"Everyone has assumed we age by rust. But how do you explain animals that don't age? Some tortoises lay eggs at the age of 100, there are whales that live to be 200 and clams that make it past 400 years."

Stuart Kim, PhD, Stanford University professor of developmental biology and genetics

Prevailing theory of aging challenged by Stanford University Medical School researchers. Their discovery contradicts the prevailing theory that aging is a buildup of tissue damage similar to rust. The Stanford findings suggest specific genetic instructions drive the process. If they are right, science might one day find ways of switching the signals off and halting or even reversing aging.

“We were really surprised,” said Stuart Kim, who is the senior author of the research.

Kim’s lab examined the regulation of aging in C. elegans, a millimeter-long nematode worm whose simple body and small number of genes make it a useful tool for biologists. The worms age rapidly: their maximum life span is about two weeks.

Comparing young worms to old worms, Kim’s team discovered age-related shifts in levels of three transcription factors, the molecular switches that turn genes on and off. These shifts trigger genetic pathways that transform young worms into social security candidates.

The question of what causes aging has spawned competing schools, with one side claiming that inborn genetic programs make organisms grow old. This theory has had trouble gaining traction because it implies that aging evolved, that natural selection pushed older organisms down a path of deterioration. However, natural selection works by favoring genes that help organisms produce lots of offspring. After reproduction ends, genes are beyond natural selection’s reach, so scientists argued that aging couldn’t be genetically programmed.

The alternate, competing theory holds that aging is an inevitable consequence of accumulated wear and tear: toxins, free-radical molecules, DNA-damaging radiation, disease and stress ravage the body to the point it can’t rebound. So far, this theory has dominated aging research.

But the Stanford team’s findings told a different story. “Our data just didn’t fit the current model of damage accumulation, and so we had to consider the alternative model of developmental drift,” Kim said.

The scientists used microarrays—silicon chips that detect changes in gene expression—to hunt for genes that were turned on differently in young and old worms. They found hundreds of age-regulated genes switched on and off by a single transcription factor called elt-3, which becomes more abundant with age. Two other transcription factors that regulate elt-3 also changed with age.

To see whether these signal molecules were part of a wear-and-tear aging mechanism, the researchers exposed worms to stresses thought to cause aging, such as heat (a known stressor for nematode worms), free-radical oxidation, radiation and disease. But none of the stressors affected the genes that make the worms get old.

So it looked as though worm aging wasn’t a storm of chemical damage. Instead, Kim said, key regulatory pathways optimized for youth have drifted off track in older animals. Natural selection can’t fix problems that arise late in the animals’ life spans, so the genetic pathways for aging become entrenched by mistake. Kim’s team refers to this slide as “developmental drift.”

“We found a normal developmental program that works in young animals, but becomes unbalanced as the worm gets older,” he said. “It accounts for the lion’s share of molecular differences between young and old worms.”

Kim can’t say for sure whether the same process of drift happens in humans, but said scientists can begin searching for this new aging mechanism now that it has been discovered in a model organism. And he said developmental drift makes a lot of sense as a reason why creatures get old.

“Everyone has assumed we age by rust,” Kim said. “But then how do you explain animals that don’t age?”

Some tortoises lay eggs at the age of 100, he points out. There are whales that live to be 200, and clams that make it past 400. Those species use the same building blocks for their DNA, proteins and fats as humans, mice and nematode worms. The chemistry of the wear-and-tear process, including damage from oxygen free-radicals, should be the same in all cells, which makes it hard to explain why species have dramatically different life spans.

“A free radical doesn’t care if it’s in a human cell or a worm cell,” Kim said.

If aging is not a cost of unavoidable chemistry but is instead driven by changes in regulatory genes, the aging process may not be inevitable. It is at least theoretically possible to slow down or stop developmental drift.

“The take-home message is that aging can be slowed and managed by manipulating signaling circuits within cells,” said Marc Tatar, PhD, a professor of biology and medicine at Brown University who was not involved in the research. “This is a new and potentially powerful circuit that has just been discovered for doing that.”

Kim added, “It’s a new way to think about how to slow the aging process.” Via

Views: 92

Reply to This

Replies to This Discussion

To me, the only way that the aging could have evolved is if the individual recieves more benefit in terms of reproductive success (remember, it is defined as the number of offspring your offspring have) by ending their reproduction and instead help their offspring to reproduce successfully (ie, grandparents/alloparents). It is likely that at some point in our past grandparents played an important role in the raising of children, and without that help the total reproductive success of those grandparents would have been diminished.
I know I'm late, but remember that evolution doesn't tend to perfection. It tends to "good enough". Success is defined as the number of offspring your offspring have, but sheer numbers of offspring are not the only factor in succeeding. If you have a bunch of kids that all get eaten by lions, it's not successful. Either way, I'd propose aging to be more like an appendix. It can get infected and kill someone, but we still all have them because the penalty just isn't bad enough to make enough of a difference in success to change the whole population.
We seriously need to get population under control before fixing this age thing....
Either that or fix the 'need to eat' thing....

And just because something lives longer doesn't mean it doesn't age. A whale might have a longer lifespan, but it's still a finite one (even without disease or predators) therefore it still ages, just slower.
HA! I just love that you say what everyone is thinking but don't have the guts to mention. I'm just not sure how I feel about prolonging the lifespan of creatures that live like parasites.
How about finding a cure for dementia and Alzheimers, too? Cus as much as I'd love to be the perpetually crazy, perverted old lady toddling about, I'd hate to be surrounded by hundreds of them!
It's possible that research into aging will come up with a cure for dementia and Alzheimers, or vice-versa. Either way, if we're planning on having humans with multi-century lifespans, we are going to desperately need to expand out into the solar system for living space.

Giant orbital farms for growing food, immense space habitats, rotating with stately grace in the sun and star light.

Of course, we'll need to pull our collective heads out of our asses and stop trying to kill one another first.
I call Mars!
Given a few hundred years for terraforming (or some really overachiever microbes), Venus will be a nice place to live.

Four generations of a species per century can evolve four times faster than one generation per century. I'm guessing that tortoises reached a point in their evolution where a longer lifespan/reproductive period per tortoise outweighed the advantages of faster evolution, e.g. they were hitting an evolutionary dead end, and other similar species were not out-competing them.

Usually creature size largely affects lifespan, which makes sense from a birth-to-reproductive-adult time perspective. Bacteria (reproducing, say, every 20 minutes) and viruses can evolve very fast, but not whales or elephants.

Given that life expectancy can be optimally tuned by evolutionary factors (i.e. optimally timing death for newer generations to optimally continue the species), and given that we've pretty much out-innovated nature's evolutionary design for us, we should continue to be able to enhance lifespans and, more importantly, quality of life during the lifespan... if we can innovate for population control. But I would suggest we don't permanently tweak ourselves genetically, just in case we someday unexpectedly need to go back to evolving again in natural habitat.


© 2021   Created by Rebel.   Powered by

Badges  |  Report an Issue  |  Terms of Service