Stress, DNA Damage Responsible For Grey Hair

Those stubborn grey hairs that come with age really are signs of stress, albeit of the cellular kind, according to a new Japanese study.

Genotoxic stress, which is anything that damages our DNA, sets off a chain reaction in which specialized cells known as melanocyte stem cells (MSCs) become damaged, ultimately resulting in a malfunction of the cells responsible for hair color.

Scientists discovered that the type of genotoxic stress that damages DNA depletes the MSCs in hair follicles that make pigment-producing melanocytes.   When exposed to the stress, these MSCs differentiate into mature melanocytes themselves, rather than dying off.  Therefore, anything that can limit genotoxic stress might also stop the graying from taking place, the researchers said.

“The DNA in cells is under constant attack by exogenously- and endogenously-arising DNA-damaging agents such as mutagenic chemicals, ultraviolet light and ionizing radiation,” said Emi Nishimura of Tokyo Medical and Dental University.
“It is estimated that a single cell in mammals can encounter approximately 100,000 DNA damaging events per day,” she added.

However, cells have sophisticated ways to repair damaged DNA and prevent the damage being passed on to their daughter cells.

“Once stem cells are damaged irreversibly, the damaged stem cells need to be eliminated to maintain the quality of the stem cell pools,” Nishimura explained.

“We found that excessive genotoxic stress triggers differentiation of melanocyte stem cells,” she said, adding that differentiation might be a more sophisticated way to eliminate those cells instead of fostering  their death.

Nishimura’s team had previously traced the loss of hair color to the gradual dying off of the stem cells that maintain a continuous supply of new melanocytes, which give hair its youthful color. It turns out that those specialized stem cells are not only lost, they also differentiate into fully committed pigment cells, and in the wrong place.

The current study, which used mice, found that irreparable DNA damage, in this case that caused by ionizing radiation, is responsible.  

Furthermore, the “caretaker gene” known as ATM (ataxia telangiectasia) serves as a stemness checkpoint that protects against MSCs differentiation, the researchers found.  That’s why people with Ataxia-telangiectasia, an aging syndrome caused by an ATM gene mutation, will gray prematurely.

The study supports to the idea that genome instability is a significant factor in aging.   It also supports the “stem cell aging hypothesis”, which says that DNA damage to long-lived stem cells can be a major driver for many of the conditions that come with age.

In addition to the aging-associated stem cell depletion typically seen in MSCs, quantitative and qualitative alterations to blood stem cells, cardiac muscle, and skeletal muscle have also been reported, the researchers said.  Stresses on stem cell pools and genome maintenance failures are also thought responsible for the decline of tissue renewal capacity and the accelerated appearance of aging-related characteristics.

“In this study, we discovered that hair graying, the most obvious aging phenotype, can be caused by the genomic damage response through stem cell differentiation, which suggests that physiological hair graying can be triggered by the accumulation of unavoidable DNA damage and DNA-damage response associated with aging through MSC differentiation,” the researchers wrote.

A separate study recently reported by European scientists found that going grey was caused by a build up of hydrogen peroxide due to normal wear and tear of the hair follicles.  The hydrogen peroxide blocked the normal production of melanin, the scientists wrote in the report, which was published by the Federation of the American Societies for Experimental Biology.

The current study was published in the June 12 issue of the journal Cell.

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