The End of Aging?
A signal tower
Stanford scientists have concluded that the predominant theory of aging may be incorrect, or at best, incomplete.
Aging presently is understood as comprehensive and cumulative tissue damage due to oxidation, toxin absorption, disease and stress. We degrade like the rusting hull of an old ship.
However, a new study involving the roundworm c elegans conducted by biologist Stuart Kim has found that changes in genetic transcription herald the stages of aging. Since the nematode has a life span of only 2-3 weeks, it is easy to observe the entire life cycle.
Using microarrays - silicon chips that detect changes in gene expression - the scientists hunted 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 determine 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 stresses affected the genes that make the worms get old.
It appears that worm aging wasn't due to 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 bulk of the molecular differences between young and old worms."
While the complexity of the human organism may point to additional longevity factors outside of possible genetic drift, scientists can begin searching for this new aging mechanism in humans now that it has been discovered in a model organism.
"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."
Humans evolved so that energies are focused on certainty of growth to reproduction age rather than longevity. Once the initial mission of the organism in its environment is carried out, breakdowns in communication between genetic signal towers introduce gaps into the replicating code of life - and hence more errors as cells die and are replaced by new cells that draw information from the increasingly flawed codebase that is scattershot with lacunae. Up until now, natural selection would have been weighted heavily towards effective reproductive ability rather than lifespan. However, the environment no longer demands this tradeoff. It's straightforward to see how, with continuing research, we'll be living much longer by maintaining signal transcription integrity across the generations of replacement (or replicant) cells that are created every second in virtually every area of our bodies.
Source: Stanford University
Labels: aging, dna, elt3, kim, longevity, transcription