Closing the Generation Gap
Authors: Beckman Mary 
Published: August 2003

Imagine a mother giving birth to a baby who's as old as she is. Researchers have now found a yeast mutation that does just that: Daughter cells that sprout from these deviant fungi live only as long as their mothers do. The newborn oldsters apparently lack some or all of their mitochondria. The work might help researchers understand how yeast--and possibly stem cells--age.

Single cells of the beer-and-bread yeast
Saccharomyces cerevisiae
procreate by dividing in two. Unlike bacteria, which split down the middle, a mother yeast cell puffs out a bud that pinches off to form a daughter cell. After 20 or more generations, depending on the strain, the mother cell dies. Researchers have wondered how each new daughter has the potential for a full life-span.

To probe this question, Lai and colleagues subjected yeast to a chemical mutagen and screened for colonies with shortened life-spans at high temperatures. One strain behaved normally at a balmy 30°C but died after 5 days at a sweltering 37°C. These yeast carried a mutation in the gene for ATP2, a component of the energy-production machinery in mitochondria; presumably, the higher temperature inactivates this protein. The team tested two hypotheses for the shortened life-span. The daughter cells could be born old in some way; if so, daughters that started out with a disabled ATP2 protein would have a short life-span even if they manufactured normal ATP2 later. Alternatively, daughters could be born young but with cellular components that are mangled due to tainted ATP2. If this were the case, daughters born at high temperatures but then raised at low temperatures--where they regain operational ATP2--could recover by manufacturing the proper goods themselves.

The team grew normal and mutant yeast at high temperatures and collected the seventh daughter cells budded by the mothers. The researchers then moved the cells to 30°C and measured life-span by counting the number of times they budded. Normal yeast outlived their mothers by at least four generations. The mutant daughters, however, lasted only as long as their mothers did, indicating that the mutation had caused mothers to generate old buds. The early deaths were not due to shrinking telomeres or abnormal accumulation of rDNA circles, characteristics known to regulate yeast life-span. Additional analysis suggested that ATP2-defective mothers gave budding daughters too few, sometimes sickly, mitochondria, suggesting that mothers might bequeath youth to their offspring by providing dowries of healthy mitochondria.

The work is a "successful foray" into studying daughter life-spans directly, says molecular geneticist John Aris of the University of Florida in Gainesville. The ability to assess the age of daughters at birth will help researchers pick apart the molecular basis of yeast aging, he adds. Fungal longevity might offer insights into human biology as well. Older stem cells lose the ability to divide asymmetrically, which "may be happening through a similar mechanism as described here," says stem cell biologist Gary Van Zant of the University of Kentucky in Lexington. As many therapists already know, the baggage that daughters inherit from their mothers can influence their quality of life.

--Mary Beckman

C.-Y. Lai, E. Jaruga, C. Borghouts, S. M. Jazwinski, A mutation in the
ATP2
gene abrogates the age asymmetry between mother and daughter cells of the yeast
Saccharomyces cerevisiae
.
Genetics
162
, 73-87 (2002).
[Abstract]
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