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Scientists’ New Goal: Growing Old Without Disease
Researchers plan to test a pill to prevent or delay Alzheimer’s, heart disease and other ailments that come with age
ENLARGE
Brian Harkin for The Wall Street Journal
By
Sumathi Reddy
March 16, 2015 5:43 p.m. ET
43 COMMENTS
Some of the top researchers on aging in the country are trying to get an unusual clinical trial up and running.
They want to test a pill that could prevent or delay some of the most 
debilitating diseases of old age, including Alzheimer’s and 
cardiovascular disease. The focus of the project isn’t to prolong life, 
although that could occur, but to make the last years or decades of 
people’s lives more fulfilling by postponing the onset of many chronic 
diseases until closer to death.
The project aims to tap into the growing body of research targeting 
aging, which has revealed a half dozen or more drugs that appear to 
delay the aging process in laboratory experiments on animals and 
observational studies of people. Some of the drugs also have been found 
to reduce the incidence of chronic diseases associated with old age.
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“Aging is the major risk factor for all these diseases—heart disease, 
cancer, diabetes and Alzheimer’s,” said Nir Barzilai, director of the 
Institute for Aging Research at Albert Einstein College of Medicine in 
New York City who is leading the proposed study. “If you want to make a 
real impact you have to modulate the risk of aging and by that the risk 
for all those diseases of aging.”
ENLARGE
Dr. Barzilai expects to enroll more than 1,000 elderly participants in 
the randomized, controlled clinical trial to be conducted at multiple 
research centers and take five to seven years. The project is in the 
preliminary stages and permanent funding hasn’t yet been secured. 
Funding for the planning phase is coming from the American Federation 
for Aging Research, a nonprofit organization of which Dr. Barzilai is 
deputy scientific director.
The trial aims to test the drug metformin, a common medication often 
used to treat Type 2 diabetes, and see if it can delay or prevent other 
chronic diseases. (The project is being called Targeting/Taming Aging 
With Metformin, or TAME.) Metformin isn’t necessarily more promising 
than other drugs that have shown signs of extending life and reducing 
age-related chronic diseases. But metformin has been widely and safely 
used for more than 60 years, has very few side effects and is 
inexpensive.
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The scientists say that if TAME is a well-designed, large-scale study, 
the Food and Drug Administration might be persuaded to consider aging as
 an indication, or preventable condition, a move that could spur drug 
makers to target factors that contribute to aging.
A study that helped convince the gerontologists to pursue the TAME 
project was done in the U.K. and published last year in the journal 
Diabetes, Obesity and Metabolism. Researchers used data from a national 
registry of more than 180,000 people, comparing the treatment of 
metformin with that of sulfonylurea, another drug used for diabetes. 
They also created two control groups of nondiabetic people.
People who took metformin lived longer than those taking sulphonylurea, 
the study found. In addition, the people with diabetes who were 
71-to-75-years-old at baseline and took metformin outlived their 
nondiabetic controls with a 15% greater survival rate.
“Observational studies like this are never definitive,” said Jill 
Crandall, director of the Diabetes Clinical Trials Unit at Albert 
Einstein College of Medicine and part of the TAME planning team. “But it
 is one of the observations that certainly supports our hypothesis—that 
certain pharmacological interventions, like metformin, may have broad 
effects in improving health and increasing health span.”
Dr. Crandall also participated in a federally funded study that found 
metformin and lifestyle changes were both effective in staving off 
diabetes in people at high risk for the disease for at least 10 years. 
Data from the study, which followed more than 3,000 adults for 15 years,
 are now being analyzed to see whether long-term use of metformin 
prevented the development of cardiovascular disease, cancer, cognitive 
decline and physical-function decline. The results could help in the 
planning of the TAME study, she said.
Dr. Barzilai, who is leading the effort to test if the drug metformin 
can delay or prevent chronic diseases, also focuses in his work on the 
genetics of centenarians. ENLARGE
Dr. Barzilai, who is leading the effort to test if the drug metformin 
can delay or prevent chronic diseases, also focuses in his work on the 
genetics of centenarians. Photo: Brian Harkin for The Wall Street 
Journal
Research has found that metformin targets the chemicals produced by 
age-related senescent cells—normal cells that stop dividing and produce 
toxic substances damaging to the cells around them, said James Kirkland,
 director of the Robert and Arlene Kogod Center on Aging at the Mayo 
Clinic in Rochester, Minn., and part of the TAME planning team. 
Senescent cells usually develop as people age or at sites of age-related
 chronic diseases, such as the brain in Alzheimer’s patients or around 
the plaques that lead to heart attacks and strokes, he said. It isn’t 
proven if senescent cells actually cause the disease.
Metformin appears also to slow the development of age-related symptoms 
by increasing the enzyme AMP kinase, which normally declines with age, 
and decreasing the protein mTOR, which helps to regulate cell growth.
Several other drugs also have shown life-extension properties in mice 
and in laboratory work, Dr. Kirkland said. His research group last week 
published a study on mice in the journal Aging Cell which showed that a 
combination of two drugs—dasatinib, a cancer drug, and quercetin, a 
supplement that can be found in health food stores—were potentially 
effective.
“There’s more and more evidence that by targeting aging itself we might 
be able to target these age-related chronic diseases that have been so 
intractable for us to try to come up with a cure for,” Dr. Kirkland 
said.
Fighting each major disease of old age separately isn’t winnable, said 
S. Jay Olshansky, another TAME project planner and a professor at the 
school of public health at the University of Illinois at Chicago. “We 
lower the risk of heart disease, somebody lives long enough to get 
cancer. If we reduce the risk of cancer, somebody lives long enough to 
get Alzheimer’s disease.”
“We are suggesting that the time has arrived to attack them all by going
 after the biological process of aging,” Dr. Olshansky said.
Sandy Walsh, an FDA spokeswoman, said the agency’s perspective has long 
been that “aging” isn’t a disease. “We clearly have approved drugs that 
treat consequences of aging,” she said. Although the FDA currently is 
inclined to treat diseases prevalent in older people as separate medical
 conditions, “if someone in the drug-development industry found 
something that treated all of these, we might revisit our thinking.”
Other experts agree with the goal of delaying chronic disease for the 
elderly, but question whether medication is the best way to do that. “I 
can certainly see how medicine can play a role if it turns out this 
study shows some promising findings,” said Alicia Arbaje, a geriatrician
 and an assistant professor of medicine at Johns Hopkins School of 
Medicine. “But aging is very complex and it’s probably going to take a 
multifaceted approach to help people delay or ensure that they age in a 
healthy way,” said Dr. Arbaje, who isn’t affiliated with the TAME trial 
planning.
Effective interventions to delay aging already exist, Dr. Arbaje noted, 
such as exercise, nutrition, social engagement, stress reduction and 
getting adequate sleep. “These are reliable and effective ways to keep 
people healthy as they age,” she said. “The problem is they’re not as 
easy as taking a medication.”
Write to Sumathi Reddy at sumathi.reddy@wsj.com
 
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