Is aging a disease? It is to scientists who compare normally aging animals to longer-living
As this ScienCentral News video reports, geneticists are using new high-tech
tools to study these animals to identify genes that may cause aging.
Aging and disease
It's well known that mice that live on calorie-restricted diets are good models
of health. If aging itself is a disease, those mice don't have it.
"The only thing that's known to retard the aging process is
restriction," says geneticist Tomas
Prolla. "It's the best system that we have in trying to understand
what causes aging and how to retard it."
Numerous studies of mice
and rats, model organisms like flies,
and yeast, and even a recent
study of dogs have confirmed that caloric restriction (also known as "CR")
works. Figuring out how it works at the genetic level, and developing drugs
that can mimic CR, is a goal of Prolla's research.
Prolla and his colleagues use the new technology of DNA microarrays—known
—to analyze the role of gene expression in animal aging. Scientists say a gene
is "expressed" when a cell's machinery follows the gene's DNA instructions
to make a product. Gene chips can monitor this process for thousands of genes
at a time.
Prolla's group compares gene expression in normally aging mice with that of
the longer-living CR mice. The differences in gene expression allow them to
implicate genes that likely control aging. They have done gene chip studies
of aging in skeletal
muscle, the brain,
and most recently, the heart. That
study, published in Proceedings of the National Academy of Sciences,
identified a number of genes that likely contribute to heart aging. "Once
we have identified these genes," says Prolla, "then we can ask the
question, ‘If we design a drug to manipulate the expression of these genes,
or the activity of the proteins that they encode, do they have an impact on
Aging = disease?
"We also saw that with normal aging, there are changes in the heart that
are similar in terms of gene expression to what one sees in diseases of the
heart such as heart failure," Prolla says. "So our study suggests
that a part of normal aging might be changes in the heart that predispose to
these diseases which are age-related."
Among those changes with aging are "major metabolic alterations."
For example, he says, "the heart of an embryo uses mainly carbohydrates
as an energy source, and then it shifts to fatty acids in the adult animal.
But with aging, there is a reversal such that the heart starts using carbohydrates
again as one of the main energy sources. We don’t know why that happens
with aging but that has been reported to happen also in heart failure."
Indeed, the more geneticists study aging, the more it seems that aging and
the diseases associated with it are one and the same. "Most diseases are
age-related… you basically don’t see them in young people,"
says Prolla. "If you want to, for example, prevent heart disease, prevent
cancer and prevent neurodegenerative diseases such as Alzheimer’s or Parkinson’s
disease—the only way to reduce these diseases dramatically is through interventions
that have an impact on the aging process, because these diseases are all secondary
to the aging process."
Prolla says "gene expression profiling," as he calls these studies,
can also be used to test possible interventions to retard aging and age-related
disease. "Changes in gene expression with aging… can be used as a
biological clock in a sense," he says. Monitoring those changes provides
a way to monitor whether the aging process is occurring at the regular rate,
a slower rate or even at an accelerated rate. "So what this allows us to
do is test whether specific interventions are retarding the aging process at
the molecular level."
Prolla and the University of Wisconsin have also started up a company called
Technologies, with the goal of building "the world's largest database"
of gene expression changes associated with aging, caloric restriction and other
interventions like drugs and so-called neutraceuticals.
But even if a drug being tested today can extend lifespan, it won't hit the
market for at least a long lifetime, after clinical trials could prove its effectiveness.
"For a doctor to prescribe a drug to retard the aging process in, let’s
say, an FDA-approved manner," says Prolla, "that would take more than
100 years from now because of the fact that a trial needs to be done."
Of course, Prolla says, we can improve our odds of living long, healthy lives
right now by cutting our own calories. "If someone wants to retard their
aging process and greatly improve health, we already have a way to do it, and
it’s simply caloric
restriction," he says.
Even small changes in our eating habits can be beneficial, he adds. "Given
all the research that we have done… I try not to overeat," he says.
"I don’t do any dramatic calorie restriction, but, for example, if
I’m going, let’s say, to take my daughter to eat an ice-cream, I
always ask for the smallest ice cream possible—like the kid's size."
He also suggests simply cutting out fat. "Fat has much more calories than
carbohydrates, so if you eat a lot of fat, you're going to automatically be
having a higher calorie intake" says Prolla. "So there's a number
of simple steps that a person can take to reduce somewhat their calorie intake
without any major lifestyle changes."
Prolla's research is funded by the National
Institutes of Health and the National