Breakthrough: Gray hair will soon be a thing of the past

A groundbreaking study from NYU Grossman School of Medicine has shed new light on the causes of gray hair. It also focuses on the unique properties of melanocyte stem cells (McSCs) found in hair follicles. 

The study reveals that as people age, McSCs lose their ability to move between growth compartments in hair follicles. This ultimately affects hair color. The research improves our understanding of the mechanisms underlying hair pigmentation. It also opens up the possibility of developing treatments to reverse or prevent graying in humans.

Published in the journal Nature on April 19, the study focused on cells present in the skin of mice and humans, known as McSCs. The maturation of these cells determines hair color. They continually multiply but remain nonfunctional unless they receive a signal to transform into mature cells responsible for producing pigments. 

The researchers discovered that McSCs exhibit remarkable plasticity. This means they can transition between different states of maturity as they move through the various compartments of a hair follicle.

Normal hair growth vs. maturing hair growth

During normal hair growth, McSCs continually transition between their most primitive stem cell state and the next stage of maturation. The next stage is the transit-amplifying state, depending on their location within the hair follicle. The compartments within the follicle expose the McSCs to varying levels of protein signals that influence their maturation.

However, as hair ages, sheds, and regrows repeatedly, an increasing number of McSCs become trapped in a stem cell compartment called the hair follicle bulge. Here, they remain immobile and unable to mature into the transit-amplifying state. Consequently, they do not return to their original location in the germ compartment, where WNT proteins would have stimulated their regeneration into pigment cells.

“Our study adds to our basic understanding of how melanocyte stem cells work to color hair,” said study lead investigator Qi Sun, PhD, a postdoctoral fellow at NYU Langone Health. She further noted that these newly discovered mechanisms suggest that a similar fixed-positioning of melanocyte stem cells might occur in humans. 

If this is the case, it could provide a potential pathway for reversing or preventing the graying of human hair. This would be accomplished by helping these “jammed” cells move again between developing hair follicle compartments.

Stem cells play a crucial role

Researchers have discovered that the plasticity of melanocyte stem cells (McSCs) plays a crucial role in maintaining hair color. The findings suggest that the loss of McSCs’ unique ability to move back and forth between growth compartments in hair follicles could be responsible for hair graying. 

The research team at NYU Langone Health found that other self-regenerating stem cells, such as those that make up the hair follicle itself, do not exhibit the plasticity observed in McSCs. These other cells typically move in only one direction along an established timeline as they mature.

“For example, transit-amplifying hair follicle cells never revert to their original stem cell state. This helps explain in part why hair can keep growing even while its pigmentation fails,” said study lead investigator Qi Sun, PhD, a postdoctoral fellow at NYU Langone Health.

The same research team had previously demonstrated that WNT signaling is necessary for stimulating McSCs to mature and produce pigment. They found that the hair germ compartment, located directly beneath the bulge, was exposed to WNT signaling at a rate many trillions of times higher than McSCs in the hair follicle bulge.

How the research was done

In their latest experiments, the researchers physically aged the hair of mice by plucking and forcing regrowth. They discovered that the number of hair follicles with McSCs trapped in the follicle bulge increased from 15% before plucking to nearly 50% after forced aging. These cells were unable to regenerate or mature into pigment-producing melanocytes.

The researchers determined that the stuck McSCs ceased their regenerative behavior due to the lack of exposure to WNT signaling. This impaired their ability to produce pigment in new hair follicles, which continued to grow.

Conversely, other McSCs that maintained their movement between the follicle bulge and hair germ retained their ability to regenerate as McSCs, mature into melanocytes, and produce pigment over the entire study period of two years.

“It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for graying and loss of hair color,” said study senior investigator Mayumi Ito, PhD, a professor in the Ronald O. Perelman Department of Dermatology and the Department of Cell Biology at NYU Langone Health.

“These findings suggest that melanocyte stem cell motility and reversible differentiation are key to keeping hair healthy and colored,” said Dr. Ito.

The research team plans to explore methods of restoring motility to McSCs or physically relocating them back to their germ compartment. There, they can produce pigment. For this study, the researchers employed cutting-edge 3D-intravital-imaging and scRNA-seq techniques. This allowed them to track cells in near-real-time as they aged and moved within each hair follicle.

This research contributes significantly to our understanding of the biology of hair pigmentation. It also holds promise for future therapeutic interventions to address hair graying, a common cosmetic concern for many individuals.

