Fight Aging!

So the future of medicine is golden, biotechnology is in the throes of a vast expansion of capabilities and free-fall in costs, and we have a good idea as to how to go about reversing aging - if the research community would just stop tinkering with efforts to merely slow down aging and get on with achieving the all-round better goal of rejuvenation. We should all donate money and time to help out, because it's not as though we can take it with us and irreplaceable time is ticking away. A shot at lifespans of centuries and longer is coming, with not so much time left in which to reach for that goal.

Putting all of that to one side for the moment, there is the arguably less important question of how to optimize heath and life span given the present poor tools to hand. Many people spend a great deal of time talking and debating on this topic, immersing themselves in the world of what presently exists, and giving little thought to what might lie ahead. A vast industry caters to people who think they've found the better mousetrap when it comes to personal health and aging. They're all wrong, of course, but that doesn't stop the flow of commerce.

The sad truth of the matter is that it's simple and easy to achieve the 80/20 result in health and longevity within the bounds of the tools we have available to us today, provided you're starting out as a basically ordinary, healthy individual. Exercise regularly, the 30 minutes daily of aerobic exercise that has been recommended by physicians since way back when, and practice calorie restriction with optimal nutrition - i.e. eat a sane diet, not very much of it, and obtain the necessary levels of micronutrients while doing so. There's also the matter of not harming yourself greatly, but just as I shouldn't have to mention avoidance of knives and falling rocks, I shouldn't have to mention things like giving up smoking.

These things are not rocket science. They are widely known and most have been advocated for centuries. The supporting statistical data is far better now than at any point in the past, and so you have no excuses: if you're not adopting these practices then it is because you have decided to accept a shorter life expectancy and greater odds of ill health in exchange for the dissipations that you presently enjoy. No-one's perfect, right?

But here is an interesting thing about trying to reliably forge ahead beyond the 80/20 point in personal health, in search of the optimum level of improvement: it's next to impossible to go further or reliably measure that you have gone further. The research community has expended billions without being able to determine how you can do that - so what makes you think that you can do any better given your far more limited resources? Metabolism and its interactions are so very, very complex. We can list with some confidence what is good for you, but talking about what is optimal is far beyond present capabilities.

For example, to pick one line item, let us consider calorie restriction. It works amazingly well in short-lived animals and improves short-term measures of human health far more than any presently available medical technology can manage. But once we get to an examination of longer lived animals (such as we primates) over the long term, it starts to become much harder to pin down the best, most optimal way to do things - certainly, the present primate studies are beginning to look as though they will generate as much ambiguity as data.

Dietary Restriction: critical cofactors to separate healthspan from lifespan benefits

Dietary restriction (DR), typically a 20-40% reduction in ad libitum or "normal" nutritional energy intake, has been reported to extend lifespan in diverse organisms including yeast, nematodes, spiders, fruit flies, mice, rats and rhesus monkeys. The magnitude of the lifespan enhancement appears to diminish with increasing organismal complexity. However, the extent of lifespan extension has been notoriously inconsistent, especially in mammals.

Recently, Mattison et al. report that DR does not extend lifespan in rhesus monkeys in contrast to earlier work of Colman et al. Examination of these papers identifies multiple potential confounding factors. Among these are the varied genetic backgrounds and composition of the "normal" and DR diets. In the monkeys, the correlation of DR with increased healthspan is stronger than that seen with lifespan, and indeed may be separable. Recent mechanistic studies in Drosophila implicate non-genetic cofactors such as level of physical activity and muscular fatty acid metabolism in the benefits of DR. These results should be followed up in mammals. Perhaps levels of physical activity among the cohorts of rhesus monkeys contributes to inconsistent DR effects.

To understand the maximum potential benefits from DR requires differentiating fundamental effects on aging at the cellular and molecular levels from suppression of age-associated diseases, such as cancer. To that end, it is important that investigators carefully evaluate the effects of DR on biomarkers of molecular aging, such as mutation rate and epigenomic alterations. Several short-term studies show that humans may benefit from DR in as little as 6 months, by achieving lowered fasting insulin levels and improved cardiovascular health.

Optimized healthspan engineering will require a much deeper understanding of DR.

That last sentence is worth considering at length - but remember that the 80/20 win for personal health is still right here, easily achieved. Instead of trying to go further in a presently impossible attempt at optimization, a better use of that time and energy lies in supporting research and development of rejuvenation biotechnology. Even a magically optimized personal health program would not allow most people to live to 100 with today's technology - the only way that the vast majority of us will get to see a three digit birthday cake is through progress in longevity science and its clinical applications.

So if you're going to spend any effort on this whole living longer in good health thing, spend it wisely. Don't chase rainbows.