age, our bodies break down. One explanation for this is that oxidation from the
constant chemical reactions in our bodies eventually causes our cells to rust,
just like old metal. But geneticist Stuart Kim of Stanford University has
another explanation: an imbalance between cell proteins, which control the
transfer of genetic information. These so-called transcription factors bind to
DNA. Those that turn genes "on" are called activators and repressors
turn genes "off."
and his colleagues studied how aging in worms affects transcription factors,
especially one activator and two repressors that control the development of the
intestine and skin. He found that in the young worm, a balance of these
transcription factors is critical to the development of the skin and intestine.
As the worms aged, the repressors increase in concentration and eventually
turned down the activator. So, the genes that were supposed to be
"on" were turned "off."
says this means that "the intestine no longer functions very well and the
skin no longer functions very well, and that was contributing to why the worms
were dying at two weeks."
back the genetic clock
Kim restored the balance between the activator and the repressors, the worms
lived 50 percent longer. He suspects that many additional proteins are involved
in aging, and proper control of them could extend a worm's life even more.
why do these transcription factors become unbalanced? Kim says there is no way
to answer this from an evolutionary perspective.
usually live only five days in the wild before getting eaten by a predator.
Kim's investigations happen much later, near day 18. Kim notes, "for worms
the whole game is to try and be the fittest healthiest worm but for five
days-make as many babies as you can in five days." So the age-related
deterioration occurs only when worms are grown in the lab, free of predators.
"So everything we're looking at has not been seen by nature."
points out his findings do not imply that molecular damage is not contributing
to aging, but they do raise questions about how much of an impact that damage
has on our life span. While worms live only two weeks in the lab, flies live
two months and mice live two years. Humans share 99% of their DNA sequence with
chimpanzees but live about 40 years longer. Whales can live as long as 200
years and clams can live for 400 years.
damage common to all species
explains that in such a wide variation in life span, the molecular damage is
identical. Similar reactions occur in humans, whales, and mice. Kim asks,
"If molecular damage was driving life span and aging, why is it occurring
at such different time scales across different animals?"
transcription factors in the worms do not have an obvious human equivalent.
Yet, Kim says his work represents a conceptual change in how we think about
study appears in the July 25th edition of the journal Cell.