Researchers discover common cause for aging and age-related disease

By Wallace Ravven on May 15, 2003

Why do serious diseases such as cancer, Alzheimer’s and Huntington’s mainly hit us in
middle age or later? The links between aging and age-related diseases have proved elusive.

In studies of the powerfully informative roundworm, C. elegans, UCSF scientists have
discovered that a class of molecules found in the worms and in people can both prolong life in
the worm and prevent the harmful accumulation of abnormal proteins that cause a debilitating
Huntington’s-like disease. The finding appears to be the first evidence in an animal of a link
between aging and age-related disease.

The molecules, called “small heat-shock proteins,” are known to assemble into
complexes that bind to damaged or unfolded cellular proteins and prevent them from forming
into harmful aggregations.
“We think we’ve found an important physiological explanation for both aging and agerelated
disease,” said Cynthia Kenyon, PhD, the Herbert Boyer Professor of Biochemistry and
Biophysics at UCSF and senior author on a paper describing the work in the May 16 issue of
SCIENCE. “The question of why older people are more susceptible to so many diseases has
been a fundamental, unsolved problem in biology. Our findings suggest a beautiful molecular
explanation, at least for this protein-aggregation disease.

“By preventing damaged and unfolded proteins from aggregating, this one set of
proteins may be able to stave off both aging and age-related disease. The small heat-shock
proteins are the molecular link between the two.”

The growing roster of diseases thought to be caused by protein clumping or aggregation
—Alzheimer’s, Huntington’s, Parkinson’s, prion diseases—suggests that the small heat shock
proteins may influence the onset of many age-related ailments, the researchers say. The
pharmaceutical industry is already exploring ways to increase the activity of heat-shock
proteins. The research by Kenyon’s laboratory indicates that if these drugs work, they may not
only protect protein function, but also extend life.

Kenyon made international news 10 years ago when her laboratory showed that
modifying a single gene in C. elegans doubled the worm’s healthy life-span. The gene, known
as daf-2, encodes a receptor for insulin as well as for a hormone called insulin-like growth
factor. The same or related pathways have since been shown to affect longevity in fruit flies
and mice and are likely to control life-span in humans as well.

Why do serious diseases such as cancer, Alzheimer’s and Huntington’s mainly hit us in
middle age or later? The links between aging and age-related diseases have proved elusive.
In studies of the powerfully informative roundworm, C. elegans, UCSF scientists have
discovered that a class of molecules found in the worms and in people can both prolong life in
the worm and prevent the harmful accumulation of abnormal proteins that cause a debilitating
Huntington’s-like disease. The finding appears to be the first evidence in an animal of a link
between aging and age-related disease.

The molecules, called “small heat-shock proteins,” are known to assemble into
complexes that bind to damaged or unfolded cellular proteins and prevent them from forming
into harmful aggregations.
“We think we’ve found an important physiological explanation for both aging and agerelated
disease,” said Cynthia Kenyon, PhD, the Herbert Boyer Professor of Biochemistry and
Biophysics at UCSF and senior author on a paper describing the work in the May 16 issue of
SCIENCE. “The question of why older people are more susceptible to so many diseases has
been a fundamental, unsolved problem in biology. Our findings suggest a beautiful molecular
explanation, at least for this protein-aggregation disease.
“By preventing damaged and unfolded proteins from aggregating, this one set of
proteins may be able to stave off both aging and age-related disease. The small heat-shock
proteins are the molecular link between the two.”

The growing roster of diseases thought to be caused by protein clumping or aggregation
—Alzheimer’s, Huntington’s, Parkinson’s, prion diseases—suggests that the small heat shock
proteins may influence the onset of many age-related ailments, the researchers say. The
pharmaceutical industry is already exploring ways to increase the activity of heat-shock
proteins. The research by Kenyon’s laboratory indicates that if these drugs work, they may not
only protect protein function, but also extend life.

Kenyon made international news 10 years ago when her laboratory showed that
modifying a single gene in C. elegans doubled the worm’s healthy life-span. The gene, known
as daf-2, encodes a receptor for insulin as well as for a hormone called insulin-like growth
factor. The same or related pathways have since been shown to affect longevity in fruit flies
and mice and are likely to control life-span in humans as well.

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