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Flies selected for longevity retain a young gene expression profile

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Abstract

We investigated correlated responses in the transcriptomes of longevity-selected lines of Drosophila melanogaster to identify pathways that affect life span in metazoan systems. We evaluated the gene expression profile in young, middle-aged, and old male flies, finding that 530 genes were differentially expressed between selected and control flies when measured at the same chronological age. The longevity-selected flies consistently showed expression profiles more similar to control flies one age class younger than control flies of the same age. This finding is in accordance with a younger gene expression profile in longevity-selected lines. Among the genes down-regulated in longevity-selected lines, we found a clear over-representation of genes involved in immune functions, supporting the hypothesis of a life-shortening effect of an overactive immune system, known as inflammaging. We judged the physiological age as the level of cumulative mortality. Eighty-four genes were differentially expressed between the control and longevity-selected lines at the same physiological age, and the overlap between the same chronological and physiological age gene lists included 40 candidate genes for increased longevity. Among these candidates were genes with roles in starvation resistance, immune response regulation, and several that have not yet been linked to longevity. Investigating these genes would provide new knowledge of the pathways that affect life span in invertebrates and, potentially, mammals.

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Acknowledgments

The authors are grateful to Doth Andersen and Marie Rosenstand Hansen for technical assistance, to Mogens Kruhøffer, AROS Applied Biotechnologies, for RNA extraction and hybridization, to Suresh Rattan, Jesper G Sørensen, Torsten N Kristensen, Corneel Vermeulen, and Janneke Wit and anonymous reviewers for helpful comments on the manuscript, and to the Danish Natural Sciences Research Council (frame and center grants to VL), Villum Kann Rasmussen Foundation (VL), Lundbeck Foundation and Carlsbergfondet (stipend to PSa), and the European Commission, within the 6th Framework Program (grant to PSø, contract no. FOOD-CT-2006-016250).

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Authors and Affiliations

  1. Aarhus Centre for Environmental Stress Research (ACES), Department of Biological Sciences, Aarhus University, Ny Munkegade 114, 8000, Aarhus C, Denmark

    Pernille Sarup & Volker Loeschcke

  2. Department of Genetics and Biotechnology, Danish Institute of Agricultural Sciences, Aarhus University, Blichers Allé 20, 8830, Tjele, Denmark

    Peter Sørensen

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  1. Pernille Sarup
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Correspondence to Pernille Sarup.

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Sarup, P., Sørensen, P. & Loeschcke, V. Flies selected for longevity retain a young gene expression profile. AGE 33, 69–80 (2011). https://doi.org/10.1007/s11357-010-9162-8

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  • DOI: https://doi.org/10.1007/s11357-010-9162-8

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