The Relevance of Naked Mole Rats

To what degree does it help to understand the mechanisms by which various species of long-lived mammals are in fact long-lived? That is an open question. There is a great deal of ongoing study of some of these species, such as naked mole rats, and efforts to at least sequence the DNA of others, such as some whales and longer-lived bats.

If we look to the more distant future, it seems fairly straightforward to argue that at the point at which it becomes possible to design new functional human genomes to support people with different metabolisms that nonetheless operate safely over the course of an extended lifetime, then yes, there might be a lot of beneficial alternative or additional modes of operation that can be pulled from the metabolic biochemistry of other species. Perhaps a significant fraction of the more beneficial aspects presently known to exist in other mammals can be made to work quite well in future variants of Homo sapiens machinatum. That isn't an unreasonable projection: it is all just a matter of knowledge and technology, and most of the fundamental technology needed to actually create alternative human genomes already exists or is near realization.

The research community is far behind on the knowledge front, however, and is thus a long, long way from being able to create any sort of stable alternative working metabolism in humans, let alone doing so safely. At the present time just trying to recreate the well-studied and easily achieved alternative metabolic mode of operation produced through the practice of calorie restriction is proving to be a challenge, with all too little to show other than an increase in knowledge after ten years and a few billion dollars - and this is really the first baby step on the road towards engineering entirely new human metabolisms that introduce other improvements.

So how much success should we expect from mining other species for their unusual and beneficial metabolic quirks in the near term? Researchers will certainly make good progress in understanding why naked mole rats are long-lived and immune to cancer in the next few years. There is momentum there. But that doesn't necessarily mean that scientists can then do anything with that knowledge immediately: knowing the signaling pathways or precise differences between rats and naked mole rats doesn't automatically result in ways to alter rats that will work. The operation of metabolism is fantastically complex, a linked web of protein machines all reacting to one another's presence. You can't alter anything in isolation, and it is always an expensive challenge to even prove safety for the comparative crude manipulations achieved today. So as I said above, it is an open question as to whether the outcome of the study of long-lived mammals is simply more knowledge or something more useful than that.

Here is a good popular science article that gives an overview of work on naked mole rat metabolism, details of some of the latest results, and the hopes of the researchers involved:

The end of aging: do naked mole rats have the secret to long, healthy lives?

When he first saw a naked mole rat in 1842, German naturalist and explorer Eduard Rüppell thought he might have found a diseased specimen because it lacked fur. But there's something special about naked mole rats that Rüppell couldn't have seen. Similarly-sized rodents, under ideal conditions, can live for five years or less. The life span of a naked mole rat is about six times as long. Even into their twenties, they barely seem to age, retaining strong heartbeats, dense bones, and remaining fertile. Scientists have dosed them with all sorts of carcinogenic chemicals and radiation, but unlike every other mammal, a naked mole rat has never once been observed to develop cancer.

Until recently, what let the naked mole rats conquer cancer and live so long was a total mystery. But over the past few years, a handful of researchers around the world have uncovered strange mechanisms inside their cells that seem to be the basis for the animals' uncommon longevity. The scientists' ambition is lofty, but not surprising: they want to harness these discoveries to one day vanquish cancer and battle aging in humans too.

Upon hearing about these discoveries, most people ask the same reasonable question: can they be applied to cure cancer and slow aging in humans? The answer, like many in science, is complicated. It's one thing to discover a rodent has marvelous adaptations that allow it to live a really long time. It's another entirely to put them in another species.

Where where I stand, work on understanding longevity in other species looks like just another path to slowing aging through altering metabolism. It is fascinating, but highly unlikely to produce therapies that will greatly extend life or restore health to the old. Slowing aging just slows down the accumulation of damage, which is of limited benefit to those already very damaged by aging. The only types of treatment that will be of great benefit to the elderly are those based on repair of the causes of aging, restoring the metabolism we already have rather than building a new one, as these are in theory capable of actual rejuvenation when realized. Since we might expect at least another two decades to pass before any useful and widespread medical technologies emerge from any lines of present research into treating aging, then we should firmly reject the goal of slowing aging in favor of the goal of repairing and reversing aging. Why work so hard on a course of action that will produce end results that are of no benefit to your older self?


I think looking at the anti-cancer mechanism might be of some benefit even if only to rule it out as a possible therapy.

Posted by: Michael at June 17th, 2014 5:00 AM

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.