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Chromosomes, artwork
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Switched on Chromosomes

Source: © Sciepro/Science Photo Library/Corbis

Resisting Destiny

Ill-Fitting Genes

Why you should care

Wouldn’t you rather sport a genetic destiny that fits your personal style — rather than be forced to wear Grandma’s dementia, Dad’s heart attack or cousin Sue’s diabetes?

If you thought Angelina Jolie’s decision to undergo a bilateral mastectomy was extreme, you’d be right. But it was justifiably and courageously so: Desperate circumstances call for extreme measures. But do your genes inexorably write your destiny with respect to your fitness and health? The answer may surprise you.

Every one of the 25,000 genes you inherit from Mom and Dad is something like a lightbulb that can’t be changed — but can be adjusted with a dimmer switch.

Few of us, happily, are faced with wrenching decisions like Ms. Jolie’s because genetic variations that predestine us to grim outcomes are rare. Most of us have dodged the inheritance of genes as wicked as her BRAC1 variant and instead are born with garden-variety genes with less deterministic authority. And, as new research increasingly demonstrates, you have the power to influence many of them to improve your health, without gene therapy or radical surgery.

That’s because every one of the 25,000 genes you inherit from Mom and Dad are like a lightbulb that can’t be changed — but can be adjusted with a dimmer switch. That’s really how genes work. Every gene within each of the trillions of cells in your body is under constant regulation to be ON, OFF or somewhere in between. Scientists like me and my colleagues at the Gladstone Institutes in San Francisco — a think tank and innovation lab working to solve big problems in medicine — call this epigenetics or gene regulation, which can determine your state of health as much as or more than the DNA sequences of your genes themselves.

Did you know that a heart cell actually contains exactly the same genes as a brain cell? It’s just that as embryos, our “BE A HEART CELL” genes are switched on or activated — while our “BE A BRAIN CELL” genes are turned off or repressed in the heart. As embryos we don’t have voluntary control over these epigenetic events, but as adults we gain a measure of self-determination over many of our genes.

For example, you have sets of “RESIST FATIGUE” genes and “RESIST DIABETES” genes that convey important instructions to your cells. Scientists such as Ron Evans, Eric Verdin, Bruce Spiegelman and Eric Olson have discovered molecular details of how the switches on these genes function, and I’ve contributed to this area myself.

Research by Evans illuminated gene switches that regulate body fat and keep animals lean and free of diabetes, even when overeating. Spiegelman discovered the master regulator of mitochondria, the energy factories of our cells. Verdin found gene switches that slow the aging process, and Olsen discovered how to control the size and health of the heart. Several of these labs, including my own, demonstrated how these switches work by genetic engineering of mice to have the fitness and healthy physiology of marathon runners without having to train.

By powering through your daily exercise routine, you can turn up the lights on these sets of genes, thereby instructing your cells to make changes…

Here’s where you come in. The gene switches discovered by these scientists are under your personal control. By powering through your daily exercise routine, you can turn up the lights on these sets of genes, thereby instructing your cells to make the changes necessary for achieving a new personal best at Sunday’s 10K race — rather than collapsing in the first mile. And with each step, you also build your resistance to diabetes.

Interesting, you may say, but old hat — we all know that exercise is good for us. What’s really new, however, is that soon we’ll be able to measure the biological effects of exercise within our bodies, and not simply how much and what type of exercise we’ve performed. When it comes to health-promoting consequences of exercise (or diet), one size does not fit all. Each person’s genes respond to exercise differently. What you really want to know, and look to biotechnologists to provide biosensors to accomplish, is whether the exercise you’re doing is having the desired effects on the “RESIST DIABETES” genes and others of that nature.

Still, we all know that even the best lifestyle choices can’t fix everything. What about those merciless gene variants that can’t be modulated by healthy habits?

Presentation at Circle of Care - Recent Developments in Alzheimer's Research - Yaisa Andrews Zwilling, PHD

Source: YouTube

Presentation at Circle of Care - Recent Developments in Alzheimer’s Research - Yaisa Andrews Zwilling, PHD

Such circumstances require a high-tech fix, and scientists are discovering more each day about how to control all-important genes in order to overcome disease. My friend Shinya Yamanaka won the Nobel Prize in 2012 for showing the world how to control the gene switches that create the unique capabilities of embryonic stem cells. His work has triggered a revolution in cellular reprogramming that seems likely to enable cures for diabetes, heart disease and blindness.

Other scientists like Yaisa Andrews-Zwilling (pictured) are exploring ways to neutralize the effects of a nasty gene variant called ApoE4 that raises the risk for traumatic brain injury and Alzheimer’s disease.

In the not-so-distant future, there will come a day when you’ll tune your diet and workouts based on biosensor readings that read out the positions of dimmer switches on your genes. And if you happen to find yourself with some ill-fitting genes, biotechnologists will be able to re-tailor those parts of your genetic code not amenable to simple measures — thus ensuring that you won’t be compelled to wear Grandma’s dementia, Dad’s heart attack or cousin’s Sue’s diabetes.

R. Sanders (Sandy) Williams is president of the Gladstone Institutes and a professor of medicine at the University of California San Francisco. Formerly dean of Duke University’s medical school, he has served on various boards and professional associations, including the board of reviewing editors of Science magazine.

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