Groupe Flatt
Evolution & Mechanisms of Aging and Life History

“…integrating an understanding of mechanisms into life history theory will be one of the most exciting tasks facing evolutionary biologists in the 21st century.”

Barnes & Partridge (2003), in Animal Behaviour

We study the genetic and physiological mechanisms underlying the evolution of life history traits, with a particular emphasis on aging.

- Which genes and polymorphisms underlie the evolution of aging and life history?

- What mechanisms underlie life history trade-offs, e.g. between reproduction and longevity?

- What are the mechanisms underlying life history plasticity?

One central focus of our research is on understanding how hormonal signaling pathways (e.g., insulin, juvenile hormone, and ecdysone) affect aging and trade-offs between reproduction and lifespan, immunity, and somatic maintenance.

Another focus is on understanding the genetic basis of evolutionary changes in lifespan and other life history traits in natural and laboratory populations.

To address these problems we combine the tools of evolutionary and functional genetics, genomics, physiology and experimental evolution in the fruit fly (Drosophila melanogaster).

Currently we are interested in two major problems:

One of our main interests is in understanding the evolutionary and functional genetics of aging and related life history traits in natural populations of Drosophila melanogaster. While molecular geneticists typically focus on major effects of induced mutations or transgenes, evolutionary geneticists work on much more subtle phenotypic differences caused by standing natural genetic variation, the substrate on which evolutionary change by natural selection is based upon. Although it is becoming increasingly clear that both molecular and evolutionary geneticists have been studying qualitatively different forms of genetic variation at the same loci, it is still unclear whether this also holds for genes affecting life span. For example, not all candidate loci with major effects on longevity may exhibit segregating allelic variation in natural populations. Thus, while the major lifespan effects identified by molecular gerontology may be of biomedical interest, they may be of only limited relevance for our understanding of the evolution of aging in natural populations. On the other hand, the rapid progress made by molecular biologists in identifying candidate mechanisms affecting aging enables evolutionary biologists to determine whether there is standing genetic variation for longevity genes in natural populations and whether they are under selection. We are interested in functionally characterizing natural allelic variation in genes known to affect Drosophila life span. To this end, we are working on the genomic characterization of (1) latitudinal life history differentiation and (2) lines artificially selected for increased lifespan. In a related project, we are also studying altitudinal life history differentiation.

Further reading:
Fabian, D, Kapun, M., Nolte, V., Kofler, R., Schmidt, P.S., Schlötterer, C., Flatt, T. 2012. Genome-wide patterns of latitudinal differentiation among populations of Drosophila melanogaster from North America. Molecular Ecology 21:4748–4769.

Orozco-terWengel, P., Kapun, M., Nolte, V., Kofler, R., Flatt, T., Schlötterer, C. 2012. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles. Molecular Ecology 21:4931-4941 [Cover Article, with Cover Image] [Commentary by M. K. Burke and A. D. Long. 2012. What paths do advantageous alleles take during short-term evolutionary change? Molecular Ecology 21:4913-4916].

Flatt, T., and P.S. Schmidt. 2009. Integrating evolutionary and molecular genetics of aging. Biochimica et Biophysica Acta 1790:951-962.

Flatt, T., and T.J. Kawecki. 2004. Pleiotropic effects of Methoprene-tolerant (Met), a gene involved in juvenile hormone metabolism, on life history traits in Drosophila melanogaster. Genetica 122:141-160.

Flatt, T. 2004. Assessing natural variation in genes affecting Drosophila lifespan.
Mechanisms of Ageing and Development 125:155-159.

Trade-offs between reproduction and lifespan are ubiquitous, but little is known about their underlying mechanisms. Recent work suggests that reproduction and life span might be linked by molecular signals produced by reproductive tissues. In the nematode C. elegans life span is extended if worms lack proliferating germ cells in the presence of an intact somatic gonad. This suggests that the gonad is the source of signals which physiologically modulate organismal aging. Our recent work has shown that such gonadal signals are also present in the fruit fly D. melanogaster, suggesting that the regulation of lifespan by the reproductive system is evolutionarily conserved. Ablation of germline stem cells in the fly extends lifespan and modulates components of insulin/insulin-like growth factor signaling (IIS) in peripheral tissues, a conserved pathway important in regulating growth, metabolism, reproduction, and aging. Thus, as of yet unidentified endocrine signals from the germline might converge onto IIS to regulate aging. Using a combination of experimental evolution, hormonal manipulation, and genetics we have also found that juvenile hormone (JH), a hormone downstream of IIS, mediates the physiological but not necessarily the evolutionary trade-off between lifespan and reproduction in Drosophila. Our current work focuses on understanding the details of how hormonal signaling mediates the trade-off between reproduction and life span. In particular, we are interested in studying the role of insulin signaling, the steroid hormone ecdysone, and lipid metabolism in this regulation.

Further reading:
Hansen, M.,* Flatt, T.*, and H. Aguilaniu*. 2013. Reproduction, Fat Metabolism, and Life Span: What Is the Connection? Cell Metabolism 17:10-19. [*Equal contribution].

Flatt, T. 2011. Survival costs of reproduction in Drosophila. Experimental Gerontology 46:369-375.

Flatt, T., and A. Heyland (Editors). 2011. Mechanisms of Life History Evolution. The Genetics and Physiology of Life History Traits and Trade-Offs. Oxford University Press, Oxford, UK. 478 pages, 75 illustrations, ISBN 978-0-19-956877-2.

Galikova, M., Klepsatel, P., Senti, G., and T. Flatt. 2011. Steroid hormone regulation of C. elegans and Drosophila aging and life history. Experimental Gerontology 46:141-147.

Flatt, T., Min, K.-J., D’Alterio, C., Villa-Cuesta, E., Cumbers, J., Lehmann, R., Jones, D.L., and M. Tatar. 2008. Drosophila germ-line modulation of insulin signaling and lifespan. Proceedings of the National Academy of Sciences USA 105:6368-6373.

Flatt, T., and D.E.L. Promislow. 2007. Physiology: still pondering an age-old question. Science 318:1255-1256.

Flatt, T., and T.J. Kawecki. 2007. Juvenile hormone as a regulator of the trade-off between reproduction and life span in Drosophila melanogaster. Evolution 61:1980-1991.

Our current research is funded by the

• Swiss National Science Foundation (SNF)
• University of Lausanne (UNIL)

In the past our research and mobility has been generously sponsored by the following funding agencies and organizations:

• Austrian Science Foundation (FWF)
• Vetmeduni Vienna
• Austrian Research Promotion Agency (FFG) and Brainpower Austria
• Swiss National Science Foundation (SNF)
• Roche Research Foundation (RRF)
• Swiss Study Foundation
• Dr. Max Husmann Foundation
• Emilia Guggenheim-Schnurr Foundation
• Vienna Graduate School of Population Genetics (funded by FWF)
• Wissenschaftskolleg zu Berlin

We encourage inquiries from well-trained and talented evolutionary and/or molecular biologists about the availability of internships, M.Sc., Ph.D. and postdoc positions. New jobs are available irregularly, depending on external and internal funding. Please contact Thomas Flatt ahead of time, i.e. 6-12 months before your intended arrival. If no current funding is available, we might encourage candidates to apply for their own fellowships in order to join the lab. When applying please send a cover letter stating your research interests and why you want to work with Thomas, a detailed CV, publications (if any), and full contact details of at least two academic referees.

Advice for Students: