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.
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.”
The Latest on: Mitochondrial function
via Google News
The Latest on: Mitochondrial function
- Stealth Biotherapeutics to Present at Jefferies 2019 London Healthcare Conferenceon November 19, 2019 at 4:05 pm
Mitochondria, found in nearly every cell in the body, are the body's main source of energy production and are critical for normal organ function. Dysfunctional mitochondria characterize a number of ...
- UC Davis study identifies mechanism to rapidly repair leaky gut in monkeys with SIV infectionson November 19, 2019 at 1:30 pm
"To reverse the damage caused by HIV and to increase the efficacy of ART, it is important to restore mitochondrial function and to rapidly repair the gut epithelium and immune defense," said Satya ...
- Mitochondrial mixing mechanism critical for sperm production in miceon November 19, 2019 at 8:19 am
And just like their parent cells, mitochondria need quality-control mechanisms to maintain their DNA and preserve their normal function. One such mechanism is mitochondrial fusion. Though mitochondria ...
- Tracking inheritance of human mitochondrial DNAon November 19, 2019 at 4:43 am
and mitochondrial diseases are among the most common genetic disorders. They occur in one in 5,000 people and can cause a wide range of health problems, ranging from fatigue to developmental ...
- Monitoring mitochondria may make tumors more manageableon November 18, 2019 at 2:46 am
Researchers can study the function of mitochondria in live tumor cells to predict potential treatments for lung tumors. David Shackelford, an associate professor of pulmonary and critical care ...
- Mitochondrial deficits in human iPSC-derived neurons from patients with 22q11.2 deletion syndrome and schizophreniaon November 18, 2019 at 2:29 am
For example, gene expression alterations in postmortem neocortical pyramidal neurons suggest disruption of mitochondrial function 5, and other studies reported mitochondrial defects in neural ...
- Master regulator in mitochondria is critical for muscle function and repairon November 15, 2019 at 7:55 am
New research from the MitoCare Center at Thomas Jefferson University, in collaboration with the Center for Genetic Medicine Research at Children's National Health System in Washington D.C., has ...
- Mitocellular communication: Shaping health and diseaseon November 14, 2019 at 1:07 pm
mitochondria and nucleus need to communicate to ensure optimal cellular function. Moreover, mitochondria actively influence other cellular components such as the lysosomes, the endoplasmic reticulum ...
- Mitochondrial damage by α-synuclein causes cell death in human dopaminergic neuronson November 14, 2019 at 3:39 am
However, the consequence of mitochondrial aSYN localisation on mitochondrial structure and bioenergetic functions in neuronal cells are poorly understood. Therefore, we investigated deleterious ...
via Bing News