Age-Specific Variation in Immune Response in Drosophila Melanogaster Has a Genetic Basis

By Felix, Tashauna M.; Hughes, Kimberly A. et al. | Genetics, July 2012 | Go to article overview

Age-Specific Variation in Immune Response in Drosophila Melanogaster Has a Genetic Basis


Felix, Tashauna M., Hughes, Kimberly A., Stone, Eric A., Drnevich, Jenny M., Leips, Jeff, Genetics


ABSTRACT Immunosenescence, the age-related decline in immune system function, is a general hallmark of aging. While much is known about the cellular and physiological changes that accompany immunosenescence, we know little about the genetic influences on this phenomenon. In this study we combined age-specific measurements of bacterial clearance ability following infection with whole-genome measurements of the transcriptional response to infection and wounding to identify genes that contribute to the natural variation in immunosenescence, using Drosophila melanogaster as a model system. Twenty inbred lines derived from nature were measured for their ability to clear an Escherichia coli infection at 1 and 4 weeks of age. We used microarrays to simultaneously determine genome-wide expression profiles in infected and wounded flies at each age for 12 of these lines. Lines exhibited significant genetically based variation in bacterial clearance at both ages; however, the genetic basis of this variation changed dramatically with age. Variation in gene expression was significantly correlated with bacterial clearance ability only in the older age group. At 4 weeks of age variation in the expression of 247 genes following infection was associated with genetic variation in bacterial clearance. Functional annotation analyses implicate genes involved in energy metabolism including those in the insulin signaling/TOR pathway as having significant associations with bacterial clearance in older individuals. Given the evolutionary conservation of the genes involved in energy metabolism, our results could have important implications for understanding immunosenescence in other organisms, including humans.

UNDERSTANDING the genetic architecture of senescence, the physiological decline that occurs with increasing age, is a long-standing problem in biology. Most studies in this area have focused on elucidating the genetic basis of heritable variation in age-specific mortality and longevity (Dudycha and Tessier 1999; Guarente and Kenyon 2000; Wilson et al. 2007, 2008; Blomquist 2010; Fontana et al. 2010) and several candidate genes contributing to this variation have been identified (De Luca et al. 2003; Burger and Promislow 2006; Paaby and Schmidt 2008; Jazwinski et al. 2010; Soerensen et al. 2010). In contrast, we know little about the genes that influence age-related functional declines in life history or physiological traits that may in turn affect age-specific mortality and limit life span (Burger and Promislow 2006; Charmantier et al. 2006; Leips et al. 2006; Lesser et al. 2006; Nussey et al. 2008a). Functional decline in such traits with age can reduce fitness in natural environments (Dudycha and Tessier 1999; Wilson et al. 2007; Bowler and Terblanche 2008; Nussey et al. 2008b; Wilson et al. 2008; Blomquist 2010; Ceballos and Kiørboe 2011) and for humans influences the quality of life in older individuals. As such, knowledge of the genes that influence age-related deterioration in functional traits is important for understanding the genetic basis of evolutionary fitness as well as general aspects of health in the aging organism. In addition, this information would provide insight into the genetic interrelationships between these traits and longevity and increase our understanding of correlated evolutionary responses among them (Burger and Promislow 2006).

Immunosenescence, the age-related decline in immune function, is a general consequence of aging (Kaaya and Darji 1988; Kogut et al. 2002; Laws et al. 2004; Hillyer et al. 2005; Zerofsky et al. 2005; Pawelec 2006; Kovacs et al. 2009; Leips 2009; Scholz et al. 2009). Early studies of immunosenescence primarily focused on deterioration of the adaptive immune response with age, that component of the immune response that provides immunological memory and is uniquely found in vertebrates. However, an increasing number of studies indicate that the innate immune response, the nonspecific response to infection, also shows signs of deterioration with age (Butcher et al. …

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Age-Specific Variation in Immune Response in Drosophila Melanogaster Has a Genetic Basis
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