Rethinking Healthy Aging

By Rita Beamish

There was a time when menopausal hormone therapy was seen as a near-panacea for the ills of the aging woman. That was before Marcia Stefanick and her Women's Health Initiative (WHI) colleagues put the theory to the test and upended the medical world.

Now Stefanick is on a different quest, but this time she's not expecting to disprove a widely-held myth as she did with the assumed benefits of hormone therapy in the WHI. Instead, she hopes to provide scientific underpinning to something widely believed – that exercise prolongs life and in particular sustains cardiovascular health.

"Why do some women do so well, while others age less successfully?" the professor of medicine and leader of women's health and sex differences research at Stanford asks. "The aging of the cardiovascular system is the main question."

Stefanick  has always been interested in questions of "successful aging," along with her work on heart health and sex hormones.  The daughter of a Pennsylvania veterinarian, Stefanick grew up with four brothers and two sisters "in a sexist era where girls do this and boys do that."  She developed  an intrinsic interest in the differences between the sexes. After more than two decades conducting a series of hormone studies, including the blockbuster National Institutes of Health (NIH)-funded WHI, she is looking more broadly at aging.  She continues work on non-hormone – and less publicized — aspects of the WHI, which started with nearly 162,000 women subjects aged 50-79 in 1993. In these studies, Stefanick  is looking at the aging characteristics of women, including physical and mental function, plus cardiovascular health, cancer and osteoporosis.

Stefanick seeks to know what, regardless of hormone use, predicts successful aging. Her search to date has involved diet, quality of life, stress measures,  and sleep patterns in WHI women, now aged 65 to 95, and also 6,000 men, aged 75 and older, who are enrolled in the so-called MrOS study  of osteoporotic fractures.  Delving deeper into the body's response to aging, Stefanick's team now is looking also at loss of skeletal muscle and changes in body fat.

Her newest proposal to the NIH seeks to get to the bottom of how exercise – or lack of it — affects the aging body. The project involves more than 93,000 women with a mean age of 78, and harkens back to Stefanick's  doctoral, postdoctoral and research associate days at Stanford. Back then, she conducted human exercise studies with Peter Wood, her marathon partner and Stanford mentor who helped her see a path beyond her abhorrence of animal research, which had nearly caused her to drop out of graduate school.

Stefanick believes the new research will be "the best study of aging women that exists." In particular, she expects it to bear out the benefits of exercise.

"I personally think the most important intervention for reducing morbidity and mortality and maintaining physical and cognitive function is physical activity," she said.

Research already links exercise to positive effects on blood pressure, heart rate and cholesterol numbers. So what's the need for a new study?

"All the data support that belief – but science requires a higher level of evidence,"  Stefanick said.  "Actual proof is needed to show that increased activity and decreased sedentary behavior lead to improved aging."

“Women who exercise on their own may by physiologically different from women who don't exercise, so we don't know that their exercise caused the improved health they experience. The question we hope to answer is – do we really need to promote exercise in the population? Does exercise truly benefit the most older women?"  Stefanick said.

To bolster a case for medically recommending physical activity, she said, "We need a large trial that randomly assigns women to exercise or control groups that we can study."

Participants will be assigned specific daily exercise routines – mostly walking, strength training, balance and flexibility. Stefanick and her team will determine actual health outcomes, particularly heart disease and stroke, but also cancer, osteoporotic fractures, and quality of life. A sedentary group will provide comparison.

Stefanick firmly expects exercise to prove itself.

"If we're successful, if we prove physical activity works, people will say, duh, we already knew that, but the reality is we don't know it, and that's the issue," she said.