Intuitively, we all know that the aging clock must reset from one generation to the next. The children of a 70 year-old man have the same life expectancy as those of a 20 year-old. But how does this happen? Is the germ-line somehow protected from aging or is age reset from one generation to the next? Budding yeast is the ideal model system to test the latter hypothesis. Budding yeast cells have a finite life-span and individual cells can be followed during the aging process. So we asked a simple question. What is the life expectancy of gametes (spores in yeast) produced by an old cell? Are they young or are they old? The result was astounding in its clarity. All four gametes generated by an aged cell show the same replicative potential as gametes generated by a young cell.
The resetting of lifespan that occurs during gametogenesis, is accompanied by the elimination of age-induced cellular damage (Figure 1 and 2) and depends on the meiosis-specific transcription factor NDT80.
Interestingly, transient induction of NDT80 extends the replicative lifespan of aged cells during vegetative growth. We are now determining the mechanisms underlying aging in yeast focusing on how nucleolar structure changes during the aging process and investigating whether it is these changes that cause a decline in proliferative potential and eventual cell death. We are also testing whether Ndt80 homologs in mammals affect the aging process. It is our hope that these studies will provide insights into the mechanisms of aging and facilitate the development of strategies for longevity.
Unal E, Kinde B, Amon A. Gametogenesis eliminates age-induced cellular damage and resets life span in yeast. Science. 2011 Jun 24; 332(6037): 1554-15547.
Unal E, Amon A. (2011). Gamete formation resets the aging clock in yeast. Cold Spring Harb Symp Quant Biol. 76:73-80.