File Name: genetics and reversal of early greying of hair .zip
This is an open access article distributed under the terms of Creative Commons Attribution License. Hair graying may be classified as natural senile canities and premature graying. Natural senile canities usually has its onset after the age of 40 years and aggravates with the ongoing aging process 1.
- 15 Facts That Will Change Everything You Think About Going Gray
- Premature graying of hair
- Premature Graying of Hair: Review with Updates
15 Facts That Will Change Everything You Think About Going Gray
This is an open access article distributed under the terms of Creative Commons Attribution License. Hair graying may be classified as natural senile canities and premature graying. Natural senile canities usually has its onset after the age of 40 years and aggravates with the ongoing aging process 1. Unlike senile canities, premature graying occurs prior to the age of 25 years and is usually progressive and permanent 2 , 3. Although hair graying is considered to be genetically controlled and inheritable, the underlying mechanisms have remained largely elusive 4.
Hair color is determined by pigment granules in hair follicles, wherein melanin synthesis is particularly crucial 5. Mature melanocytes are densely distributed in hair bulbs to sustain active melanogenesis, which is strictly coupled to the anagen stage of the hair cycle 6 , 7. The biosynthesis of melanin and its subsequent transfer from melanocyte to hair bulb keratinocytes is a rather complex process 8.
Polymorphisms within these loci are associated with a normal variation in hair color traits In addition, a genome-wide association study on the genetic basis of pigmentation in human subjects revealed that the single nucleotide polymorphism frequency distribution of these genes is linked to skin color and hair color 11 , A broader study indicated that mutations in two pore segment channel 2, agouti signaling protein and melanocortin 1 receptor are associated with hair color and pigmentation Previous studies have focused on identifying genes that encode characteristic markers for premature graying of hair.
A germline mutation in the syntaxin 17 gene of horses was recently identified to cause premature graying of hair 14 and telomerase reverse transcriptase mutation carriers may also present with premature hair graying Reverse transcription polymerase chain reaction RT-PCR arrays on the gene expression profiles of the hair bulge and hair bulb revealed a significant downregulation of melanogenesis associated genes [tyrosinase TYR , tyrosine related protein 1 TYRP1 , melanocyte inducing transcription factor, paired box gene 3 PAX3 and proopiomelanocortin] in unpigmented hair bulbs and a downregulation of marker genes typical for melanocyte precursor cells [PAX3, SRY-Box 10 SOX10 and dopachrome tautomerase in unpigmented mid-segments compared with their pigmented analogues.
Superoxide dismutase 3 transgenic mice exhibited premature aging, including hair graying, abnormal gait and a shortened life span Although previous studies provided candidate genes associated with hair graying, their results are limited due to the unavailability of related hereditary family members or an insufficient number of subjects to provide representative results According to the central dogma of genetics, the genotype affects the phenotype through gene expression.
Thus, it is straightforward to assume that a variance in gene expression between the grey and black hair follicles underlies the difference in hair color. However, to the best of our knowledge, no previous study has assessed premature hair graying from this genetic aspect. In the present study, an RNA sequencing RNA-seq analysis was performed to reveal gene expression changes between grey and black hair follicles from Han Chinese patients suffering from premature hair graying.
It was intended to unravel the underlying mechanisms and potential candidate genes responsible for hair pigmentation loss. A total of 5 unrelated Han Chinese donors who presented with premature graying since they were teenagers and had a clear family history of premature hair graying were enrolled in the present study.
Their details are specified in Table I. The ratio of Fragments per kilobase per million of grey to black hair was calculated and differential expression genes were then studied by log2FC.
Functional classification and enrichment analysis of the DEGs were performed using the online platform of the Database for Annotation, Visualization and Integrated Discovery Total RNA was extracted from each hair follicle sample. The primers used are listed in Table II. The number of raw sequenced reads for each sample ranged from In order to identify genes with a role in premature hair greying, the samples were classified into a grey hair group and a black hair group, and the gene expression changes were compared between them.
In order to confirm these DEGs, the changes in their expression were also assessed for each subject individually. Most of these DEGs were changed in the same direction among the individual subjects Fig. DEGs between black and white hair follicles. B Heatmap of gene expression changes between black hair and white hair follicles in each subject. Each line represents a gene, each column represents the number per subject, and the colour of the heat map denotes the expression ratio.
