New research reveals the cause of gray hair

Study sheds light on McSCs function and how their decline might be reversed,
​opening doors to new treatments and deeper insights into aging

Stem cells hold the secret to regenerating tissue and maintaining youthful features. Yet, certain cells, such as melanocyte stem cells (McSCs), fail earlier than others, leading to visible signs of aging like gray hair.

Recent discoveries published in the journal Nature have shed light on how McSCs function and how their decline might be reversed, opening doors to new treatments and deeper insights into the biology of aging.
​
Understanding Hair Pigmentation and Stem Cell Function

McSCs, located within hair follicles, are key to hair pigmentation. These cells move between compartments of the follicle, toggling between stem cell and transit-amplifying states. This mobility allows them to self-renew and generate pigment-producing melanocytes. However, unlike other stem cells, McSCs exhibit a unique ability to reverse their differentiation.

Live imaging and single-cell RNA sequencing reveal that McSCs respond to local cues, such as WNT protein signals, which guide their differentiation. These signals are critical during hair follicle regeneration.

For instance, during the growth phase of hair follicles, McSCs migrate downward and differentiate into melanocytes that pigment the hair. However, with age, McSCs become stranded in the hair follicle bulge, losing their ability to regenerate and mature. This immobility leads to graying hair.

Research at NYU Grossman School of Medicine has shown that aging accelerates McSC depletion. In mice studies, physically aged by plucking and forced regrowth, nearly half of McSCs became trapped in the follicle bulge, up from 15% in younger specimens. These trapped cells failed to regenerate or mature into pigment-producing melanocytes. Conversely, McSCs that maintained their mobility continued to regenerate and produce pigment over a two-year period.

This phenomenon highlights the distinct nature of McSCs compared to other stem cells. While hair follicle stem cells move unidirectionally along a maturity timeline, McSCs uniquely oscillate between differentiation states. This plasticity is essential for maintaining hair pigmentation but appears to diminish with age.

“It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for graying and loss of hair color,” explains Dr. Mayumi Ito, senior investigator of the study. She adds, “Our findings suggest that motility and reversible differentiation are key to keeping hair healthy and colored.”

The Role of WNT Signaling and Future Directions

WNT signaling plays a pivotal role in McSC function. In earlier studies, this pathway was shown to stimulate McSCs to mature and produce pigment. However, the follicle bulge exposes McSCs to significantly fewer WNT signals compared to the germ compartment, where these proteins are abundant. This imbalance underscores the importance of cellular mobility for maintaining pigmentation.
​
To further explore these dynamics, the research team plans to investigate methods to restore McSC motility. “If we can physically move jammed cells back to their germ compartment or enhance their motility, we might prevent or reverse graying,” says Dr. Qi Sun, lead investigator of the study.

Potential approaches include using small molecules or other agents to encourage McSC movement. These interventions could not only preserve hair color but also provide insights into aging mechanisms in other tissues. McSC plasticity suggests that similar principles might apply to stem cells responsible for tissue maintenance and regeneration throughout the body.

Implications Beyond Hair Color

The implications of McSC research extend far beyond aesthetics. Stem cells are vital for tissue regeneration and are studied for their potential to treat various diseases. McSC findings could inform broader research into aging and regenerative medicine. For instance, understanding how to restore stem cell functionality could lead to therapies for conditions where cellular repair mechanisms falter, such as neurodegenerative diseases or certain cancers.
​
Despite their promise, stem cell therapies face ethical and safety challenges. Some worry about the use of embryonic stem cells, while others question the long-term safety of experimental treatments. However, advances in induced pluripotent stem cells—which do not rely on embryos—and rigorous clinical trials provide a path forward.

The research at NYU Grossman highlights the transformative potential of stem cell science. By uncovering how McSCs lose functionality and exploring ways to restore their mobility, scientists pave the way for innovative treatments.

These advancements not only address cosmetic concerns like graying hair but also deepen our understanding of aging and cellular regeneration. As the research progresses, it may unlock solutions for a wide range of age-related conditions.

Perception of Gray Hair in Society

The perception of gray hair in society has evolved significantly across cultures and historical periods, reflecting changes in attitudes toward aging, wisdom, and beauty.

Ancient and Historical Views:

• Symbol of Wisdom and Respect: In many ancient societies, gray hair was seen as a marker of experience and wisdom. For instance, in ancient Greece and Rome, elders with gray hair were often respected for their perceived knowledge and life experience. Similarly, Confucian values in East Asia emphasized filial piety, associating gray hair with dignity and authority.
• Religious and Cultural Significance: In some traditions, gray or white hair was linked to spiritual purity or divine favor. For example, in certain Native American cultures, gray-haired elders were revered as keepers of knowledge and spiritual guides.

Middle Ages to Early Modern Period:

• Practical Associations: During the medieval period, life expectancy was lower, and gray hair often indicated survival into an advanced age, which was itself seen as a rarity and an achievement.
• Shifts in Fashion and Beauty: In European Renaissance and Baroque societies, powdered wigs in white or gray shades became fashionable among the aristocracy, blending notions of sophistication, wealth, and age.

19th and Early 20th Century:

• Youth and Beauty Idealization: With the rise of industrialization and modern beauty standards, youthfulness began to be idealized, and gray hair became increasingly associated with aging and decline. Hair dyes emerged in the late 19th century, providing a means to conceal gray hair and maintain a youthful appearance.

Mid-20th Century:

• Stigma Around Aging: The post-war era saw a growing emphasis on youth in advertising and media, reinforcing negative connotations around gray hair. Both men and women began using hair dye in greater numbers to project vigor and relevance in professional and social settings.
• Professional Bias: Gray hair was sometimes viewed as a disadvantage in competitive industries, especially for women, where appearance often played a larger role in career progression.

Late 20th Century to Present:

• Empowerment and Reclamation: Beginning in the late 20th century, movements advocating for authenticity and self-acceptance challenged the stigma around gray hair. High-profile figures, such as celebrities and activists, began embracing their natural gray, sparking a cultural shift.
• Modern Beauty Trends: In the 21st century, gray hair has been redefined as a stylish and empowering choice. Fashion trends even popularized "silver hair" dye among younger generations, framing gray as a chic and deliberate aesthetic.
• Cultural Nuances: While gray hair is now widely accepted in some societies as a natural part of aging, other cultures continue to emphasize youth and may perceive gray hair differently.

​Today, gray hair is often celebrated as a symbol of confidence and individuality, signaling a broader acceptance of aging and natural beauty in many parts of the world. However, attitudes remain complex and vary depending on cultural, generational, and social factors.

The study's co-authors include Minwoo Kim, Bo Zhang, Vivian Lee, Bin Wu, Zhiwei Ma, Michael Peckerar, Luiza Baptista, Sadegh Davari, David R. Drummond, Jessica G. Yeh, and Elsa Quintana-Bustamante.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

from The Brighter Side of News