Fight Aging!

Prior to the discovery of single genes that could be mutated, silenced, or otherwise altered to significantly extend longevity in lower animals, such a thing was thought very unlikely. Which is to say that nobody really thought about it at all - it wasn't a possibility within the paradigm of understanding for aging and metabolic processes. Now, of course, researchers have a variety of longevity mutations in hand in species ranging from worms to rodents, and more are being discovered with each passing year. Some technology demonstrations built atop these mutations have extended healthy life by as much as 50% in mammals (by combining a few methods), and far more than that in nematode worms.

But I'm not an advocate of chasing metabolic manipulation as a primary method of enhancing human longevity. This is primarily because it will produce therapies that only slow aging, and are thus far less effective than a repair strategy aimed at reversing aging. Slowing aging does little for those already old, and is a one-shot deal. Repair methodologies help the old and can be used over and again. Beyond that one can also reasonably argue that the repair strategies will be less costly to develop given the present state of scientific knowledge.

One has to regularly re-examine one's prejudices, however. The question for today is whether there exist as yet undiscovered and comparatively simple mutations in humans that will significantly extend healthy and maximum life spans. How likely is this, given what we know to date? Are potential human longevity mutations worth chasing?

The layperson only has a couple of data points to go on here:

• No human study can yet point to genetic differences that add up to more than a couple of years of life expectancy, and that's usually a matter of statistical analysis and/or resistance to one specific age-related disease.
• Single gene longevity mutations in other species were not thought plausible until discovered.
• Based on results obtained in calorie restriction studies, researchers don't expect metabolic changes to produce anywhere near as great an effect on longevity in humans as they do in mice.
• Much of the work on human longevity effects is inherently speculative; researchers are still striving to develop good tools that predict life expectancy or determine age in longer-lived animals.

We humans are already an unusually long-lived species if you compare us with other mammals of similar size. That seems to bring with it a diminished return on metabolic changes with significant effects in lower animals. It's an open question as to whether that applies to changes that go beyond what the body is capable of itself in response to diet, and beyond the minor variations in human genotypes.

Based on what I've seen over the past decade, I would not be surprised to see mouse life span doubled ten years from now through some ingenious combination of simple gene engineering and altered cellular processes - i.e. through slowing aging rather than repairing damage. Researchers are already half way there. Equally, I would not be surprised to see single human genes discovered that when manipulated or silenced can produce an expected change in life expectancy on a par with the expected changes for exercise and calorie restriction. This is to say something between a few years to an additional decade of healthy life, and an unknown effect on maximum life span. (Note that I say "expected" here. Even the figures for exercise based on demographic studies could be overturned with sufficient new data, and life expectancy predictions for human calorie restriction are just that - predictions).

I would be very surprised if anything greater than that jumps out of a single gene mutation in humans. But my expected level of surprise is not a rigorous assessment. The rigorous assessment would be "probability unknown." There were all sorts of plausible evolutionary arguments as to why researchers wouldn't discover any simple change in an animal's genes that greatly improved its longevity - all wrong, obviously. Similarly, all it takes is one discovery in humans to make the present wisdom gained from calorie restriction studies and further evolutionary arguments wrong as well. Our present longevity is very much determined by evolution - look at how widely life spans vary between similar species - but that doesn't mean we yet fully understand why and how.

So as research in lower mammals and other primates continues, scientists will increasingly build upon it to explore alterations in the human genome. But I don't see it as the best path forward to enhancing longevity for those of us reading this today. We will be decades older before any material benefit is realized - and that much less able to benefit from a technology that can only slow down aging. Our self interest is much more aligned with projects that could greatly improve health and longevity for the aged, and which could be realized in a similar time frame.