DNA Discovery Reverses Appearance Of Age In Mice

Image source: UAB.

While we can’t yet live forever, we may soon be able to look like we haven’t aged a day. The further investigation of the role of mitochondrial DNA in the aging process has shown that a return of the mitochondrial DNA to its original state in mice can lead to a reverse in the appearance of age.

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What is the Mitochondrial Theory of Aging?

To understand how scientists planned to test anti-aging in mice, we need to look at the mitochondrial theory of aging. Mitochondria are organelles found in large numbers (hundreds to thousands) in each animal cell. Each mitochondrion contains its own DNA, called mitochondrial DNA. The mitochondrial theory of aging states that the accumulation of mitochondrial DNA mutations leads to faults in the mitochondrion, causing the organelle to malfunction and causing the appearance of aging.

Scientists created a mouse model that had been genetically modified to reduce the quantity of mitochondrial DNA present in the animals. Using the mouse model, the effects of the absence of mitochondrial DNA on aging and disease were studied.

Image source: Wikimedia Commons.

How Was the Theory Tested in This Study?

By introducing a mutation into the genome of the mouse model that can be “turned on”, or induced, scientists were able to produce transgenic mice that can express a mutation that reduces the quantity of mitochondrial DNA found in the animal by controlling the diet of the animal. In this case, the addition of doxycycline, an antibiotic, into the water and food of the transgenic mice turned on the mutation and led to the decrease in the normal amount of mitochondrial DNA in the mice.

In addition to the transgenic mice, scientists had two control groups of wild-type mice: one group which was fed the same diet as the transgenic mice, and the other group which was fed a normal diet. These controls allow the scientists to compare the transgenic model mice to normal (wild-type) mice, and to take into account any confounding effects from the diet.

What Were the Results?

Four weeks after the mutation had been turned on in the transgenic mice, the mice began to exhibit signs of aging. First, the mouse fur began to gray and thin, and the mice began to lose their fur. The mice then became slow and tired and began to develop thickened, wrinkly skin. Around six weeks after induction of the mutation, half of the mice died due to mitochondrial failure; the rest did not live longer than five months. While wild mice typically live only approximately six months, mice can live for up to two years.

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All of the mice showed signs of aging (fur loss, wrinkled skin) after two months of consuming doxycycline. After the doxycycline was removed from the food and water of the mice, the signs of aging slowly began to reverse. The skin became less wrinkled and thick, and the fur began to grow again. Within one month of the removal of doxycycline, the transgenic mice were similar in appearance to the normal wild-type mice.

What Does This Mean?

The presence of normal mitochondrial DNA appears to affect the appearance of an organism in terms of aging phenotypes. Possessing a healthy level of mitochondrial DNA allows the mitochondria to function normally, producing energy for cells. The study shows that mitochondrial function has a marked effect on the health and appearance of skin and hair follicles, and further work may show an effect on other organs as well.

Further Research

While the presence of mitochondrial DNA seems to largely affect the fur and skin of the mice, the effects should be more closely studied for other organs. It is possible that manipulations of mitochondrial DNA could restore other organs to healthier levels, but based on the evidence collected thus far, it seems that only the more superficial effects of aging (hair graying and loss, skin wrinkling, etc.) are reversible.

It is also important to note that, while the restorative effect of mitochondrial DNA levels on skin and hair has been observed in mice, the same effects may not also be observed in humans. One consideration to note is that this study very rapidly causes the reduction of mitochondrial DNA levels, which is unnatural. The reduction of mitochondrial DNA levels also does not mimic the natural accrual of mutations in the mitochondrial DNA. So while this study shows a link between the presence of normal levels of mitochondrial DNA throughout an organism and a healthy appearance, it does not take into account naturally slow rates of mutation and mutation accumulation. Further study is required to more fully understand the role of mitochondrial DNA in health and aging.

The development of the transgenic mouse model from this study and the results uncovered have increased our understanding of the role of mitochondrial DNA in aging and may allow for the advancement of therapies for mitochondrial diseases as well as skin and hair anti-aging treatments.

Bonus: A Related Study

In 2016, researchers in California found a way to eliminate mutated mitochondrial DNA from the organelles. By removing mutated mitochondrial DNA from cells, it may be possible to actually reverse aging. In this study, scientists manipulated an existing cellular pathway that identifies and causes the removal of mitochondria that are dysfunctional due to mutated mitochondrial DNA. However, this process does not seem to include the formation of any new mitochondria to replace the ones that have been removed. So, while the removal of dysfunctional mitochondria allows cells to operate more healthily, as mutations continue to accumulate in the remaining mitochondria causing those mitochondria to be removed, the overall number of mitochondria within each cell will diminish, surely leading to more rapid aging­. With careful regulation of the quality control of mitochondria based on mitochondrial DNA, it may be possible to prolong the healthy function of various organs as we age.

In conclusion, work studying mitochondrial DNA and its role in aging and disease have made progress in connecting the quantity and quality of the mitochondrial DNA to the appearance of aging, and ongoing studies will surely yield more exciting new discoveries in the aging area.

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Cite this article as:
Jessica McGregor. DNA Discovery Reverses Appearance Of Age In Mice, Science Trends, 2018. Available at:
http://doi.org/10.31988/SciTrends.24184
*Note, DOIs are registered Friday weekly and therefore may not work until then.

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