The computer industry uses version numbers to track the evolution of software. The first release after trial versions is called version 1.0. Major changes are reflected in the first digit of the version number, as in version 2.0. Any minor changes are reflected in the second digit, as in version 2.1. I’ve recently realized that this labeling scheme could apply to hormones as well. Think of it this way – each decade, along with its associated hormonal changes, is a major version change.
In the midst of writing about Alzheimer’s and dementia, I find myself in Hormones 4.9. So far, the transition into middle-aged versions is reflected more in my mental preoccupations than in any physical manifestations. All I think about is aging and dementia.
These topics dominate my conversations now, partly because most of my friends are somewhere near Version 5.0. My colleague Rebekah and I used to talk about technical specifications and industry gossip. But when she called me from Kansas City the other day, my favorite subjects came up. She was driving her dog Max to his acupuncturist appointment, for treatment of arthritis and irritable bowel syndrome. I told her about my scheme for labeling hormonal stages, and we wondered how it would work for dogs.
Then she told me her father-in-law had fallen at the nursing home. “Nine stitches and a bump the size of a prairie chicken egg,” she said. “I went to visit him yesterday, and said ‘That was really a nasty fall.’ ‘Fall!’ he said, ‘I didn’t fall – I was taken down by a mob in the bathroom! Then the lady who sits on people at football games got me….”
With a sense of humor and an occasional glass of wine, I figure we can handle Hormones 5.0. But I’m more worried about 6.0 and beyond. It seems no one is immune to serious problems such as Alzheimer’s, cancer, and heart disease. Maybe this is why when Gail Rae Hudson (The Mom and Me Journals) and her mother watched the movie Cocoon recently, they decided they would drink from the fountain of youth if they had the chance.
I thought of them when I watched 10 Years Younger yesterday [I had turned on the television for research purposes – really!]. During the program, image experts succeeded in moving a woman’s appearance from Hormones 4.9 back to Hormones 3.9 or so. But what good is looking like Version 3.9 if I can’t remember where I left my car?
Is there anything we can do to decrease our actual version numbers and avoid serious health problems? As far as I can tell, scientists don’t understand aging very well. The most popular idea about why we age is called the Free Radical Theory on Aging. According to this theory, breathing in air allows unstable molecules called oxygen free-radicals to build up in the body. These oxygen free-radicals then combine with other molecules, causing cell damage in a process similar to the way rust damages metal.
Researchers have shown that calorie restriction in mice and other organisms extends their lifespans. Fans of the Free Radical Theory think this may be because reducing food intake decreases the rate of metabolism and thus oxygen intake, and so the amount of free-radicals accumulating in the body also goes down. Some studies have contradicted this hypothesis, though. Even more discouraging, the anti-oxidant vitamins I thought might keep me in the equivalent of Hormones 4.9 for a few more years may not be effective. Maybe the Free Radical Theory of Aging won’t lead to Gail’s fountain of youth.
But Dr. Craig Atwood at the University of Wisconsin thinks a theory called the Reproductive-Cell Cycle Theory of Aging may eventually show the way. As discussed in an earlier post, he believes the same theory explains the chain of events leading to Alzheimer’s disease.
Dr. Atwood’s 2004 paper “Living and Dying for Sex: A Theory of Aging Based on the Modulation of Cell Cycle Signaling by Reproductive Hormones,” explains how calorie restriction might extend lifespans a bit differently than free radical [theorists, proponents]. The paper was co-authored by Dr. Richard Bowen of Voyager Pharmaceutical Corporation and published in Gerontology in 2004. It outlines the idea that when estrogen and testosterone levels go down in mid-life, the body cranks up other hormones (luteinizing hormone and follicle stimulating hormone, for example) in an attempt to maintain fertility.
“The increased levels of luteinizing hormone and follicle stimulating hormone signal bone, muscle, brain and other cells to divide inappropriately,” Dr. Atwood explains, “leading to cell dysfunction and death. This increased cell death leads to tissue dysfunction and disease, thereby killing less fertile older animals or people, preventing them from competing for resources with younger, more fertile individuals.”
Dr. Atwood thinks this theory better explains why stresses like extreme calorie restriction, exposure to cold, and “excessive” exercise appear to be associated with longer life, since calorie restriction has been shown to reduce reproductive hormones in female mammals. It may be the body interprets these stresses to mean that it’s not a good time to reproduce, and so decreases the amount of sex hormones it manufactures.
Maybe hormones hold the key to real anti-aging, rather than just changing appearances. But what about reports that hormone treatments may not prevent disease and dementia in women? In the U.S., the Women’s Health Initiative (WHI) hormone therapy trials were discontinued in 2002 because researchers found somewhat higher rates of some diseases in the group taking hormones. This same study also found that the estrogen plus progestin combination used in the trials didn’t prevent cognitive decline and actually seemed to increase dementia in some women over 65.
