It is almost always the case that measurement in biology is not as straightforward as the high level summaries make it out to be, and there is almost always some debate over whether the measurements are good enough, robust enough, and actually correct. Mitochondria are the power plants of the cell, conducting energetic reactions to produce the chemical energy store molecule adenosine triphosphate (ATP) needed to power the the cell. It is well established that mitochondrial function declines with age, but until quite recently measuring mitochondrial function required live mitochondria, which opened up all sorts of opportunities for cost, rework, bias, and error in the process of getting those mitochondria out of an animal (or person) and into a device in large enough numbers and good enough condition. Now, however a robust method for assessment in frozen samples exists, and researchers are putting it to good use, to double-check the present consensus on age-related mitochondrial decline.
It is generally accepted that mitochondria become less active in aging animals and that their dysfunction is a key contributor to the aging process. A device called a ‘respirometer‘ can be used to measure mitochondrial activity by detecting how much oxygen these organelles are consuming. However, until recently, this approach could only be applied to freshly isolated mitochondria obtained from mammalian tissues through a long and laborious process, making them difficult to study in large numbers. This limitation has prevented comprehensive analyses of mitochondrial respiration in mammalian tissues.
Using a recently developed protocol for respiratory analysis of frozen tissue samples researchers have now measured a proxy of mitochondrial respiration in over 1,000 samples from a large cohort of young and old mice of both sexes. This included tissues with reportedly high mitochondrial activity, such as certain brain regions, several skeletal muscles, the heart, and the kidneys. The samples also included metabolic tissues like the liver or pancreas, as well as sections of the gastrointestinal tract, the skin, and the eyes.
Due to the process of freezing and thawing, the mitochondria in the samples were not intact and therefore could not be isolated. Researchers measured mitochondrial respiration at three different sites on the electron transport chain in cellular extracts enriched with mitochondrial membranes. The proteins making up this chain are likely to remain relatively stable in mitochondria whose membrane integrity has been lost, which allows measurements that indicate the maximum capacity of the mitochondria to produce ATP to be taken.
Analyzing the differences between old and young animals revealed a net decline in mitochondrial activity in most tissues with age, most notably in samples from the brain and metabolic tissues. These results are consistent with our current understanding of the energetic demands of various tissues and how they decline over time. Intriguingly, in older animals, respiration increased in some tissues with high-energy demand, such as the heart and skeletal muscles, which is potentially at odds with the observation that these organs perform less well with age. Analyzing differences between samples from males and females also revealed that age has a much larger effect on mitochondrial activity across all tissues than sex.
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