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Image: Mitochondrial defects caused by rare genetic mutations cause increased metabolism in human cells
.
Although this helps with short-term survival, it comes at a high cost: the rate of cell aging accelerates
dramatically.
High metabolism may also be a key reason
why most cells degenerate with age.
Source: Columbia University Irving Medical Center (Martin Picard)
Why do cells, and humans, age? The answer may have a lot to do with mitochondria, the organelles
that provide energy to cells.
Although this idea is not new, there has been a lack of direct evidence
in human cells.
A team led by researchers at Columbia University has found that human cells with damaged mitochondria respond by speeding up and consuming more energy
.
While this adaptation, known as "supermetabolism," enhances the cell's short-term survival, it also comes at a high price: the rate at which cells age increases
dramatically.
"These findings were found in cells from patients with rare mitochondrial diseases, but they may also be associated with other diseases that affect mitochondria, including neurodegenerative diseases, inflammation, and infection, in addition, overmetabolism may be a key cause
of most cell degradation as we age.
"
It is thought that mitochondrial defects (impairs the conversion of food sources into usable energy) force cells to slow down their metabolic rate in an effort to conserve energy
.
However, by analyzing the metabolic activity and energy expenditure of cells from patients with mitochondrial disease, the researchers found that cellular energy expenditure with mitochondrial damage doubled
.
In addition, re-analyzing data from hundreds of patients with different mitochondrial diseases showed that mitochondrial defects also increase the cost
of living energy at the overall body level.
While this energy boosts cell functioning, it also lowers the cell's telomeres (the cap that protects the ends of chromosomes) and activates stress responses and inflammation
.
The net effect accelerates biological aging
.
"When cells consume more energy to make proteins and other substances necessary for short-term survival, they may steal resources from processes that ensure long-term survival, such as maintaining telomeres," said
Gabriel Sturm.
This high metabolic state may explain why patients with mitochondrial disease experience symptoms
such as fatigue and exercise intolerance.
"To compensate for the extra energy your cells expend, your body 'tells' you not to overwork in order to conserve energy
.
As people age and become less energetic, we may see the same dynamics
.
”
The study doesn't point to any new treatments for patients with mitochondrial disease that are currently untreatable, but it does reinforce current recommendations
for patients to exercise more.
"It seems counterintuitive because if you are more active, the more energy you expend, which may make your symptoms worse
," Sturm said.
But exercise is known to increase the efficiency
of the body.
For example, a person who runs consumes less energy to maintain basic physical activity
than a person who does not exercise.
”
Improving the efficiency of the body can reduce the energy expenditure of cells, improve fatigue and other symptoms, which may partly explain the health benefits
of exercise for people with mitochondrial diseases and other healthy people.
When looking for new treatments for mitochondrial diseases, researchers should focus on high metabolism
.
"While mitochondrial defects do impair a cell's ability to produce energy, energy deficiency may not be a major trigger
for disease.
Our research shows that these deficiencies increase energy consumption
.
To improve the therapeutic effect, we may need to target hypermetabolism
.
We need more research to determine whether this works
.
”
High metabolism is also common
in other diseases.
If increasing cellular energy expenditure plays a causal role in driving the aging process, targeting high metabolism may be one way
to improve fatigue, improve people's quality of life, and even slow down biological aging.