Exercise improves quality of life but not longevity in mice
Researchers at Karolinska Institutet have studied the effects of exercise in a mouse model of premature ageing. The study with fellow researchers from Harvard Medical School, was recently published in the journal Aging Cell.
“We find widespread disruption of protein levels in muscle and brain in mice with premature aging, and that the brain can cope better than the muscles. Voluntary exercise (access to running wheels) improves the quality of life of premature ageing mice: they lose less hair, become less hunched and move with more ease", says Lars Olson, Professor at the Department of Neuroscience, Karolinska Institutet.
A careful study of protein levels in muscle and two brain areas shows that exercise normalises the level of many proteins. The study also suggests that the degree of mutations decreases in the special mitochondrial DNA found in the cells' power plants, the mitochondria. This could mean that exercise might lead to healthier mitochondria by sorting out mitochondria with excessive mutations in their mtDNA, i.e. an improvement of the DNA that we have the most of in our body.
What are the most important results of the study?
In this mouse model of ageing we now show how voluntary exercise has dramatic rejuvenating effects inside out. Yet the mice do not live longer.
How could your study contribute to improving human health?
“Why exercise? The brain contributes very little to our body weight but requires 20% of the blood that a young heart is pumping out. Hence, we should strive to have a young healthy heart. Hence, we should exercise” says Lars Olson.
“We now show that disturbances of protein levels not only happen in skeletal muscles if we do not exercise, but also in the brain, and that these alterations are normalised by exercise. It is probably better for the brain to exercise that to solve cross words.”
How did you perform your study?
“We used a mouse model developed by professor Nils-Göran Larsson at Karolinska Institutet. This particular model tests the hypothesis that ageing is caused by failing mitochondria (the cells power plants), and that this is due to an increasing mutation load in the mitochondria's own DNA, i.e. mtDNA.”
There is a constant synthesis of new mtDNA, and in the "mtDNA mutator mouse" with premature ageing, there is impairment of the proof-reading required when new mtDNA is synthesized. Hence the mtDNA mutation load is progressively increasing in mitochondria in all cells of the body. This leads to premature, but otherwise strikingly typical, ageing changes including loss of hair, greying of hair, loss of subcutaneous fat, kyphosis, osteoporosis, enlarged heart, anemia, impaired hearing, decreased fertility, shrinking muscles, decreased body weight and size, and decreased life span.
“We let two mice (per cage) share a running wheel. They eagerly used the wheels at night, when mice are most active. After a couple of months, we could see that the mice with access to running wheels had aged less than those without running wheels.”
The researchers used proteomics, a very advanced way to identify and quantify large numbers of proteins from very small tissue samples, to measure protein levels in a leg muscle and in two areas of the brain. They found massive disturbances of protein levels in non-exercising mtDNA mutator mice. Interestingly, these disturbances were present but less severe in brain than in muscle. They also found that many of these disturbed protein levels were normalized in both muscle and brain by exercise.
Voluntary exercise normalizes the proteomic landscape in muscle and brain and improves the phenotype of progeroid mice.
Ross JM, Coppotelli G, Branca RM, Kim KM, Lehtiö J, Sinclair DA, et al
Aging Cell 2019 Sep;():e13029