Age-related wrinkles and reverse hair loss in mice

Wrinkles and hair loss are perfectly natural aspects of aging – but science is about defeating nature who wants to kill us.

One aspect of aging is a decline in mitochondrial function.

Mitochondria – the energy factories of our cells – pushes nature back to the forehead. The researchers found that in a mouse model, when a mutation leading to mitochondrial dysfunction is induced, the mouse develops wrinkled skin and significant and visible hair loss within a few weeks. The mutation in the mouse model is induced when doxycycline antibiotic is added to food or drinking water. This causes depletion of mitochondrial DNA as the DNA replication enzyme becomes inactive.

But when mitochondrial function was restored by disabling the gene responsible for mitochondrial dysfunction, the mouse returns to the smooth skin and thick fur, indistinguishable from a healthy mouse of the same age.

The mouse on the center photo shows skin wrinkles associated with aging and hair loss after two months of depletion of mitochondrial DNA. This same mouse, right, shows the reversal of wrinkles and hair loss a month later, after resuming the replication of mitochondrial DNA. The mouse on the left is a normal control, for comparison. Credit: University of Birmingham Alabama

Importantly, the mutation that does this is in a nuclear gene affecting mitochondrial function, the tiny organelles known as cell power plants. Mitochondria produce 90% of the chemical energy that cells need to survive. When the doxycycline antibiotic was added to food or drinking water, it caused a depletion of mitochondrial DNA as the DNA replication enzyme becomes inactive. . In four weeks, the mice showed gray hair, reduced hair density, hair loss, slow motion and lethargy, changes that are reminiscent of natural aging. Wrinkled skin was observed four to eight weeks after induction of the mutation, and females had more severe skin wrinkles than males.

This hair loss and wrinkled skin were radically reversed by disabling the mutation. The photos below show hair loss and wrinkled skin after two months of induction of doxycycline, and the same mouse a month later after stopping the doxycycline, allowing the restoration of the 39: depleted mitochondrial DNA.

intrinsic and extrinsic aging – intrinsic aging is the natural process of aging, and extrinsic aging is the effect of external factors that influence aging, such as skin wrinkles that develop from the sun excessive or long-term smoking.

the skin of mutation-induced mice showed increased numbers of skin cells, abnormal thickening of the outer layer, dysfunctional hair follicles, and increased inflammation that appeared to contribute to skin pathology. These are similar to the extrinsic aging of the skin in humans. Mice with depleted mitochondrial DNA also showed a modified expression of four age-associated markers in cells, similar to intrinsic aging.

The skin also showed a disturbance in the balance between matrix metalloproteinase enzymes and their tissue-specific inhibitor – a balance of these two are needed to maintain collagen fibers in the skin that prevent wrinkling.

Mitochondria induced mutation-induced mice reduced mitochondrial DNA content, altered mitochondrial gene expression, and instability of large complexes involved in oxidative processes. phosphorylation.