Circadian clock genes’ overexpression in Drosophila alters diet impact on lifespan

Abstract

Diet restriction is one of the most accurately confirmed interventions which extend lifespan. Genes coding circadian core clock elements are known to be the key controllers of cell metabolism especially in aging aspect. The molecular mechanisms standing behind the phenomenon of diet-restriction-mediated life extension are connected to circadian clock either. Here we investigate the effects of protein-rich and low-protein diets on lifespan observed in fruit flies overexpressing core clock genes (cry, per, Clk, cyc and tim). The majority of core clock genes being upregulated in peripheral tissues (muscles and fat body) on protein-rich diet significantly decrease the lifespan of male fruit flies from 5 to 61%. Nevertheless, positive increments of median lifespan were observed in both sexes, males overexpressing cry in fat body lived 20% longer on poor diet. Overexpression of per also on poor medium resulted in life extension in female fruit flies. Diet restriction reduces mortality caused by overexpression of core clock genes. Cox-regression model revealed that diet restriction seriously decreases mortality risks of flies which overexpress core clock genes. The hazard ratios are lower for flies overexpressing clock genes in fat body relatively to muscle-specific overexpression. The present work suggests a phenomenological view of how two peripheral circadian oscillators modify effects of rich and poor diets on lifespan and hazard ratios.

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Acknowledgements

We are grateful to Dr. Patrick Emery (University of Massachusetts Medical School, USA), Dr. Paul Hardin (Texas A&M University, USA), Dr. Keshishian (Yale University, USA), Dr. Laurent Seroude (Queen’s University, Canada) and the Bloomington stock center (Indiana University, USA) for providing the Drosophila strains.

Funding

The study was carried out within the framework of the state task on themes “Molecular-genetic mechanisms of aging, lifespan, and stress resistance of Drosophila melanogaster”, state registration No. AAAA-A18-118011120004-5 and “A combination of factors of different nature (low temperature, lack of lighting, restrictive diet, and geroprotector) to maximize the lifespan of Drosophila. Complex UrB RAS Programme” No. 18-7-4-23, state registration No. AAAA-A18-118011120008-3.

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Correspondence to Alexey Moskalev.

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Solovev, I., Shegoleva, E., Fedintsev, A. et al. Circadian clock genes’ overexpression in Drosophila alters diet impact on lifespan. Biogerontology 20, 159–170 (2019). https://doi.org/10.1007/s10522-018-9784-2

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Keywords

  • Circadian clock
  • Aging
  • Lifespan
  • Diet restriction
  • Feeding assay
  • Drosophila melanogaster