Cancer, aging, and immortality
Dealing with immortal cells is all in a day's work for Dr. Karl Riabowol. Unfortunately, immortal cells usually point to cancer.
Our bodies are made up of more than 200 different kinds of cell, each type with its own set of replication instructions. Some cells, such as nerve and muscle cells, don't replicate at all once the organism has reached biological maturity. For others replication is an ongoing process; skin cells, for example, shed and replace themselves constantly. Then there are "immortal" cells, the kind that multiply with no sign of stopping.
As enticing as it might sound, however, this unrestrained growth of immortal cells is typically associated with cancer -making it a kind of immortality we're better off avoiding. AHFMR Scientist Dr. Karl Riabowol studies immortal cells in hopes of understanding how to suppress the growth of life-threatening tumours.
Dr. Riabowol spent several years studying and conducting research at the Cold Spring Harbor Laboratory in New York. Home to seven Nobel Prize winners, this private, non-profit research institution is renowned as one of the world's meccas for molecular biology. Dr. James D. Watson, one of the co-discoverers of the double-helix structure of DNA, spent nearly 40 years at this institution as its outspoken director, president, and chancellor.
Attracted by mountains, foothills, and a handsome AHFMR grant that would cover the cost of setting up and operating a new lab, Dr. Riabowol left New York for Alberta in 1991. Today he directs the Aging and Immortalization Laboratory in the University of Calgary's Faculty of Medicine.
When he first arrived in Calgary, Dr. Riabowol wanted to isolate genes that could act as growth inhibitors-what cancer scientists call "tumour suppressors". Using a new isolation procedure they had developed, Dr. Riabowol and his group had a breakthrough in 1996 with their discovery of a new tumour-suppressing gene: ING-1. The finding represented quite a feat in molecular biology, occurring as it did well before the human genome was published in 2001. ING-1 was not named after the financial institution; rather, the gene's name is derived from "INhibitor of Growth". As ING-1 began to demonstrate its ability to kill tumours, it stimulated a search for related genes. Dr. Riabowol subsequently discovered and named four more INGs: ING-2 to ING-5.
ING tumour suppressors are often "turned off" in certain cancers. This led Dr. Riabowol to ask questions from a different perspective: Do the cancers somehow know to target the cells that had their tumour suppressors turned off? And if these "brakes" to growth are not activated, does cancer formation necessarily follow? He also wants to know if normal aging cells use tumour suppressors to limit their growth.
In his search for answers, Dr. Riabowol hopes that the INGs discovered some 10 years ago will help him find clues to how aging relates to cancer formation. His lab also studies cell-lifespan regulators known as telomeres, tiny structures at each end of our chromosomes that appear to diminish in size each time a cell replicates. Like clocks ticking off seconds and minutes, telomeres count off the limited number of cell-replication events dictated by our genes.
Although he has not yet proven a definitive link between cell replication and human lifespan, Dr. Riabowol and his team have discovered that children conceived by older fathers have longer telomeres. This breakthrough is likely to have profound implications for society, since longer telomeres appear to be linked to longer-and probably healthier-lifespans, and might also protect against the emergence of cancer.
The idea of cancer as primarily a disease of aging hits home with just one telling statistic: Overall cancer incidence for people in their eighties is about 800 times higher than for people in their twenties. Dr. Riabowol was an early proponent of the view that cancer and cell aging are closely linked, and the concept is rapidly gaining credence in the scientific community today.
What are the potential implications as scientists around the world research this concept? Establishing how a person's age is linked to tumour suppression and cell immortality is the next step on the road to designing small multi-functional molecules for treating age-specific cancer in the future.