Why do cells, and by extension, humans, age? The answer may have a lot to do with mitochondria, the organelles that supply cells with energy. Though that idea is not new, direct evidence in human cells has been lacking.
In a study published on January 12 in Communications Biology, a team led by Columbia University researchers discovered that human cells with impaired mitochondria respond by kicking into higher gear and expending more energy. While this adaptation—called hypermetabolism—enhances the cells' short-term survival, it comes at a high cost: a dramatic increase in the rate at which the cells age.
"The findings were made in cells from patients with rare mitochondrial diseases, yet they may also have relevance for other conditions that affect mitochondria, including neurodegenerative diseases, inflammatory conditions, and infections," says principal investigator Martin Picard, PhD, associate professor of behavioural medicine (in psychiatry and neurology) at Columbia University Vagelos College of Physicians and Surgeons.
"In addition, hypermetabolism may be a key reason why most cells deteriorate as we get older."
It was generally assumed that mitochondrial defects (which impair the conversion of food sources into usable energy) would force cells to slow their metabolic rate in an effort to conserve energy. However, by analysing metabolic activity and energy consumption in cells from patients with mitochondrial diseases, the researchers found that cells with impaired mitochondria double their energy expenditure. Moreover, re-analysing data from hundreds of patients with different mitochondrial diseases showed that mitochondrial defects also increase the energetic cost of living at the whole-body level.
Although this energy boost keeps cells running, it also degrades the cell's telomeres (caps that protect the ends of our chromosomes) and activates stress responses and inflammation. The net effect accelerates biological aging.
"When cells expend more energy to make proteins and other substances essential for short-term survival, they're likely stealing resources from processes that ensure long-term survival, like maintaining telomeres," says Gabriel Sturm, a graduate student and lead author on this study.