2009 : WHAT WILL CHANGE EVERYTHING?

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Emeritus Professor of Physics and Astronomy, UC-Irvine; Novelist, Shipstar
LIVE TO 150

I expect to see this happen, because I'll be living longer. Maybe even to 150, about 30 more years than any human is known to have lived.

I expect this because I've worked on it, seen the consequences of genomics when applied to the complex problem of our aging.

Since Aristotle, many scientists and even some physicians (who should know better) thought that aging arises from a few mechanisms that make our bodies deteriorate. Instead, the genomic revolution of the last decade now promises a true 21st Century path to extending longevity: follow the pathways.

Genomics now reveals what physicians intuited: the staggering complexity of aging pathophysiology among real clinical patients. We can't solve "the aging problem" using the standard research methods of cell biology, despite the great success such methods had with some other medical problems.

Aging is not a process of deterioration actively built by natural selection. Instead it arises from a lack of such natural selection in later adulthood. Not understanding this explains the age-old failures to explain or control aging and the chronic diseases underlying it.

Aging comes from multiple genetic deficiencies, not a single biochemical problem.

But now we have genomics to reveal all the genes in an organism. More, we can monitor how each and every one of them expresses in our bodies. Genomics, working with geriatric pathology, now unveils the intricate problems of coordination among aging organ systems. Population genetics illuminates aging's cause and so, soon enough, its control. Aging arises from interconnected complexity hundreds of times greater than cell biologists thought before the late 1990s.

The many-headed monster of aging can't be stopped by any vaccine or by supplying a single missing enzyme. There are no "master regulatory" genes, or avenues of accumulating damage. Instead, there any complex pathways that inevitably trade current performance for longterm decay. Eventually that evolutionary strategy catches up with us.

So the aging riddle is inherently genomic in scale. There is no biochemical or cellular necessity to aging—it arises from side effects of evolution, through natural selection. But this also means we can attack it by using directed evolution.

Michael Rose at UC Irvine has produced "Methuselah flies" that live over four times longer than control flies in the lab. He did this by not allowing their eggs to hatch, until half are dead, for hundreds of generations. Methuselah flies are more robust, not less, and so resist stress.

Methuselah flies genomics shows us densely overlapping pathways. Directed evolution uses these to enhance longevity. Since flies have about ¾ of their genes in common with us, this tells us much about our own pathways. We now know many of these pathways and can enhance their resistance to the many disorders of aging.

By finding substances that can enhance the action of those pathways, we have a 21st Century approach to aging. Such research is rapidly ongoing in private companies, including one I co-founded only three years ago. The field is moving fast. The genomic revolution makes the use of multi-pathway treatments to offset aging inevitable.

Knowledge comes first, then its use. Science yields engineering. Already there seems no fundamental reason why we cannot live to 150 years or longer. After all, nature has done quite well on her own. We know of a 4,800-year-old bristlecone pine, a 400 year old clam—plus whales, a tortoise and koi fish over 200 years old—all without technology. After all, these organisms use pathways we share, and can now understand.

It will take decades to find the many ways of acting on the longevity genes we already know. Nature spent several billion years developing these pathways; we must plumb them with smart modern tools. The technology emerging now acts on these basic pathways to immediately effect all types of organs. Traditionally, medicine focuses on disease by isolating and studying organs. Fair enough, for then. Now it is better to focus on entire organisms. Only genomics can do this. It looks at the entire picture.

Quite soon, simple pills containing designer supplements will target our most common disorders — cardiovascular, diabetes, neurological. Beyond that, the era of affordable, personal genomics makes possible designer supplements, now called neutrigenomics. Tailored to each personal genome, these can enforce the repair mechanisms and augmentations that nature herself provided to the genomically fortunate.

So…what if it works?

The prospect of steadily extending our lifespans terrifies some governments. These will yield, over time, to pressures to let us work longer—certainly far beyond the 65 years imposed by most European Union countries. Slowly it will dawn that vibrant old age is a boon, not a curse.

Living to 150 ensures that you take the long view. You're going to live in a future ecology, so better be sure it's livable. You'll need longterm investments, so think longterm. Social problems will belong to you, not some distant others, because problems evolve and you'll be around to see them.

Rather than isolating people, "old age" will lead to social growth. With robust health to go with longer lives, the older will become more socially responsible, bringing both experience and steady energy to bear.

We need fear no senioropolis of caution and withdrawal. Once society realizes that people who get educated in 20 years can use that education for another century or so, working well beyond 100, all the 20th Century social agenda vanishes. Nobody will retire at 65. People will switch careers, try out their dreams, perhaps find new mates and passions. We will see that experience can damp the ardent passions of glib youth, if it has a healthy body to work through. That future will be more mature, and richer for it.

All this social promise emerges from the genomic revolution. The 21st Century has scarcely begun, and already it looks as though most who welcomed it in will see it out–happily, after a good swim in the morning and a vigorous party that night, to welcome in the 22nd. The first person to live to 150 may be reading this right now.