Functional categories of DEGs between white and black hair follicles. Circle size represents the number of genes the larger the circle size, the higher the number of genes. The lowest number of genes in C and D were four and five, respectively. To determine the functional roles of these DEGs, the functional categories they were involved in were then examined.
Of note, the DEGs were mainly enriched in functional categories closely linked to pigment synthesis or metabolic pathways Fig. The DEGs were also known to be located in pigment granules and melanosomes Fig. Of note, genes associated with the nervous system accounted for the largest number of DEGs, although the significance of their enrichment was not as high as that in the categories associated with pigmentation. This may imply a disturbance of the nervous system in grey hair follicles compared with that in black ones.
This suggested that pathways involved in melanin biosynthesis are downregulated in grey hair follicles. Genes associated with pigmentation and melanin synthesis are predominantly decreased in white hair follicles. The height of the inner bars indicates the significance of the corresponding terms -logadjusted P-value , and the color corresponds to the enrichment Z-score GOplot.
The outer ring displays scatterplots of the expression changes log2 FC for genes in each term, wherein blue represents decreased expression. Of note, most of the miR-encoding DEGs 11 out of 13 had the other DEGs as their predicted targets Table III , the majority of which were significantly decreased in grey compared with black hair follicles.
Furthermore, among the miR-targeted DEGs, two genes syndecan binding protein and KIT are involved in pigment-associated pathways 26 , Another category of regulators affecting gene expression changes are TFs.
Transient receptor potential cation channel subfamily M member 1 TRPM1 , which encodes a permeable cation channel that is expressed in melanocytes and has a role in melanin synthesis, was among the downregulated genes regulated by these TFs 28 , Of note, SOX10 have been proved to have the ability to drive the differentiation of melanocytes Differentially expressed genes targeted by differential expression of genes encoding transcription factors RUNX3 and sex-determining region Y box A protein usually interacts with other proteins to function properly.
However, they may affect the melanin biosynthesis process and ultimately affect hair pigmentation through interacting with genes directly involved in melanin biosynthesis. DEG, differentially expressed gene. As presented in Fig. The results indicated that the expressional changes of all of these genes were consistent with those detected by RNA-seq analysis, thus confirming that all genes were consistently downregulated in grey vs. Validation of 9 differentially expressed genes in white vs. RNA was extracted from the gray and black hair of 10 patients.
A total of 10 columns present the log ratio. Nine genes are selected for quantitative analysis. Hair graying, particularly premature hair graying, changes the appearance of affected individuals in a mostly undesired manner and has attracted the attention of researchers. To date, the underlying causes have remained largely elusive. In the present study, a genome-wide RNA-seq profiling analysis was performed using grey and black hair follicles from the same individuals with premature hair graying.
It was revealed that pigment synthesis pathways were significantly impaired in grey vs. The present results support the theory that premature graying may occur due to exhaustion of the melanocytes' capability to produce hair pigmentation. Previous studies have suggested that premature hair graying is associated with factors affecting melanogenesis, including nutritional deficiencies 32 , insufficient neuroendocrine stimulation 33 and ionic signaling across melanosomes The identified DEGs included those with similar functions with this regard, e.
Of note, the present study identified that GJB1 was downregulated in grey vs. Of note, all of the 13 DEGs encoding miRs identified in the present study were significantly upregulated in grey hair follicles, indicating a substantial increase in the abundance of the corresponding mature miRs. Furthermore, the majority of the DEGs predicted to be targets of these miRs were significantly decreased in grey hair follicles, which is in line with the known mechanism that miRs reduce the expression of their target genes.
Another reason could be the decreased TFs in grey hair follicles. It has been reported that SOX10, in synergy with early growth response 2, may activate GJB1 in melanocytes, which may cause and alteration in melanogenesis 38 , Another point worth mentioning is that a relatively high fraction of DEGs was associated with the nervous system, including potassium voltage-gated channel subfamily Q member 2, basic helix-loop-helix family member e41, prostaglandin D2 synthase and centrosomal protein of kDa, which are thought to be involved in controlling the circadian rhythm.
Defects in these genes have been reported to be associated with a short sleep phenotype 40 , It is widely accepted that nerve signaling defects, including a disturbed sleeping ability, may lead to hair graying, which probably functions through its further effects on the nervous system and downstream pigmentation pathways While it remains elusive whether and how the nervous system contributes to premature hair graying, the present results may indicate a novel aspect regarding the causes of hair graying.
