Grey hair and cellular senescence

Grey hair is hair that has lost its natural pigment, resulting in a colorless or silver appearance. It occurs due to a decrease in melanin production, the pigment responsible for hair color. Melanin is produced by specialized cells called melanocytes located in the hair follicles. As we age, these melanocytes can become less active or stop producing melanin altogether, leading to the growth of grey or white hair.

Grey hair usually appears gradually and can be more noticeable in individuals with darker hair. It often begins at the temples or along the hairline and then spreads to other areas of the scalp. However, the appearance and pattern of grey hair can vary significantly among individuals.

The reason why grey hair may appear in clusters or patches rather than uniformly is not fully understood. It could be influenced by various factors such as genetics, hormonal changes, and environmental factors. In some cases, certain medical conditions or treatments like chemotherapy can also cause clusters of grey hair to appear.

Senescence, or the appearance of senescent cells is most likely to be the culprit of grey cells appearing.

While genetics play a significant role in determining when and how much grey hair a person develops, other factors such as age, stress, and lifestyle choices can also contribute to the onset of greying hair. Embracing grey hair is a personal choice, and many people choose to embrace their natural hair color or use hair dyes to achieve the desired look.

Senescence and senescent cells

Senescence refers to a state of irreversible cell cycle arrest where cells lose their ability to divide and proliferate. Senescent cells can develop in various tissues and organs throughout the body, including hair follicles. Cellular senescence can be triggered by multiple factors, including DNA damage, telomere shortening, oxidative stress, and inflammation.

In the context of hair follicles, senescent cells play a role in the greying of hair. Hair follicles contain melanocytes, specialized cells responsible for producing the pigment melanin, which gives hair its color. As melanocytes age and undergo senescence, they produce less melanin, leading to a reduction in pigmentation and the appearance of grey or white hair.

The accumulation of senescent cells in hair follicles is believed to contribute to age-related greying. These senescent cells exhibit specific molecular and structural changes, including alterations in gene expression and the secretion of inflammatory molecules known as senescence-associated secretory phenotype (SASP) factors. The SASP factors released by senescent cells can affect the surrounding cells and tissues, potentially influencing hair follicle function and pigmentation.

Grey hair, therefore, can serve as an indicator of cellular senescence in hair follicles. The presence of grey hair suggests that a significant number of melanocytes within the hair follicles have entered a senescent state and are no longer producing melanin.

However, it’s important to note that greying hair is a natural part of the aging process and can be influenced by various genetic and environmental factors in addition to cellular senescence.

Greying hair is not necessarily an indicator of aging but it is a sign of gradual loss of melanin production and function in hair follicles

Understanding the mechanisms underlying cellular senescence and its effects on hair pigmentation may contribute to future advancements in treatments or interventions targeting age-related greying or hair loss.

Types of greying hair

There are primarily two types of greying hair: age-related greying and premature greying. Here’s how they differ:

  1. Age-Related Greying: Age-related greying is the natural process of hair turning grey or white as a person gets older. It typically occurs gradually over time and is influenced by genetic factors. Age-related greying is the most common type and is considered a normal part of the aging process. It is associated with the natural decline in melanin production by melanocytes in the hair follicles.
  2. Premature Greying: Premature greying refers to the greying of hair that occurs at a relatively young age, typically before the age of 30. This type of greying is not considered part of the normal aging process and can be influenced by various factors, including genetics, environmental factors, lifestyle choices, and underlying health conditions. Premature greying can occur in patches or affect the entire head of hair.

The underlying mechanisms of age-related and premature greying may share some similarities, such as the depletion or dysfunction of melanocytes in the hair follicles. However, premature greying often occurs due to a combination of genetic predisposition and external factors, while age-related greying is primarily influenced by the natural aging process.

It’s important to note that while grey hair is commonly associated with age-related greying, some individuals may experience grey hair at an early age due to factors other than premature greying, such as stress, certain medical conditions, or medical treatments.

