A Blog Around The Clock

Sometimes a metaphor used in science is useful for research but not so useful when it comes to popular perceptions. And sometimes even scientists come under the spell of the metaphor. One of those unfortunate two-faced metaphors is the metaphor of the Biological Clock.

First of all, there are at least three common meanings of the term - it is used to describe circadian rhythms, to describe the rate of sequence change in the DNA over geological time, and to describe the reaching of a certain age at which human fertility drops off ("my clock is ticking").

I prefer the Rube-Goldberg Machine metaphor for the mechanism underlying circadian rhythms, but apparently more people know what a clock is than what a Rube-Goldberg Machine is so it appears that we are stuck with the Clock Metaphor for a while.

Once you have a clock metaphor, it is easy to see a clock everywhere you look. Like seeing nails with a hammer in your hand, a researcher in choronobiology is likely to see timing everywhere - I know, I do it myself.

And sometimes this approach pays off - there is definitely a link between circadian and developmental timing in Nematodes, between circadian timing and timing of the love-song in Drosophila, between circadian and seasonal timing, to name some of the few well-known connections, each discovered by a circadian biologist intirgued by the possibility that a clock at one domain (days) may also be involved in timing at other domains (miliseconds, hours, weeks or years).

One of the most touted, yet the most tenuos connection is that between circadian timing and timing of aging and death. Much funding has already been poured into studying this, but, apart from figuring out how circadian rhythms themselves change with age (yup, like everything else, the clock gets a little sloppy and the rhythms get fragmented so you tend to nap more often), no such link has been found yet.

But funding needs to be renewed, and it is just so easy to mix metaphors here - "my clock is ticking" and "my circadian clock is ticking" are so easy to sell together as a package.

Thus, I was not too impressed when I saw this press release: Link Between The Circadian Clock And Aging:

Studying a strain of transgenic mice lacking the core circadian clock gene, Bmal1, Dr. Antoch and colleagues determined that BMAL1 also plays an important role in aging. Bmal1-deficient mice display a marked premature aging phenotype: By 4-7 months of age, the Bmal1 knockout mice experience weight loss, organ shrinkage, skin and hair weakening, cataracts, cornea inflammation and premature death.

The researchers went on to show that BMAL1's influence on the aging process is due to its previously established role in protecting the organism from the genotoxic stress. Some BMAL1-deficient tissues - like the kidney, heart and spleen - accumulate aberrantly high levels of free radicals. The scientists believe that oxidative stress may underlie premature aging in these animals.

Future research will be aimed at delineating BMAL1 target genes involved in the aging process, with the ultimate goal of elucidating molecular targets for the rational design of drugs aimed at alleviating specific, age-related pathologies. "The involvement of BMAL1, the key component of the molecular clock, in control of aging, provides a novel link between the circadian system, environment and disease and makes circadian proteins potential drug targets," explains Dr. Antoch.

If you knock out a gene or two, you get messed-up animals. Genes do not work in isolation - they are parts of multiple networks. Knocking one out will mess up multiplenetworks of genes, thus multiple processed in cells. Cells will then compensate fine-tuning other processes, etc. In short = knockout animals are sick animals.

I was going to completely ignore this, but then I saw this nice put down: Surprisingly Few Processes Can Be Thrown Into Reverse:

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.

Exactly. Read the whole thing and do not buy stock in synthetic BMAL just yet....