I asked Dr. Atwood if the results of the Women’s Health Initiative trials mean I shouldn’t consider taking hormones to decrease my risk of dementia. He said he feels that it’s very misleading to extrapolate the results of this study, in which Prempro and Premarin were used, to all forms of hormone replacement therapy. Prempro is a combination of conjugated equine estrogens and progestin in the form of the synthetic medroxyprogesterone acetate, and Premarin is made up of conjugated equine estrogens.
“Current hormone replacement therapies do not come close enough to replicating normal reproductive hormone levels,” he says, “since conjugated equine estrogens and medroxyprogesterone are not the major forms of sex steroids in the human body.” He points out that the WHI study contradicts results from numerous other animal and human studies showing that natural or bioidentical forms of these hormones protect neurons and may prevent dementia.
Hormones affect men too. A new study by researchers at the University of Washington Veterans Administration Puget Sound Health Care System found that low testosterone levels in men are associated with increased mortality rates. Looking specifically at dementia, the picture seems less clear. Scientists at the University Medical Center Utrecht in the Netherlands studied the link between reproductive hormones and Alzheimer’s disease (AD) in 2,974 men, aged 71 to 93 years for six years. They concluded “testosterone levels are not associated with risk for cognitive decline and AD, whereas higher estrogen levels increase risk for cognitive decline and AD”. In a small study at the University of California Los Angeles, testosterone supplementation in 16 men with Alzheimer’s improved their quality of life as reported by caregivers, but not their cognition.
It doesn’t seem to me there’s been enough research yet to know how various hormone replacement therapies will affect aging in general, let alone the risk of developing dementia. Dr. Atwood agrees that further research is needed. He and his colleagues are studying the neuroprotective effects of different formulations and delivery methods of female sex hormones.
He reminded me that research on aging and dementia has to have a broader focus than simply looking at estrogen and testosterone levels. “There are many other hormones that become dysregulated in the body following menopause and andropause,” he says, “and these have not been studied in any detail. Therefore, the dysregulation of estrogens and testosterone may be only part of the story.”
In the meantime, at least in theory, Gail and her mother could try to fool their bodies into keeping levels of luteinizing hormone and follicle stimulating hormone low by subjecting themselves to some of the stresses listed above. It’s hard to say whether this would slow their rate of progress to higher versions. For his part, Dr. Atwood doesn’t view calorie restriction as very attractive. “Rigorous exercise is the most practical anti-aging strategy until therapies that modulate reproductive hormones are developed,” he says.
I don’t think Gail will starve her mother, or sign her up for an Ironman race and the Polar Bear Club, but I guess this is the place to say that information in this post is not a substitute for medical advice. These measures could have life-threatening ill effects, particularly in older people.
With software, higher version numbers indicate greater stability and added functionality. Could this be true for life? Although I don’t want to develop dementia or another serious disease, I don’t really want to go back to Hormones 2.9 or even 3.9 either. So for now, I’ll watch for more research on the role of reproductive hormones in Alzheimer’s and aging, and head to the gym as often as I can. But I’m rebelling against the idea of looking “10 Years Younger”, and am growing my gray hair out. At least people will understand why I can’t find my car.
Whoa, whoa, whoa! Excellent post! I'm sooo impressed with the way you have handled the confusion and and lack of information surrounding aging (conditions that can only get better, since we are, as a species, now focusing on aging through a variety of discliplines and perspectives). I love your easy flex between the personal and "professional". Further, I love the comparison to versions of software. Reminds me a bit of Kurzweil, who expects that, sometime in the future, we will remake ourselves into creatures relatively like those featured in the movie "AI". Not that I relish this possibility, but, you know, if the Antareans visit again and Mom and I take off with them, I'd love to come back here in a century or so and see what humans have done with this idea, or whether it's been scrapped.
And, you're right, I won't be starving my mother, although I OFTEN kid her about initiating marathon training. I do notice, though, which I always thought was one of those self-evident things that happens for everyone, regardless of age, that when she moves physically a little more than usual (which, often, is almost no movement at all), she grooves mentally; so maybe training for the Ironman isn't what's necessary, when working with someone whose activity level has been self-restricted (as with my mother) for so long. Maybe, just pushing, a little at a time, beyond previous levels, may have a much more salutary effect than we currently imagine.
Anyway, lots to think about, here, very clear directions. Clarity like this, in the midst of the mud bath of "What is Aging?" in which we're currently indulging is exactly what is needed!
Bravo, Mona!
Posted by: Gail Rae Hudson | September 17, 2006 at 02:48 PM