The Age of Onset and Rate of Graying appear to be hereditary traits, typically inherited in an autosomal dominant pattern. It is common to observe members of the same family experiencing similar premature graying. Although premature graying often occurs without any underlying pathology, it is likely inherited through the same autosomal dominant mechanism.
Premature graying is generally defined as graying before the age of 20 in Caucasians, before 25 in Asians, and before 30 in African populations. Premature graying has been associated with conditions such as pernicious anemia, hyperthyroidism or hypothyroidism, osteopenia, and various rare syndromes (e.g., progeria and pangeria). Furthermore, individuals with premature graying, without any other recognized risk factors, have been shown to have a fourfold increased risk of developing osteopenia compared to those without premature graying.
A study by Orr-Walker et al. found that individuals who experienced graying before their second decade of life had lower bone mineral density compared to the general population, with a significant correlation to familial osteoporosis. The researchers concluded that premature graying might account for a small proportion of the population variation in bone density, although other studies have questioned these findings.
The possible links between premature graying and cardiovascular disease remain less clear, as do associations between graying and androgenetic alopecia or facial wrinkles as additional risk factors for myocardial infarction.
Pathophysiology of Hair Graying
Loss of hair pigmentation is one of the most prominent signs of aging. Although it is noted that by the age of 50, 50% of men will have 50% gray hairs, the precise cellular and molecular mechanisms underlying this process remain incompletely understood.
Graying can affect individual hair follicles either through gradual pigment loss over multiple hair cycles or by complete loss of color within a single cycle. This phenomenon may reflect:
- Decreased activity of tyrosinase in melanocytes
- Impaired communication between keratinocytes and melanocytes
- Genetically determined depletion of melanocytes
- Defects in activation or migration of melanocytes
To date, studies have confirmed that pigment loss in hair follicles is primarily due to a marked reduction in active melanocytes within the bulbs of anagen-phase hair follicles. As a result, fewer melanosomes are incorporated into hair keratinocytes. Additionally, melanosome transfer appears to be disrupted, as keratinocytes lack melanin granules despite their proximity to melanocytes rich in melanosomes. This dysfunction in melanocyte-keratinocyte interaction is further evidenced by the presence of damaged melanin in the bulb and adjacent dermis. This abnormality arises either from defective melanosome transfer to keratinocytes or from an inability to maintain melanin due to melanocyte degeneration, ultimately leading to the absence of melanogenically active melanocytes in the bulb. Notably, gray hairs exhibit reduced dopa reaction (a marker of tyrosinase activity), while white hair bulbs show a negative dopa reaction.
However, although depletion or dysfunction of melanosomes and their stem cells (melanocyte stem cells) is evident, this does not appear to be the primary cause of hair pigmentation loss. Rather, the fundamental cause seems to be linked to mechanisms governing hair follicle growth and alterations in the hair follicle life cycle, as indicated by previous studies.
Effects on Hair Due to Loss of Pigmentation
Numerous researchers have reported morphological and mechanical differences between white (gray) and normally pigmented hairs. Anecdotal evidence suggests that gray hairs tend to be rougher, coarser, and more unruly compared to pigmented hairs. Indeed, gray hair often resists permanent or temporary color changes and dyeing, characteristics that align with alterations in the underlying hair structure. Aging of the hair follicle likely triggers a reprogramming of the progenitor keratinocytes to increase the production of medullary keratinocytes rather than cortical keratinocytes.
In fact, the medulla is often enlarged and thicker in gray and white hairs, forming a central cavity. The thickness and growth rate both in vitro and in vivo are higher for white hairs, which also have a coarser texture and are more difficult to manage. A recent study by Wood et al. demonstrated that depigmented hairs grow faster, increase in diameter, and develop greater cortical mass, possibly due to reduced oxidative stress. Under normal conditions, oxidative stress is chemically transferred from melanocytes to keratinocytes via Ca²⁺ ions.
Van Neste’s research showed that white scalp hairs grow at least 30% faster than pigmented hairs, while a case study by Nagl reported that white hairs in beards can grow up to 300% faster than pigmented hairs.
It is possible that melanin granules act as “regulatory systems” controlling the differentiation level and metabolic state of the cells. A very recent study by Gåspår et al. revealed that thyrotropin-releasing hormone (TRH) actively participates in hair follicle biology and acts as a neuroendocrine regulator of follicular pigmentation in situ. Additionally, Choi et al. (2011) reported increased expression of the FGF7 gene and accelerated hair follicle growth in “white” hair follicles.
Specifically, the expression of keratin-producing genes such as KRTAP and FGF7 was significantly elevated in follicles with white hairs, whereas the expression of negative regulators like FGF5 was reduced
Is Premature Hair Graying Permanent?
Several studies have shown that premature hair graying is potentially reversible, although spontaneous repigmentation of hair is rare. There have been isolated reports of hair repigmentation following anticancer radiotherapy or inflammatory conditions such as erythrodermic eczema, erosive candidiasis of the scalp, anthrax, and actinomycosis.
Additionally, temporary hair repigmentation has been reported after administration of high doses of para-aminobenzoic acid and the use of certain medications including verapamil, tamoxifen, cyclosporine, etretinate, levodopa, latanoprost, and arsenic. Similarly, cases of hair repigmentation have been documented after exposure to X-rays and PUVA therapy in patients with Sézary syndrome, in two patients with celiac disease, and in individuals with late-onset cutaneous porphyria.
Perhaps one day we will be able to control hair pigmentation more effectively.
Until then, we’ll just keep dyeing our hair…
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