Why growing older is the greatest carcinogen
The Life span of a living organism may have its own clock, a recent study suggests. Degenerative genetic changes manifest at a certain point in life, that is, at a certain time after birth these changes take place no matter how long the life span is. Therefore, growing older is the greatest risk of accumulating adverse genetic changes that can lead to the development of cancer and many other age-related diseases.
This means that living longer does not necessarily indicate that one has less genetic damage, but it could simply mean that one lived longer with more of this damage.
Scientists at Fred Hutchinson Cancer Research Center have made a landmark discovery in yeast that may hold the key to revealing that growing older is the greatest cancer-risk factors in humans. Their findings appear in the September 26 issue of Science.
Daniel Gottschling, a member of Fred Hutchinson s basic science division, and the first author Michael McMurray, a graduate student, have found striking similarities between humans and simple baker s yeast with regard to the changes their genes undergo as they age.
While yeast don’t get cancer, they do have one of the major hallmarks of malignancy, which is genetic instability, Gottschling said. We found a similar thing in yeast that has been seen in humans: genetic instability shoots up dramatically in the middle to late stages of life. When the yeast cells attain the equivalent of late to middle age, the researchers discovered they experience a sudden, 200-fold surge in the production of genetic changes typically manifested as a loss of heterozygosity (LOH), a condition characterized by missing or mutated chromosomes. These findings suggest that the yeast, a single-celled organism, may be an ideal model for understanding the complexities of age-related cancer development in humans.
To determine whether yeast could be used as a model to help explain the abrupt increase in human cancer risk, the researchers tracked the life cycles of a variety of yeast strains. Most yeast strains survive for about 30 or 35 generations of cell division. Each generation is represented by a mother cell s production of a new daughter cell, or yeast bud. The yeast cells were genetically modified to turn color if they started showing genetic instability. In every strain of yeast studied, genetic changes (mutations) started to develop at the equivalent of late-middle age in humans.
In following the life history of the cells, we found it takes about 25 generations, or cell divisions, to see an LOH event, Gottschling said. After that, the genetic instability just starts happening like crazy. We think a switch of some kind is being thrown, because it s happening in virtually all of the new offspring at the same time.
Even among the long-lived yeast that were genetically manipulated to go through 50 to 60 generations of cell divisions before dying, the evidence of DNA damage showed up, like clockwork, right around the 25th generation. This indicates that life span of a living organism has its own clock and does not depend on genetic instability. Living longer doesn’t necessarily mean you have fewer genetic mistakes. It just means you somehow live longer with more of them, said Gottschling.
The researchers surmised that genetic instability as such is not related to how close the cells are to death, but how far they are from birth how many times they have divided.
The discovery that an age-dependent switch is somehow activated to trigger genomic instability could have major scientific consequences, Gottschling said. This helps us to simplify. It gives us a place to focus to try and understand the causal event at the onset of cancer development.
If researchers can determine the molecular mechanics that trip the switch, they one day may be able to develop drugs or gene-replacement methods to prevent the switch from being thrown in the first place.
The researcher’s findings also may lead to a better understanding of the role of stem cells in cancer development, a subject of intense scientific interest. In tracking the life span of the mother-yeast cells, which are largely analogous to stem cells in humans, they found that the mothers retained their genetic integrity as they aged only their daughters inherited chromosomal defects.
If you think of mother cells as stem cells, then the discovery that the offspring of aging mother-yeast cells have an increased rate of genomic instability fits with the idea that age-associated effects on stem cells could relate to the age-associated increase in cancer. McMurray said.
If this evolutionary process is biologically conserved in human stem cells , Gottschling said, it could explain a lot of the age-induced diseases that happen in people.
So if cancer is an inherent consequence of aging, are lifestyle interventions to prevent the disease such as eating right, not smoking, and getting enough physical activities merely an exercise in futility May not be so. The experiments done in Gottschling s lab was equivalent to yeast feeding on steak and potatoes the cells were grown in a very rich, nutrient-dense environment. The researchers are now like to perform similar experiments in which the yeast will be grown in a very restricted diet to see whether they could delay the switch that triggers the genetic instability.
Aging is indeed a potent carcinogen. Consider these statistics from the American Cancer Society: Nearly 80% of cancers are diagnosed after age 55. After reaching late middle-age, men face a 50% chance of developing cancer, and women have a 35% chance. It is not well understood why cancer surfaces alter in life, although a multitude of scientific theories abound. This finding may provide scientists with a new tool to test these theories. Gottschling said.
source: cancerwatch.org
