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Yeast may hold secret to cancer and ageing
Short-termism blamed for innovation dearth
Skin become battleground
Ageing
Yeast may hold secret to cancer
and ageing
Humans cells are like yeast cells
– their ability to copy their genes accurately gets worse from middle
age, and this might cause cancer, reports today’s issue of Science.
Dr Daniel Gottschling and Michael
McMurray, scientists at Fred Hutchinson Cancer Research Centre in the US,
have found striking similarities between humans and simple baker's yeast
with regard to the changes their genes undergo as they age. "While
yeast don't get cancer, they do have one of the major hallmarks of
malignancy, which is genetic instability," Gottschling said. "We
found a similar thing in yeast that has been seen in humans: genetic
instability shoots up dramatically in the middle to late stage of
life."
When yeast cells hit the equivalent
of late-middle age, the Fred Hutchinson researchers discovered they
experience a sudden 200-fold surge in the production of genetic changes
typically manifested as loss of heterozygosity, or LOH, a condition
characterised by missing or mutated chromosomes. This finding suggests
that the yeast Saccharomyces cerevisiae, a simple, single-celled
organism, may be an ideal model for understanding age-related cancer
development in humans.
"Yeast gives us, for the first
time, the potential for not only understanding the principles of what's
going on mechanistically but also which molecules might be relevant to the
process of age-related cancer development," said Gottschling.
The American Cancer Society reports
nearly 80% of cancers are diagnosed after age 55. After reaching
late-middle age, men face a 50% chance of developing cancer and women have
a 35% chance.
Gottschling and Murray found most
yeast cells survive for about 30 or 35 generations of cell division. Each
generation is represented by a mother cell's production of a new daughter
cell, or yeast bud. The yeast cells were genetically manipulated to change
colour if they started showing genetic instability. In every strain of
yeast studied, genetic mistakes started happening at the equivalent of
late-middle age.
"We found it takes about 25
generations, or cell divisions, to see an LOH event," Gottschling
said. "After that, the genetic instability just starts happening like
crazy. We think a switch of some kind is being thrown, because it's
happening in virtually all of the new offspring at the same time."
Even among the longest-lived yeast
that were genetically manipulated to go through 50 to 60 generations of
cell division before dying, the evidence of DNA damage surfaced, like
clockwork, right around the 25th generation. "This tells us that life
span operates on its own clock; it is independent of genetic instability.
Living longer doesn't necessarily mean you have fewer genetic mistakes. It
just means you somehow live longer with more of them," Gottschling
said.
As such, the researchers believe
that genetic instability is related not to how close cells are to death,
but how far they are from birth, i.e. how many times they've divided.
The fact that aging mother cells
are protected from age-induced genetic instability also has evolutionary
implications, McMurray said. "In yeast genetics, people historically
have thought of the mother cell as being the trash bin that accumulates
all the genetic bad stuff so that the daughters could be protected. But we
found the opposite. The mother remains protected, which preserves her
chance to produce more normal daughters."
If this evolutionary process is
biologically conserved in human stem cells, Gottschling said, "It
could explain a lot of the age-induced diseases that happen in
people."
So if cancer is an inherent
consequence of aging, are lifestyle interventions to prevent the disease
-- such as eating right, not smoking and getting enough physical activity
-- merely an exercise in futility?
"People should still keep
eating their broccoli," Gottschling said. "Our yeast were on a
diet equivalent to steak and potatoes. We had the mother cells growing in
a very rich, nutrient-dense environment. They were, in essence, pigging
out the whole time. We'd like to do similar experiments in which we put
the yeast on a 'lean and mean' diet to see if we could delay the switch
that triggers the genetic instability," he said. "Yeast promises
to be an excellent model system for testing various environmental factors,
such as caloric restriction, to get at the mechanisms of cancer
initiation."
Innovation
Short-termism blamed for
innovation dearth
The idea that invention is valuable
only when it results in a product is wrong, former Microsoft chief
technology officer Nathan Myhrvold said in a keynote speech to the
Emerging Technologies conference at MIT this week.
Myhrvold, current managing director
of Intellectual Ventures, compared the software business in the 1970s and
80s with views today. Conventional wisdom, he said, held that there was no
money to be made in the software business—that software had value as a
product only when it was bundled with something more “real”—that is,
hardware. Today’s conventional wisdom applies that same erroneous
principle to invention: invention is valuable, but only when it is bundled
with real products.
“Invention is the next
software,” Myhrvold said, a reference to the exponential growth and
value increases that it has wrought. But he warned the practice of
invention is under tremendous pressure and occupies a far lower funding
priority in companies and in government than it should. This is a critical
error, he said. Corporate research houses such as Lucent Technologies’
Bell Labs and IBM’s Watson Research, homes to a dozen Nobel Prize
winners, are now focused on short-term gains with an impact on existing
products. “These research houses are shadows of their former selves,”
Myhrvold asserted. “In these big companies, you don’t invent. Most
engineers are paid not to invent,” he said. Similarly, these days
universities are less about invention than education or contracted
research. “You can be a tenured professor at MIT without having invented
anything,” Myhrvold said.
He believes the next advances will
come from genomics and nanotechnology. Both are ripe: there is high
consumer demand for improvements and innovation, intellectual depth, and
working proofs-of-concept. He warned that nanotechnology is over-hyped and
under-delivering. “It’s a few breakthroughs short right now,” he
said.
*MIT’s Technology Review magazine
named Combinatorx president and chief executive Alexis Borisy as its
Innovator of the Year for his work in screening and developing combination
drugs that target multiple pathways involved in a disease. The company has
a pipeline of clinical and pre-clinical products including treatments in
development for cancer and rheumatoid arthritis and has ongoing research
in respiratory, metabolic and infectious diseases.
Markets
Skin become battleground
Traditional skin care firms are
under threat from brands from dermatologists, says a new study from market
researcher Kline & Company.
“Dermatologist brands represent a
growing concern to established marketers," said Lenka Contreras,
group director of Kline's consumer products practice. "As these new
dermatologist brands become more publicised and more widely distributed,
traditional skin care marketers are countering with new products with a
high-end, therapeutic positioning."
Contreras adds firm such as Procter
& Gamble and Avon are reacting to the growing availability and desire
for more affordable dermatological services.
"With their recent
introductions Olay Regenerist and Avon Clinical, these companies are
trying to recapture or protect market share from not only professional and
dermatologist brands but also medical treatments like Botox," she
says.
Estee Lauder has even formed a
partnership with dermatologists Kathy Fields and Katie Rodan, the brains
behind Multi-Med and Proactiv. Lauder has also signed on Dr Karen Grossman
as a spokesperson for Prescriptives' new at-home microdermabrasion
products. The veteran acne fighter Clearasil is getting a boost of its own
through the backing of dermatologist Laurie Polis, while Neutrogena is
featuring a "dermatologist- recommended" tagline in ads.
"These traditional marketers
are trying to disarm the dermatologist brands by beating them at their own
game," says Contreras, "and the professional skin care brands
are now seeing competition from both sides."
Over the past five years, day spas,
destination spas, dermatologists, and other medical care providers have
become a highly visible force to meet and influence consumer skin care
needs. These facilities provide a variety of treatments, from facials to
Botox injections. A hybrid facility, the medi-spa, emerged in 2002 as the
latest venue that is physician-based but also focuses on cosmetic invasive
and non-invasive skin care treatments. Kline says that by 2004 there will
be about 700 such venues in the US, with strong growth expected in the
near future.
Not only are consumers flocking to
these skin care havens for treatments, they are also buying the take-home
kits to extend the effects of the treatment.
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