The study of the molecular mechanisms involved in cellular ageing

Cellular ageing is generally defined as the progressive decline in the resistance to stress and other cellular damages, causing a gradual loss of cellular functions and resulting eventually in cell death. There are two types of cellular ageing:

  1. Replicative ageing, which refers to the limited number of divisions that a single cell can attain.
  2. Chronological ageing, which is measured in time units by determining the mean and the maximum survival time of a post-mitotic yeast population and not of single cells.

To date, the mechanisms of ageing, whether replicative or chronological, are ill-defined. Research using different genetic model organisms led to the identification of about twenty genes that can prolong the lifespan of an organism (1-6). Remarkably, studies using Caenorhabditis elegans, mouse, and yeast models revealed the existence of common pathways controlling ageing in these organisms. For instance, studies in S. cerevisiae resulted in the identification of two cellular pathways involved in the control of chronological ageing. One of them is the RAS/cAMP/PKA cascade. The other one, is based on the discovery of SCH9 gene. These pathways are involved in the regulation of the cell’s defence response against free radicals, and other reactive oxygen molecules that accumulate in the cell with time and damage macromolecules such as DNA, RNA and proteins.

Our main objective is to identify novel genes involved in the mechanisms of chronological ageing. These genes will be studied in terms of their interaction with other cellular components and their role in the pathways in which they act.

In our research, we use genetic approaches with the fission yeast Schizosaccharomyces pombe. This yeast is considered an excellent model for human physiology and cell biology because basic cellular processes such as cell division, cell cycle regulation and several signalling pathways in S. pombe are very similar to those of higher eukaryotes (7). Therefore, our studies should contribute to our understanding of the genetic mechanisms underlying the ageing processes in mammalian cells.

References :

(1) Sinclair D, Mills K, and Guarente L (1998). Aging in Saccharomyces cerevisiae. Annu Rev Microbiol. 52, 533-560.
(2) Fabrizio P and Longo VD (2003). The chronological life span of Saccharomyces cerevisiae. Aging Cell. 2,73-81.
(3) Longo VD and Finch CE (2003). Evolutionary Medicine: From Dwarf Model Systems to Healthy Centenarians? Science 299,1342-1346.
(4) Hekimi S. and Guarente L (2003). Genetics and the specificity of the aging process. Science 299, 1351-1354.
(5)Breitenbach M, Madeo F, Laun P, Heeren G, Jarolim S, Fröhlich K-U, Wissing S, and Pichova A (2003). Yeast as a model for ageing and apoptosis research. Topics Curr. Genet 3, 1-39.
(6) Jazwinski SM (2004). Growing old: metabolic control and yeast aging. FEMS Yeast Res.,119-125.
(7) Sipiczki M (2004). Fission Yeast Phylogenesis and Evolution. In : The Molecular Biology of Schizosaccharomyces pombe: Genetics, genomics and beyond. Eds R. Egel. Springer Verlag, Berlin-Heidelberg.