Programmed cell death and cancer are intimately linked
There's a downside to everything. When humans evolved bigger brains,
we became the smartest animal alive and were able to colonise the
entire planet. But for our minds to expand, a new theory goes, our cells
had to become less willing to commit suicide – and that may have made
us more prone to cancer.
When cells become damaged or just aren't needed, they self-destruct in a process called apoptosis. In developing organisms, apoptosis is just as important as cell growth for generating organs and appendages – it helps "prune" structures to their final form.
By getting rid of malfunctioning cells, apoptosis also prevents cells from growing into tumours. "Reduced apoptotic function is well known to be associated with cancer onset," says John McDonald of the Georgia Institute of Technology in Atlanta.
McDonald compared skin cells from humans, chimpanzees and macaques and found that, compared to cells from other primates, our cells are reluctant to undergo apoptosis. When exposed to apoptosis-triggering chemicals, human cells responded significantly less than the chimp and macaque cells. Fewer human cells died, and they did not change shape in the ways cells do when preparing to die.
"He has a sound experimental finding," says Todd Preuss of the Yerkes National Primate Research Center in Atlanta, Georgia. "What that means in the broader context is open to debate."
McDonald suggests that humans' reduced capacity for apoptosis could help explain why our brains are so much bigger, relative to body size, than those of chimpanzees and other animals. When a baby animal starts developing, it quickly grows a great many neurons, and then trims some of them back. Beyond a certain point, no new brain cells are created.
Human fetuses may prune less than other animals, allowing their brains to swell. "Natural selection for reduced apoptotic function only makes sense with respect to an increase in brain size," McDonald says. Proteins called executioner caspases are involved in apoptosis, and if these are turned off in mice, the animals grow enormous brains.
Skin cells are not neurons, cautions James Noonan of Yale University. "It remains to be seen whether this happens in the developing brain." Noonan says the idea shouldn't be dismissed, but he wants to see much more evidence.
When cells become damaged or just aren't needed, they self-destruct in a process called apoptosis. In developing organisms, apoptosis is just as important as cell growth for generating organs and appendages – it helps "prune" structures to their final form.
By getting rid of malfunctioning cells, apoptosis also prevents cells from growing into tumours. "Reduced apoptotic function is well known to be associated with cancer onset," says John McDonald of the Georgia Institute of Technology in Atlanta.
McDonald compared skin cells from humans, chimpanzees and macaques and found that, compared to cells from other primates, our cells are reluctant to undergo apoptosis. When exposed to apoptosis-triggering chemicals, human cells responded significantly less than the chimp and macaque cells. Fewer human cells died, and they did not change shape in the ways cells do when preparing to die.
Down-regulated genes
In 2009, McDonald found that genes promoting apoptosis are down-regulated – essentially suppressed – in humans, and those turning it off are up-regulated (Medical Hypotheses, doi.org/bgkshp). Genes involved in apoptosis are also known to have changed rapidly during human evolution. The new study adds to the evidence that apoptosis is down-regulated in human cells."He has a sound experimental finding," says Todd Preuss of the Yerkes National Primate Research Center in Atlanta, Georgia. "What that means in the broader context is open to debate."
McDonald suggests that humans' reduced capacity for apoptosis could help explain why our brains are so much bigger, relative to body size, than those of chimpanzees and other animals. When a baby animal starts developing, it quickly grows a great many neurons, and then trims some of them back. Beyond a certain point, no new brain cells are created.
Human fetuses may prune less than other animals, allowing their brains to swell. "Natural selection for reduced apoptotic function only makes sense with respect to an increase in brain size," McDonald says. Proteins called executioner caspases are involved in apoptosis, and if these are turned off in mice, the animals grow enormous brains.
Skin cells are not neurons, cautions James Noonan of Yale University. "It remains to be seen whether this happens in the developing brain." Noonan says the idea shouldn't be dismissed, but he wants to see much more evidence.
Bigger brains, longer lives
Preuss says that lower levels of
apoptosis could also help explain why humans live so much longer than
other primates, something that allows us to lavish time on raising
children and acquiring knowledge. "Animals with larger brains tend to
live longer," he says.
"The connection with cancer is really intriguing," Preuss adds. There isn't systematic data on cancer rates in non-human primates, but apes with tumours are rare. That suggests we might need to be careful about using animal models to study cancer. "Humans have modified our biology in ways people haven't taken into account," he says.
"The connection with cancer is really intriguing," Preuss adds. There isn't systematic data on cancer rates in non-human primates, but apes with tumours are rare. That suggests we might need to be careful about using animal models to study cancer. "Humans have modified our biology in ways people haven't taken into account," he says.
No comments:
Post a Comment