Since hair graying has been considered to be associated with aging of the hair follicle pigmentation system 43 , the JenAge Ageing Factor Database 44 was searched for the DEGs in grey hair identified in the present study. In conclusion, the present study was the first, to the best of our knowledge, to perform a genome-wide transcriptome profiling of human hair follicles affected by premature hair graying, which uncovered that damage of the melanin biosynthesis pathway was the direct cause of the decline hair pigmentation and the resulting hair graying.
Furthermore, it was indicated that deregulated miRs and TFs, as well as neural disturbances, may be underlying causes. The present study provided multiple clues worthy of subsequent study to elucidate the mechanisms underlying canities and human premature hair graying.
However, the present study is limited as only the processes occurring in subjects with premature hair greying were assessed, while the genetic predisposition to hair greying was not be determined. The genetic differences between subjects with premature hair greying and normal individuals should be assessed to identify the genes that are the primary cause of this condition.
The present study was supported by the National Natural Science Foundation grant no. GW analyzed transcriptome data. YB and GW wrote the paper.
All authors read and approved the final version of the manuscript. The present study was performed according to the declaration of Helsinki and was approved by the Research Ethics Committee at Fudan University Shanghai, China. Informed consent was obtained from each participant prior to enrollment.
Br J Dermatol. Tobin DJ: Human hair pigmentation-biological aspects. Int J Cosmet Sci. Exp Gerontol. Pandhi D and Khanna D: Premature graying of hair. Indian J Dermatol Venereol Leprol. J Invest Dermatol. Slominski A, Paus R and Costantino R: Differential expression and activity of melanogenesis-related proteins during induced hair growth in mice.
Tobin DJ: The cell biology of human hair follicle pigmentation. Pigment Cell Melanoma Res.
Premature graying of hair
Taking care of your brain health may be easier than you think! Visit Staying Sharp to learn more. Known by scientists as canities or achromotrichia, the graying of hair is a long-studied phenomenon that has a variety of causes. First, the good news: It's not going to kill you. Hairs appear to the naked eye as white, silver or gray absent the pigments that otherwise provide color in shades of black, brown, blond or red. Within each hair follicle are cells, known as melanocytes, that produce one of two basic pigments — eumelanin or pheomelanin, depending on your DNA. Eumelanin is commonly present in black and brown hair, while pheomelanin is found in red, auburn and blond hair.
Premature graying of hair PGH is defined as graying of hair before the age of 20 years in Caucasians and before 30 years in African American population. It can severely affect the self-esteem of an individual. The exact etiopathogenesis remains unknown, although it has been associated with premature aging disorders, atopy, and autoimmune diseases. Patients, who present with PGH, should be assessed for syndromes and metabolism diseases. Hair dyes remain the main modality of the treatment for cosmetic concerns after nutritional supplementation.
Intricate coordinated mechanisms that govern the synchrony of hair growth and melanin synthesis remain largely unclear. These two events can be uncoupled in prematurely gray hair, probably due to oxidative insults that lead to the death of oxidative stress-sensitive melanocytes. In this study, we examined the gene expression profiles of middle bulge and lower hair bulb segments that had been micro-dissected from unpigmented and from normally pigmented hair follicles from the same donors using quantitative real-time RT-PCR qPCR arrays. These data provide the first clear evidence that compromised antioxidant activity in gray hair follicles simultaneously affects mature hair bulb melanocytes and their immature precursor cells in the bulge region. This is an open-access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Premature Graying of Hair: Review with Updates
Click on image for details. Correspondence Address : Dr. With chronological aging, hair turns gray. Untimely premature hair graying PHG may tremendously influence on cosmesis, self-credibility, and social life of the affected individuals.
We include products we think are useful for our readers. If you buy through links on this page, we may earn a small commission. Learn why and when gray happens, but more importantly how to welcome this new silvery shade in your life! Going gray is commonly explained as a loss of pigment aka melanin in the hair shaft. Typically, this hair has a different feel and texture than its pigmented counterparts.
We include products we think are useful for our readers. If you buy through links on this page, we may earn a small commission. Gray hair is commonly associated with stress, heredity, and aging. Just like skin, your hair gets its natural color from melanin — without it, your hair would be white. When melanin production starts to slow down, you may start seeing gray hairs.