Cancer and Telomerase:
What Roles Mice Play
Mice and Their Phenomenally Long Telomeres
Laboratory mice have telomeres that are 10 times as long as human telomeres, and in addition, somatic tissue in laboratory mice produces telomerase. Under these circumstances, mice can't very well senesce if senescence is the consequence of a shortening of their telomeres. The authors quote an observation made by P. Alexander in 1966 ("Is there a relationship between aging, the shortening of life-span by radiation and the induction of somatic mutations?" In: Shock, N. W., Thomas, C. C., Perspectives in Experimental Gerontology, pp. 266-279) in which he wrote:
."The most striking fact is that even very old [lab] mice (e. g., more than 2.5 years old) when killed while still fit have remarkably few pathologies and are almost indistinguishable from young animals."
The first question that comes to mind is: How long can these mice live if experimentalists don't kill them? And if they die in excellent condition, what kills them? My recollection of the mortality curves for mice is that they die off in accordance with a Gompertz curve, and that they often die of renal failure. But why should their kidneys fail if they don't age?
This situation also suggests that long telomeres don't greatly influence the rate of aging.
I also recall reading how old old lab rodents look, which doesn't tally with P. Alexander's characterization of aged mice(?).
Why Don't Long Telomeres Mean Early Cancer for Lab Mice?
Since murine cells have enormous potential for proliferation (200 divisions? 500 divisions?), why don't they die young of cancer? It doesn't take a very large tumor to stop a mouse. A 2-centimeter tumor in a human (31 cell divisions) would correspond to a 1-millimeter tumor in a mouse (20 cell divisions).
The authors suggest that living in the protected world of the lab (except for those human experimenters), lab mice have been shielded from environmental insults, such as mutagens, pathogens, and improper nutrition. Also, mice have 1/500th as many cells as humans, and these are the reason that, even though lab mice have long, long telomeres, they don't contract cancers at an early age. The authors speculate that larger animals would develop too many youthful tumors to be viable through the reproductive phase..
Do Wild Mice Have Short Telomeres?
One of the authors (BSW) predicted that wild mice would have much shorter telomeres than lab mice. An experimental analysis of recently tamed wild mice showed telomeres only about one-tenth the lengths of the telomeres of the long-domesticated lab mice. The authors speculate that wild mice will senesce earlier than lab mice (although most wild mice won't live long enough to grow old), but that, on the other hand, wild mice will be much more resistant to cancer arising from harmful environmental influences in their unprotected habitats.
The authors suggest that these long telomeres arise in lab mice because they're chosen for early breeding prolificity, and that longer telomeres are positively correlated with higher breeding profligacy. Over the past few decades, this artificial selection imposed by human breeders has had the unintended side effect of greatly extending the telomeres of captive mice. The small-animal cell count of the lab mice, plus the sheltered environment of the lab (protecting these mice from early cancer) has enabled this rapid (50-generation? 100-generation?) evolution of lab mice.
In other words, we've unwittingly modified nature's design..
Lab Mice May Not Be the Good Models for Drug-Testing We've Supposed
The authors suggest that because lab mice have such long telomeres, they may not make such good models for testing drugs intended for humans. They may under-react to toxins that could accelerate aging in humans or could show their harmful effects in old age, and lab mice may overreact to carcinogens and cancer promoters because of their long telomeres and presumed vulnerability to carcinogens.
Do you suppose there would be a furor if these authors turn out to be correct, and our drug testing over the past 50 or 60 years has been invalid because we've been using modified mice?