Surprisingly Few Processes Can Be Thrown Into Reverse

The following is something of a cliche: scientists investigating genetics or biochemistry find a way to shorten life span in laboratory animals. They end their publication with the declared hope that further investigation will find a different manipulation of the same process that will extend life span. Here is an example of the type:

Scientists first noticed connection between aging and circadian rhythms in mice bred to lack a gene known as BMAL1.


Marina Antoch, a molecular biologist at the Lerner Research Institute in Cleveland, Ohio, and her team observed a group of 30 BMAL1 knockout mice. The knockout mice lived only half as long as 30 normal mice did, the researchers found. They also found that the knockout mice aged at an accelerated rate: By 18 weeks of age, the knockouts had lost a significant amount of fat, muscle, and bone mass. They also exhibited organ shrinkage in their spleens, kidneys, hearts, lungs, and testes--all signs of aging. And, like older humans, the BMAL1 mice lost hair and developed cataracts in one or both eyes.

Further experiments showed that mice lacking BMAL1 had anywhere from 10 to 50 percent higher tissue concentrations of harmful reactive species of oxygen and nitrogen, which are associated with the aging process. This finding suggests BMAL1 may help stave off aging by preventing the build-up of these species, says co-author Roman Kondratov, a molecular biologist also at the Lerner Research Institute.

"I think the next step is really tying this observation to the clock function of BMAL1," says cardiologist Garret FitzGerald of the University of Pennsylvania School of Medicine in Pittsburgh. If there is a functional link, he says, we may someday be able to manipulate our circadian clocks to prevent the ill effects of old age.

Whenever you see an article like this, mentally replace the biochemical process at hand with "blunt trauma" or "acid ingestion." You can certainly shorten life spans that way, but you are unlikely to find a way to extend longevity through the use of hammers and sulphuric acid.

You should also bear in mind that the appearance of accelerated aging is by no means an indicator that accelerated aging is in fact taking place. It was something of a big deal that certain human accelerated aging conditions were shown to actually be accelerated aging, for example. As another example, diabetes looks a lot like faster aging in many respects, but it isn't.

Surprisingly few biochemical processes are open to this sort of "let's find out how to throw it into reverse" logic, but the funding game requires one to pitch the next proposal ahead of time and on the basis of your latest research. Playing on past odds, I'd wager no significant healthy life extension will result from this research. The real payoff for this research will be a greater understanding of genetics, metabolism and cellular biochemistry - a noble goal in and of itself, but not a pitch that is likely to win friends and influence funding, sad to say. There is no useless knowledge in this space, for all that some paths forward seem more likely to pay off in longevity than others.

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