How hair becomes grey from a cellular standpoint

The process of hair follicles turning grey is a complex interplay of genetic, epigenetic, and biochemical factors. While the exact mechanisms are not fully understood, the following steps provide an overview of the general process:

  1. Genetic and Epigenetic Influences: Genetic factors play a crucial role in determining the timing and extent of hair greying. Variations in genes related to melanin production and regulation, such as the melanocortin 1 receptor (MC1R) gene, can influence the susceptibility to premature greying. Epigenetic changes, such as modifications to the DNA or associated proteins, may also affect gene expression and contribute to greying.
  2. Melanocyte Function: Melanocytes are specialized cells located in the hair follicles responsible for producing the pigment melanin. Melanin gives hair its color and comes in two forms: eumelanin (black/brown) and pheomelanin (yellow/red). As we age, the activity of melanocytes can decline or become less efficient, leading to reduced melanin production.
  3. Oxidative Stress: Oxidative stress, which occurs when there is an imbalance between antioxidants and free radicals in cells, can damage melanocytes and interfere with melanin production. This oxidative damage can affect the functioning of melanocytes and contribute to the greying process.
  4. Decreased Enzyme Activity: Enzymes involved in melanin synthesis, such as tyrosinase, are essential for converting the amino acid tyrosine into melanin. As we age, the activity of these enzymes can decrease, leading to reduced melanin production.
  5. Accumulation of Hydrogen Peroxide: Another contributing factor to greying is the accumulation of hydrogen peroxide in the hair follicles. Hydrogen peroxide interferes with melanin production and can lead to the bleaching of hair color.
  6. Decreased Melanosome Transfer: Melanin is stored in structures called melanosomes, which are transferred from melanocytes to hair cells. As we age, the transfer of melanosomes from melanocytes to hair cells can become less efficient, leading to reduced pigmentation of the hair.

Overall, the process of hair greying is a complex interaction between genetic factors, epigenetic changes, oxidative stress, enzyme activity, and melanosome transfer. While these factors collectively contribute to greying hair, the exact sequence and relative importance of each step may vary among individuals.

The gradual loss of melanin production and function in hair follicles ultimately results in the appearance of grey or white hair.

Grey hair treatments

As of 2023, greying hair is generally considered a natural and irreversible part of the aging process. While there is no known cure for grey hair, some treatments and options may help address its appearance or temporarily restore color such as hair dyes, and similar hair touch-up products.

However, lifestyle changes, while not a direct treatment, maintaining a healthy lifestyle, managing stress, and consuming a balanced diet rich in vitamins and minerals may help support maintaining original hair color.

No pharmaceutical products have been able to conclusively establish a mechanism for restoring the original hair color to grey hair. However, there are some supplements that have been shown to improve the appearance of grey hair as a side effect and have the potential to be investigated in that regard.

To date, there have been about 30 studies discussing medication-induced gray hair repigmentation, including 6 articles on gray hair repigmentation as a primary objective, notably with psoralen treatment or vitamin supplementation, and 21 reports on medication-induced gray hair repigmentation as an incidental finding.

Incidental findings, so far have indicated that some treatments for inflammation, in particular, may hold the key to restoring original hair color.

Medications noted in the literature include anti-inflammatory medications (thalidomide, lenalidomide, adalimumab, acitretin, etretinate, prednisone, cyclosporin, cisplatinum, interferon-α, and psoralen),

Melanin production, the chemical responsible for hair color was also investigated in stimulators of melanogenesis (latanoprost, erlotinib, imatinib, tamoxifen, and levodopa),

Moreover, vitamins (calcium pantothenate and para-aminobenzoic acid), a medication that accumulates in tissues (clofazimine), and a medication with an undetermined mechanism (captopril). Diffuse repigmentation of gray hair can be induced by certain medications that inhibit inflammation or stimulate melanogenesis.

There is also low-quality evidence that some vitamin B complex supplementation can promote gray hair darkening. While these compounds are not currently indicated for the treatment of gray hair, their mechanisms shed light on targets for future medications for hair repigmentation.

PD-1/PD-L1 Inhibitors for Cancer Therapy was shown to have some notable effect on hair and hold promise also, so there is potential for hair repigmentation therapies.

Give it 3-4 years for grey-hair therapy to become properly studied, let’s hope it will be affordable if the appropriate findings live up to expectations.