By Dov Michaeli
“Methus’lah lived nine hundred years;
Methus’lah lived nine hundred years;
But who calls dat livin’ when no gal’ll give in
To no man what’s nine hundred years.”
“It ain’t necessarily so”, Porgy and Bess by George Gershwin
Isn’t that the ideal most people strive for? Never mind living to 120; what we want is to live healthy to whatever age biology allotted us. Age is the major risk factor for most cancers and for chronic diseases like arthritis. Why is it? Evolutionary biologists tell us that this is nature’s way of clearing us off the stage, so as not to compete with the young for resources. Maybe. I find this theory a bit unsatisfying, if for no other reason than the fact that lower species, like bacteria and fungi, basically live almost forever (they do eventually do die out by senescence) because every mother cell simply divides into two brand new daughter cells. Other species, invertebrates as well as some vertebrates, use the process of parthenogenesis, or asexual reproduction involving the egg only without fertilization by the sperm (no fun there, except for some man-haters who love the concept), thus forming genetic clones of the mother. Also, most organisms in nature rarely live to their biologically-determined limit –they fall prey to disease and predators. So aging per se couldn’t be a major selective force.
Be it as it may, it is an undisputed fact that every tissue and organ in our body undergoes gradual decline with aging.
A New Approach in the study of Aging
Rather than passively accept our biological fate of inexorable decline, wouldn’t it be nice to clear the stage while we are fit and hale? A truly surprising breakthrough toward this goal was achieved recently by Drs. Darren J. baker and Jan M. van Deursen, and their colleagues at the Mayo clinic in Syracuse, Minnesota (Nature, online 2 november, 2011). It has been known that senescent, or aging, cells disintegrate and in doing so release inflammatory proteins that cause damage to the surrounding tissue. Hence we lose not only the dying cells, but they take down with them perfectly healthy cells. That is a major reason why we get wrinkles and lose muscle mass as we get older. So it makes sense to see what would happen if we could somehow purge those dying cells before they inflict their damage. But how do you target specifically the senescent cells and spare the healthy ones?
The investigators took advantage of the observation that a certain gene, P16INK4A , gets activated when cells undergo senescence. P16INK4A is part of the control mechanism that brings cell division to a halt when their time has come. So here is the ingenious device: they linked a gene that makes a protein that can kill the cell, to the genetic switch that turns on P16INK4A . But that protein becomes active only when a certain drug is added. So here we have the equivalent of a land-mine: the cell reaches its limit of division and switches on P16INK4A , which in turn switches on the “bomb” gene, which produces the protein that will “blow up” the cell (actually, dissolve it) when the drug is added.
The animals they selected for this experiment were mice that mimicked the human disease of progeria, where the afflicted individuals go through all the stages of aging within 10-15 years of life, and usually die of heart disease. The picture below is of a 12 year old child with progeria.
The results were astounding. Mice given the drug every three days from birth suffered far less age-related body-wasting than those which were not. They lost less fatty tissue. Their muscles retained their volume and strength, and they had no cataracts of the eye. They did, though, continue to experience age-related problems in tissues that do not produce P16INK4A as they get old. In particular, their hearts and blood vessels aged at the same rate as untreated mice. For that reason, since heart failure is the main cause of death in such mice, their lifespan was not extended.
In another experiment they started administering the drug in mid-life rather than from birth. The results were equally impressive: they stopped the aging process in the fat, muscle and eye tissues. They even reversed some of the fat and muscle losses.
The picture below shows two 9-month-old mice from the study. The one on the right received the drug to eliminate senescent cells (from the NYT, 2 November, 2011, taken by Jan van Deursen).
The Implications are Profound
This paper, if confirmed by normal mice rather than the progeric (rapidly aging) ones, is a game changer. Until now, research on aging focused on life extension. This approach focuses of healthy aging. Given our progressively longer life, our health care system is already groaning under the weight of rapid increases in chronic diseases in the elderly. If this trend continues we will devote 40% of our GDP to health care. The social and economic implications are dire: fewer and fewer young people will support more and more sickly elderly retirees. Inter-generational tensions are already beginning to surface.
This research holds the promise of turning this dismal outlook on its head. Rather than adding millions of sickly elderlies to rolls of Medicare ,we could have millions of new healthy adults, continuing to work and contributing, rather than burdening, our society. Truly revolutionary.