Dietary restriction in Drosophila
Introduction
Extension of lifespan by dietary restriction (DR) was first discovered in rodents (McCay et al., 1935), and the phenomenon has been most intensively studied in mice and rats (Chung et al., 2002, Kim et al., 2002, Masoro, 1998, Masoro, 2000, Masoro, 2002, Merry, 2002, Weindruch and Walford, 1988, Yu and Chung, 2001). Reduction of nutrient intake also extends lifespan in diverse invertebrate species and has become the subject of detailed study in model organisms, including the yeast Saccharomyces cerevisiae (Anderson et al., 2003, Jiang et al., 2000, Jiang et al., 2002, Kaeberlein et al., 2004, Lin et al., 2000, Lin et al., 2004, Sinclair, 2005, Guarente, 2005), the nematode worm Caenorhabditis elegans (Houthoofd et al., 2003, Johnson et al., 1990, Klass, 1977, Lakowski and Hekimi, 1998; Walker et al., 2005) and the fruit fly Drosophila melanogaster (Chapman and Partridge, 1996, Chippindale et al., 1993, Partridge et al., 1987). The molecular mechanisms by which DR extends lifespan have not been fully revealed in any organism and it therefore remains unproven that extension of lifespan by DR is accomplished by similar mechanisms in different species. However, the almost universal extension of lifespan by reduced nutrient intake is suggestive of evolutionary conservation. Information on the mechanisms by which DR extends lifespan in these invertebrates is therefore likely to inform our understanding of the process in mammals.
The fruit fly D. melanogaster has many strengths as a model organism for the study of extension of lifespan by DR. Unlike either yeast or C. elegans, but similar to humans, Drosophila is an obligate aerobe, which may have a bearing on the types of ageing-related damage that are accumulated. Drosophila is also an excellent organism for studies of demography, which have been particularly informative about the mechanisms by which DR reduces mortality rate (Mair et al., 2003). The fly has all the usual advantages of a model organism for genetic manipulation and molecular and physiological analysis. It is also dioecious (has separate females and males) and can therefore be used to investigate sex differences in response to DR.
Two important questions about DR in any organism are: (1) What are the mechanisms by which nutrients are sensed and the response to DR initiated and controlled? (2) What forms of adverse physiology, damage or pathology are ameliorated by DR to reduce death rate? In this review, we consider what is known about the response to DR in Drosophila, focusing particularly on these issues. Several studies have examined the effects of pre-adult nutrition on adult lifespan in Drosophila, and found no extension of lifespan with reduction of food supply (e.g. Tu and Tatar, 2003, Zwaan et al., 1991). We therefore confine our attention to the effects of DR that is applied solely during the adult period.
Section snippets
Dietary restriction in Drosophila
Laboratory cultures of Drosophila are maintained on a food medium that consists of nutritional components dissolved or suspended in an agar gel. The precise composition of the food medium varies considerably between different laboratories and medium types, but the usual ingredients include sugar, killed yeast and corn flour or corn meal. In addition, the surface of the food medium can be seeded with live yeast that grows on the nutrient gel and is used as a food supply by Drosophila. DR in
Mechanisms initiating and controlling the response to DR in Drosophila
A basic dichotomy in the way that lifespan might be extended by DR is either through tissue-specific nutrient-sensing followed by neural or endocrine signalling to other sites, or through direct sensing of nutrients by cells throughout the body. In C. elegans, ablation of chemosensory neurons extends lifespan, which could indicate that neural sensing of nutrients is important in the extension of lifespan by DR (Alcedo and Kenyon, 2004, Apfeld and Kenyon, 1999). Work on the role of
The mechanisms by which DR reduces death rate in Drosophila
A notable feature of the response to DR in rodents is that the appearance of multiple forms of ageing-related damage, pathology and disease is delayed, and the animals are maintained in a youthful state for longer (Berrigan et al., 2002, Iwasaki et al., 1988a, Iwasaki et al., 1988b, Masoro, 2002, Weindruch and Walford, 1988). These features make the mechanisms by which DR extends lifespan of compelling interest. However, a major problem in identifying the mechanisms by which DR reduces death
Summary and future directions
Considerable progress has been made in developing robust protocols for extension of lifespan by DR in Drosophila. However, some basic features of the responses of lifespan and fecundity require further definition. Calories per se may not be the critical determinant of the increase in lifespan, and this issue requires exploration. Work with defined diets would help to resolve this and to standardise protocols in different laboratories.
At least two signalling systems, the IIS and TOR pathways,
Acknowledgements
We thank Scott Pletcher for his comments on the MS, two anonymous reviewers for helpful comments, the BBSRC and the Wellcome Trust for financial support and the Rank Prize Fund for providing the impetus for this review.
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2021, Insect Biochemistry and Molecular BiologyCitation Excerpt :Indeed, after 24 h of starvation, the levels of DILP2 and DILP5 in the hemolymph were reduced concomitant to their accumulation in the IPCs (Sudhakar et al., 2020). Dietary and caloric restriction are the nutritional regimes, which can be applied to adult Drosophila by restriction of live yeast in the medium or by the dilution of the whole food medium respectively (Partridge et al., 2005). Reduction of nutrient intake was shown to extend lifespan in a number of model organisms, including Drosophila (Chapman and Partridge, 1996; Lushchak et al., 2019).