or on oxidative stress following vitamin E supplementation or when using a mixed antioxidant diet.…”

Effect of semolina-jaggery diet on survival and development ofDrosophila melanogaster

“…1 Flies exhibit a short generation time and high fecundity and have a well-differentiated central nervous system, cardiac anatomy, malphigian tubules (mammalian kidney analogs), and fat body (mammalian adipose tissue analogs). [2][3][4][5][6][7] Also, the ease of inducing gene knockouts and mutagenesis has rendered D. melanogaster as a powerful model to pursue demographic studies on various metabolic disorders. 8 Although rearing flies is a relatively simple process, it requires knowledge of the appropriate individual components in media formulation.…”