
These photos show the hair loss and wrinkled skin after two months of doxycycline induction, and the same mouse a month later after doxycycline was stopped, allowing restoration of the depleted mitochondrial DNA.
Wrinkled skin and hair loss are hallmarks of aging. What if they could be reversed?
Keshav Singh, Ph.D., and colleagues have done just that, in a mouse model developed at the University of Alabama at Birmingham. When a mutation leading to mitochondrial dysfunction is induced, the mouse develops wrinkled skin and extensive, visible hair loss in a matter of weeks. When the mitochondrial function is restored by turning off the gene responsible for mitochondrial dysfunction, the mouse returns to smooth skin and thick fur, indistinguishable from a healthy mouse of the same age.
“To our knowledge, this observation is unprecedented,” said Singh, a professor of genetics in the UAB School of Medicine.
Importantly, the mutation that does this is in a nuclear gene affecting mitochondrial function, the tiny organelles known as the powerhouses of the cells. Numerous mitochondria in cells produce 90 percent of the chemical energy cells need to survive.
In humans, a decline in mitochondrial function is seen during aging, and mitochondrial dysfunction can drive age-related diseases. A depletion of the DNA in mitochondria is also implicated in human mitochondrial diseases, cardiovascular disease, diabetes, age-associated neurological disorders and cancer.
“This mouse model,” Singh said, “should provide an unprecedented opportunity for the development of preventive and therapeutic drug development strategies to augment the mitochondrial functions for the treatment of aging-associated skin and hair pathology and other human diseases in which mitochondrial dysfunction plays a significant role.”
The mutation in the mouse model is induced when the antibiotic doxycycline is added to the food or drinking water. This causes depletion of mitochondrial DNA because the enzyme to replicate the DNA becomes inactive.
In four weeks, the mice showed gray hair, reduced hair density, hair loss, slowed movements and lethargy, changes that are reminiscent of natural aging. Wrinkled skin was seen four to eight weeks after induction of the mutation, and females had more severe skin wrinkles than males.
Dramatically, this hair loss and wrinkled skin could be reversed by turning off the mutation. The photos below show the hair loss and wrinkled skin after two months of doxycycline induction, and the same mouse a month later after doxycycline was stopped, allowing restoration of the depleted mitochondrial DNA.
Little change was seen in other organs when the mutation was induced, suggesting an important role for mitochondria in skin compared to other tissues.
Among the details, the skin of induced-mutation 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 extrinsic aging of the skin in humans. The mice with depleted mitochondrial DNA also showed changed expression of four aging-associated markers in cells, similar to intrinsic aging.
The skin also showed disruption in the balance between matrix metalloproteinase enzymes and their tissue-specific inhibitor — a balance of these two is necessary to maintain the collagen fibers in the skin that prevent wrinkling.
The mitochondria of induced-mutation mice had reduced mitochondrial DNA content, altered mitochondrial gene expression, and instability of the large complexes in mitochondria that are involved in oxidative phosphorylation.
Reversal of the mutation restored mitochondrial function, as well as the skin and hair pathology. This showed that mitochondria are reversible regulators of skin aging and loss of hair, an observation that Singh calls “surprising.”
“It suggests that epigenetic mechanisms underlying mitochondria-to-nucleus cross-talk must play an important role in the restoration of normal skin and hair phenotype,” Singh said, who has a secondary UAB appointment as professor of pathology. “Further experiments are required to determine whether phenotypic changes in other organs can also be reversed to wildtype level by restoration of mitrochondrial DNA.”
Learn more: Scientists reverse aging-associated skin wrinkles and hair loss in a mouse model
The Latest on: Mitochondrial function
via Google News
The Latest on: Mitochondrial function
- Imaging technique proves effective in measuring mitochondrial dysfunction in motor neuron disease (MND)on January 13, 2021 at 3:46 am
A non-invasive imaging technique called 31-phosphorus magnetic resonance spectroscopy was used to assess mitochondrial function in patients with MND and could be used to measure the effectiveness of ...
- GenSight Biologics Announces Publication of Results from LUMEVOQ® RESCUE Pivotal Phase III Trial in AAO journal Ophthalmology®on January 12, 2021 at 11:32 pm
Newman, MD, lead author, RESCUE principal investigator and LeoDelle Jolley Professor of Ophthalmology and Neurology at the Emory University School of Medicine in Atlanta, GA, USA. “ The study confirms ...
- Mitochondria in Overdrive Linked to Glioblastomason January 12, 2021 at 5:00 am
Twenty percent of glioblastomas are found to be powered by overactive mitochondria and may be treatable with drugs in clinical trials.
- Study: 20% of glioblastomas are fueled by overactive mitochondriaon January 11, 2021 at 3:52 pm
A new study has found that up to 20% of glioblastomas--an aggressive brain cancer--are fueled by overactive mitochondria and may be treatable with drugs currently in clinical trials.
- One in five brain cancers fueled by overactive mitochondriaon January 11, 2021 at 9:27 am
A new study has found that up to 20% of glioblastomas—an aggressive brain cancer—are fueled by overactive mitochondria and may be treatable with drugs currently in clinical trials.
- New findings help explain how COVID-19 overpowers the immune systemon January 11, 2021 at 8:37 am
Seeking to understand why COVID-19 is able to suppress the body's immune response, new research from the USC Leonard Davis School of Gerontology suggests that mitochondria are one of the first lines ...
- Treating neurodegenerative diseases by boosting mitochondriaon January 11, 2021 at 8:29 am
A new partnership between the Sheffield Institute for Translational Neuroscience (SITraN) and Nanna Therapeutics will advance mitochondrial drug discovery research for neurodegenerative diseases.
- Platelets boost stem cell function through mitochondrial donationon January 7, 2021 at 7:44 am
Researchers at INSERM have gained new insights into the basic biology of mesenchymal stem cell function, and how platelets improved that function in an animal model of wound healing.
- High-Throughput Mitochondria Transfer Device Developedon December 31, 2020 at 1:00 pm
This approach enables researchers to study and potentially treat diseases such as cancer, diabetes, and metabolic disorders.
via Bing News