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Health // Doctor in the House
MidWeek Staff

Revolutionary Study On Aging

Drs. Kamal Masaki And Bradley Willcox
Researchers at Kuakini Medical Center and John A. Burns School of Medicine

Where did you receive your schooling/training?

Dr. Masaki: I graduated from medical school in India at the University of Bombay. I did internal medicine residency training at Michigan State University and geriatric medicine fellowship training at the University of Hawaii. I have been in practice for 22 years. Dr. Willcox and I are both researchers at Kuakini Medical Center and professors of geriatric medicine at the John A. Burns School of Medicine.

Dr. Willcox: I attended medical school at the University of Toronto, and I did my internal medicine residency at the Mayo Clinic in Minnesota, and then a geriatrics fellowship at Harvard Medical School in Boston. I have been in practice for 11 years.

As Director of Research for Kuakini Medical Center, what are some of the studies you are involved with?

Dr. Masaki: The most famous study is the Kuakini Honolulu Heart Program. It started in 1965 with more than 8,000 American men of Japanese ancestry. At that time they were middle-aged. We’ve followed them ever since with regular medical exams, so they have been followed for 48 years. It’s one of the longest-running studies in the world.

What was the purpose of the study?

Dr. Masaki: The original purpose was to study genetic and environmental factors associated with heart disease and stroke. Many of the things that are common knowledge now – like smoking being bad for you, watching your diet and your cholesterol and taking care of your blood pressure and diabetes – many of these things we take for granted now are a result of the Kuakini Honolulu Heart Program and other studies like it.

How long is the study expected to continue?

Dr. Masaki: We will continue until all of the research participants have passed away. Currently we have fewer than 300 men alive. Our youngest man is now 95 years old and the oldest is 105. For the past 22 years the focus has shifted. We still look at heart disease and stroke, but now we have added studies of other diseases of aging such as dementia, Alzheimer’s disease, disability and depression, even mechanisms of aging itself and healthy aging and longevity.

What were some of your findings?

Dr. Masaki: We found that things you do in midlife can really affect your health in old age. For example, we found that if high blood pressure is left untreated in midlife, it causes a higher risk of having memory problems in late life. You can see the negative effects 25 years later. Dr. Willcox has been studying longevity and healthy aging.

Dr. Willcox: There are quite a few ancillary studies from the original Kuakini Honolulu Heart Program studies – at least four large ones and many smaller ones. Two of the studies we’re working on right now are the Kuakini Hawaii Lifespan Study and the Kuakini Hawaii Healthspan Study. The Lifespan Study’s goal is to try to understand mechanisms of healthy aging, because it’s difficult to define what healthy aging is. We came up with a definition based on a popular definition in geriatrics, which was successfully avoiding disease and disability, and trying to be active and engaged with life. We measured major diseases as well as cognitive and physical disabilities at an important time in life, from age 45 to over 100 years. We have data on what are the risk and protective factors that allow people to stay healthy throughout those years.

One study that we published in the Journal of the American Medical Association in 2006 shows that if you avoid common risk factors in middle age – we measured nine for this study – you have up to six times the odds of living to be 90 years old in good health. We’re just finishing up a study right now where we’re looking to see if the same factors still hold in late life, when the men were in their 70s and 80s. Those relations still hold, but with a slightly different set of risk factors in older age. In midlife, we were looking at things like triglyceride levels and being overweight, and smoking. At older age, inflammation becomes a lot more important.

Now, we’re not only trying to understand what modifiable factors are important, but through what biological pathways these factors work. What are the genes involved? We discovered one gene where if you have one of these “protective” genes from your mom or dad, you have double the odds of living to be 100 years, and if you have two, you have triple the odds. If we can understand how that gene works biologically, maybe we can design interventions to help people age more healthfully.

Why Asian men?

Dr. Masaki: In the 1950s and early ’60s, researchers noticed that there were much higher rates of stroke and much lower rates of heart disease in Japan, compared to the United States. It started with a comparison of three groups of men of Japanese ancestry, as the NiHonSan study: Nippon in Hiroshima, Hon for Honolulu (the Kuakini Honolulu Heart Program), San for San Francisco. Hiroshima and Honolulu have continued following their cohorts for almost 50 years. The San Francisco study lasted less than a decade. Researchers compared the rates of heart disease and stroke in these three groups because they all were similar genetically – all of Japanese ancestry and all male. They found that their original hypothesis was true: Men in Japan had the lowest rates of heart disease, men in San Francisco had the highest and Hawaii was in between. Stroke was the opposite – Japan had the highest rate, San Francisco had the lowest and Hawaii was in between. This study showed that these risks were not just genetic. There were a lot of environmental factors involved in these diseases. As people moved to a different environment, their diet and lifestyle changed and this affected their disease risk.

Women weren’t included because, in those days, it was thought women don’t have heart disease, particularly Japanese women. That was almost 50 years ago before we knew that women got just as much heart disease as men but at later ages.

Moving forward, Kuakini has started an Offspring Study with sons and daughters of the Kuakini Honolulu Heart Program, looking for things that run in families.

Anything else you’d like to mention about the study?

Dr. Masaki: Our lifestyles really have an effect on health and disease. We have the genes we’re born with, but the things we do make a big difference. For example, if you avoid smoking, take care of your blood pressure and diabetes, exercise and eat well, it can make a huge difference.

Dr. Willcox: Hawaii has the longest life expectancy in the country, so it’s appropriate that we have one of the best studies of aging in the country and that we’re actively finding answers to the problems of an aging America.

Dr. Masaki: There have been more than 500 publications related to the Kuakini Honolulu Heart Program. It has really contributed to our knowledge of diseases and health in the world.

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