Starving Yourself to Vastly Extended Life Span
Suggested by Recent Study
Report 10-fold life span extension in
simple organism – baker’s yeast
June 4, 2008 - Biologists have created baker’s
yeast capable of living to 800 in yeast years without apparent side
effects and this may suggest strategies for helping humans live
healthier and longer. The basic but important discovery, achieved
through a combination of dietary and genetic changes, brings science
closer to controlling the survival and health of the unit of all living
systems: the cell.
“We’re setting the foundation for reprogramming
healthy life,” said study leader Valter Longo of the University of
Southern California.
Longo’s group put baker’s yeast on a
calorie-restricted diet and knocked out two genes, RAS2 and SCH9, that
promote aging in yeast and cancer in humans.
“We got a 10-fold life span extension that is, I
think, the longest one that has ever been achieved in any organism,”
Longo said.
In 2005, the same research group reported a
five-fold life span extension in the journal Cell. Normal yeast
organisms live about a week.
“I would say 10-fold is pretty significant,” said
Anna McCormick, chief of the genetics and cell biology branch at the
National Institute on Aging and Longo’s program officer.
The NIA funds such research in the hope of
extending healthy life span in humans through the development of drugs
that mimic the life-prolonging techniques used by Longo and others,
McCormick added.
Baker’s yeast is one of the most studied and best
understood organisms at the molecular and genetic level. Remarkably in
light of its simplicity, yeast has led to the discovery of some of the
most important genes and pathways regulating aging and disease in mice
and other mammals.
The study appeared in the Jan. 25, 2008, issue of
the journal PLOS Genetics. A companion study, showing that the same
genetic changes in yeast reverse the course of an accelerated aging
syndrome, appears in the Jan. 14 issue of the Journal of Cell Biology.
A study recently published in Cell (Issue 130,
pages 247-258, 2007) reported that a mouse with a gene mutation first
identified by Longo’s group lived 30 percent longer than normal and also
was protected against heart and bone diseases without apparent side
effects.
Longo’s group next plans to further investigate
life span extension in mice, and also is studying a human population in
Ecuador with mutations analogous to those described in yeast.
“People with two copies of the mutations have very
small stature and other defects,” he said. “We are now identifying the
relatives with only one copy of the mutation, who are apparently normal.
We hope that they will show a reduced incidence of diseases and an
extended life span.”
Longo cautioned that, as in the Ecuador case,
longevity mutations tend to come with severe growth deficits and other
health problems. Finding drugs to extend the human life span without
side effects will not be easy, he said.
An easier goal, Longo added, would be to use the
knowledge gained about life span “in a fairly limited way, to reprogram
disease prevention.”
In the study appearing in the Jan. 14 Journal of
Cell Biology, Longo’s group developed a yeast model for human
Werner/Bloom syndromes, incurable diseases that prematurely age,
increase cancer incidence and eventually kill their victims.
The same mutations that play a central role in the
10-fold life span extension reversed the premature aging process, the
researchers found.
Longo suggested that although a very simple system
was used in his studies, existing drugs targeting analogous anti-aging
pathways in humans – specifically the pathway involving Insulin Growth
Factor, or IGF-1 – should be considered for testing on Werner/Bloom
patients.
“Maybe it will do nothing, but having nothing else,
I think it’s certainly a good thing to try,” Longo said.
In the PLOS Genetics study, Longo’s group
identified a major overlap between the genes previously implicated in
life span regulation for yeast and mammals and those involved in life
span extension under calorie restriction.
“We identified three transcription factors … that
are very important for the effect of calorie restriction, but at the
same time, we also showed that it’s not enough because even without
these transcription factors, calorie restriction can still extend life
span a little bit,” Longo said.
“So that means that we’ve identified a lot of the
key players in the calorie restriction effect but not all of them.”
Calorie restriction – in practice, controlled
starvation – has long been shown to reduce disease and extend life span
in species from yeast to mice.
Scientists believe that a nutrient shortage kicks
organisms into a maintenance mode, enabling them to re-direct energy
from growth and reproduction into anti-aging systems until the time they
can feed and breed again.
Calorie restriction is now being tested by other
researchers on primates and even humans, Longo said.
Longo has been studying aging at the cellular level
for 15 years and has published articles in the nation’s leading
scientific journals. His laboratory developed a simple and inexpensive
method for measuring the true chronological life span of yeast.
Previously, scientists used the number of a yeast cell’s offspring as a
proxy for its age.
The so-called replicative life span technique
remains in use, and the NIA’s McCormick said that Longo’s method was
controversial at first. However, she said, the scientific community now
appears to accept its usefulness. She said Longo’s “stationary phase”
method is particularly applicable to studies of cells that do not divide
for most of their life, such as those in the brain or in muscle.
“Stationary phase I think of as normal cell
survival,” McCormick said. She added that NIA funds both stationary
phase and replicative life span research.
Editor’s Notes:
Longo is the Albert L. and Madelyne G. Hanson
Family Trust Associate Professor in Gerontology with a joint appointment
as associate professor of biological sciences at USC College. A native
of Italy, Longo came to the United States to study jazz performance but
switched his major to biochemistry as an undergraduate at the University
of North Texas. He earned his Ph.D. in biochemistry from UCLA in 1997
and completed his postdoctoral training in neurobiology at USC.
The studies were funded by NIA (part of the
National Institutes on Health) and the American Federation for Aging
Research.
USC graduate students Min Wei and Paola Fabrizio
were first authors on the PLOS Genetics paper. USC graduate students
Federica Madia and Cristina Gattazzo were first authors on the Journal
of Cell Biology paper. The other members of Longo’s group were USC
graduate students Abdoulaye Galbani, Jesse Smith, Christopher Nguyen,
Selina Huey, Lucio Comai, Jia Hu, Huanying Ge and Chao Cheng, USC
computational biologist Lei Li, and William Burhans and Martin
Weinberger of the Roswell Park Cancer Institute in Buffalo, N.Y.
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