What we know about hair color

The presence of pigments produced by cells called melanocytes determines hair color. These are located within hair follicles. There are two main types of pigments that contribute to hair color: eumelanin and pheomelanin. 

Eumelanin is responsible for shades of brown and black hair, while pheomelanin produces yellow and red hues. The specific combination and concentration of these pigments determine an individual’s hair color.

Several factors influence hair color, including genetics, age, and environmental factors:

Genetics

Genes play a significant role in determining hair color. The regulation of melanocyte function, melanin production, and pigment transfer to hair shafts involves multiple genes. The interactions between these genes and the expression of the relevant proteins determine the color, shade, and intensity of hair pigments.

Age

Hair color can change over time due to age-related factors. As people age, the melanocyte stem cells (McSCs) in hair follicles gradually lose their ability to produce melanocytes. This leads to a decrease in melanin production. This results in the graying or whitening of hair as pigment production slows down or ceases altogether.

Environmental factors

Exposure to sunlight, chemicals, and other environmental factors can alter hair color. Ultraviolet (UV) radiation from the sun can cause hair to lighten or acquire a sun-bleached appearance. Hair dyes and other chemical treatments can also change the hair color temporarily or permanently. This occurs by depositing artificial pigments on the hair shaft or by altering the natural pigments.

Hormonal factors

Hormones can affect hair color in certain situations. For example, pregnancy and some hormonal imbalances can lead to changes in hair color.

Nutritional factors

A deficiency in certain nutrients, such as vitamins and minerals, can impact hair pigmentation. For example, a deficiency in copper may lead to premature graying.

Medical conditions

Certain medical conditions and medications can cause hair color changes. For instance, vitiligo, an autoimmune disorder, can result in a loss of pigmentation in the hair, leading to patches of white hair.

Hair color is a complex trait influenced by various factors. Researchers continue to study the genetic and molecular mechanisms underlying hair pigmentation. Understanding these processes can lead to potential treatments for hair color-related conditions, such as graying, as well as cosmetic applications.

Stem cells and their implications for human health and longevity

Stem cells are unique cells with the potential to develop into many different cell types in the body. They have the ability to self-renew, which means they can divide and produce more stem cells, and differentiate, which is the process of transforming into specialized cells with specific functions. 

Stem cells play a crucial role in the growth, maintenance, and repair of various tissues in the body. There are two main types of stem cells: embryonic stem cells and adult (or somatic) stem cells.

Embryonic stem cells

These stem cells are derived from the inner cell mass of a blastocyst, an early-stage embryo that is just a few days old. Embryonic stem cells are pluripotent, which means they can differentiate into any cell type in the body. Due to their pluripotency, they have great potential in regenerative medicine and tissue engineering.

Adult (somatic) stem cells

These stem cells are found in various tissues throughout the body, such as the bone marrow, skin, and brain. Adult stem cells are multipotent, which means they can differentiate into a limited number of specialized cell types related to their tissue of origin. They are responsible for repairing damaged tissues and maintaining the normal turnover of regenerative organs, such as blood, skin, and intestinal tissues.

There are also induced pluripotent stem cells (iPSCs), which are adult cells that have been reprogrammed to an embryonic-like state by introducing specific genes. iPSCs have a similar potential for differentiation as embryonic stem cells but do not raise the same ethical concerns since they are derived from adult cells.

Stem cell research has advanced significantly in recent years, leading to breakthroughs in our understanding of human biology and the development of new therapies for various diseases and conditions. Some of the applications of stem cells include:

Regenerative medicine

Stem cells can be used to replace damaged cells and tissues in conditions such as Parkinson’s disease, spinal cord injury, heart disease, and diabetes.

Drug discovery and testing

Stem cells can be used to develop disease models, allowing researchers to test the efficacy and safety of new drugs before they are tested on humans.

Understanding disease mechanisms

Studying stem cells can provide insights into the genetic and molecular basis of various diseases, helping researchers develop targeted treatments.

Cell-based therapies

Stem cells can be used to treat blood disorders, such as leukemia and lymphoma, through bone marrow transplantation.

Despite the significant potential of stem cells, there are also challenges and ethical considerations associated with their use, particularly concerning embryonic stem cells. Researchers continue to explore new methods for harnessing the potential of stem cells while addressing these concerns.

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