Programming Genes to Extend Life SpanSeptember 2011
By Charles Platt
Skeptics who question whether aging can be conquered often make the problem appear more complicated than it may be.
Differences in gene expression between young people and older people are a well-documented fact.1,2 In simple terms, almost all the processes in our bodies work better when we are young. Many of us make it to age 50 or beyond before changes in gene expression manifest themselves as serious illnesses.
In the future, we will be able to control (i.e., reprogram) our genes as readily as we do our computers. Some scientists believe that as a result of this, humans may theoretically remain young and healthy for very much longer than they do today.
Restoration of youthful gene expression would enable cells, tissues, and organs to grow younger as opposed to the degenerative downward spiral that now occurs.
We already exert some control over our gene expression with the lifestyle we choose and the supplements we ingest such as fish oil, vitamin D, pterostilbene, and resveratrol.
Scientists have only recently come to the realization that foods, nutrients, and medications that make us healthier do so in part because they induce the expression of health-promoting genes and reduce the expression of disease-promoting genes. Consumption of toxic foods and chemicals, on the other hand, induces the expression of disease-promoting genes and reduces the expression of health-promoting genes.3-5
Those who argue about cumulative damage to the body forget how healthy most children are, how they get healthier as they mature into young adulthood, and only then begin to decline. Youthful gene expression enables most children to maintain a relatively good state of health—until the bad genes overexpress while beneficial ones underexpress—and pathologic aging ensues.
This article focuses on the possibility of altering gene expression for the purposes of extending healthy life span. This science is in its infancy, but it is clearly leading to the time when scientists will develop genetic engineering and stem cell therapies that will enable physicians to reverse aging and help us to grow younger and healthier with advancing age.
Rewriting the Aging Program
We live in an exciting time. Many scientists now agree that there are genetic mechanisms that control the aging process, and the implication of this is that it will eventually become possible to reverse aging and cure the diseases of aging.
We still have no comprehensive model explaining how aging occurs, but we know a great deal about how aging manifests itself, and we are beginning to learn how to reverse it.
This becomes evident to anyone who reads The Future of Aging, a massive scholarly volume that includes articles by some of the most prominent researchers in the field.6 In June of this year I spoke to Dr. Gregory Fahy, the editor-in-chief of the book, while he was attending the annual American Aging Association meeting. “One of the purposes of this book was to present the case for genetic causes of aging in a way that my colleagues will find difficult to ignore,” Dr. Fahy told me.
“Aging is not just due to local wear and tear,” Fahy concludes. “For example, in flies and worms, it has been shown to be a process controlled in significant part by the brain.”6
Dr. Fahy’s outlook is strongly supported by much work on C. elegans, a small nematode (worm) that is widely used by biologists because it is so easily studied. At the same time, like all living things, it has its own DNA, bearing some resemblance to our own. It also has organs, intestines, and ganglia (nerve cell clumps that operate in some cases like our brains), eats food and reproduces, making it an ideal model for testing genetic modifications. Fahy reports that in recent work, the Shmookler-Reis lab succeeded in creating a genetic variant of C. elegans that has ten times the normal life span of the standard organism.6 Cynthia Kenyon and her coworkers had previously reported a six-fold life span increase in Science magazine.7 These astonishing changes in longevity were entirely caused by reducing the expression of a few master genes.
Similarly, gene expression changes are the major explanation for the results reported by Dr. Michael Rose, who claims to have quadrupled the average life span of fruit flies merely by selective breeding.8 “The idea that aging is just a cumulative process of damage is fundamentally incorrect,” Rose commented when I spoke to him about his work. As a coauthor of the new book Does Aging Stop? from Oxford University Press, Rose points out that some organisms already cease to age late in life. “We have fly populations where 40% of the cohort stops aging,” he says.
Why, then, do some scientists—even within the aging field—remain skeptical?
Dr. Rose suggests that processes in biology are making a transition from being described entirely by words to being defined by mathematics. “The less mathematical scientists are, the longer it takes for them to change their minds,” he says. “Words give you much more opportunity for self-deception. Mathematics allows predictions that can be verified. Galileo was influential because he replaced words with equations.”
Gregory Fahy sees biological conservatism as being simply a facet of human nature. “Most scientists tend to be scientifically conservative,” he says. “They’re thinking about their next experiment and not necessarily about the broader relationships between genes and aging. And most biologists are discovery-oriented, not intervention-oriented.”
Even biogerontologists may underestimate the meaning of the breakthrough work by scientists such as Robert Shmookler-Reis, Cynthia Kenyon, and Michael Rose. The traditional outlook is that genes only control a relatively small proportion of the aging process, often estimated at around 30%.9,10 After all, studies of identical twins have shown that genes only explain some of their differences in aging. “But of course, environmental influences such as diet and exercise can strongly influence gene expression!” Fahy comments. “My hypothesis is that if you can trace an aging process back far enough, there’s almost always a gene at the root of what you find.”