Human Hair Graying is Naturally Reversible and Linked to Stress

Background

 Hair graying is a process that worries most people. Although we know that graying associated with ageing is induced by a dearth of melanocyte stem cells and some oxidative damage to the follicles, further details remain fuzzy¹.

Hair graying occurs prematurely in some individuals, and has been associated with stress^2,3. There are also cases where gray hairs regain their original dark colours, producing a two-toned hair. The mechanisms behind these age-independent graying and reversal events have not been well-studied. This preprint aims to characterise the proteomic signatures of graying hair and investigate the links between stress and graying.

Key findings

 The researchers started by plucking hairs from 14 individuals and simply observing them under a light microscope. They laid out the pigmentation profiles of different hairs and categorised them as dark, white and transition, with the last category representing hairs that were in the process of graying (i.e. distal ends were dark and proximal ends were gray).

To map out the proteomic signatures associated with different hair types (dark and white), the researchers plucked hairs of each type from age- and diet-matched individuals, processed the hair shaft samples and ran them through a liquid chromatography-mass spectrometry (LC-MS) platform. They performed the experiment twice, with two different LC-MS set ups in two different labs, to validate the findings.

In the first experiment, the white hairs showed an upregulation of proteins related to biosynthesis, energy metabolism, antioxidants and ribosome function. A significant fraction of these were mitochondrial proteins linked to metabolic regulation. The white hairs also showed some downregulation of lysosomal and secretory proteins, likely corresponding to the lack of melanin production in such hairs. These results were largely corroborated by the second, independently conducted LC-MS experiment, with some minor differences.

Between the two experiments, the common trends that the researchers pulled out were an enrichment for oestrogen signalling and metabolic regulation components in white hairs. To check whether this enrichment represented an upregulation of specific proteins and not a bulk increase, they quantified the mitochondrial DNA (mtDNA) in both dark and white hairs. The mtDNA amounts were similar in both hair types, confirming that it was not a bulk phenomenon but a targeted increase in certain proteins.

Having laid down some baseline characteristics for white and dark hairs individually, they turned to events of reversal, where a previously gray hair regained its original pigmentation. Using the rate of hair growth and pigmentation, they analysed the timescales of graying and reversal and found that both processed happened on the same timescales. This pointed to an active mechanism controlling the reversal and not a gradual regaining of pigment. They also found that instances of graying followed by reversal were synchronised in time across different points on the scalp, indicating spatiotemporal coordination of this phenomenon.

The scientists next investigated the links between stress and graying. They looked at hairs that had a gray region flanked by two dark regions, and used the growth rate of hair to approximately date the instances of graying and reversal. When individuals were asked to reflect on possible stressful events in the past, they found that periods of stress corresponded with the time at which graying occurred, and cessation of the stressful period corresponded with reversal of graying.

The authors rounded off with a model to replicate hair graying and found three major components contributing to the observed patterns – an “ageing factor” that accumulated over time, a “threshold” below which graying did not occur and a “stress factor” that compounded the ageing factor. The model also indicated that the transition to graying and subsequent reversal is tied to whether the hair is at the threshold or not, with reversals absent in gray hairs that were far beyond the threshold.

Why I like this preprint

 The researchers quantified something generally regarded as unquantifiable or difficult, and broke down something as nebulous as “effects of stress” on the physiological process of hair graying.

Conducting LC-MS experiments on samples like hair are notoriously difficult, as keratin contamination from the experimenter is an all-pervasive issue. The researchers addressed this conundrum by conducting the experiments with two set-ups and in two different labs.

Finally, this study reflects the multidisciplinary efforts required for such investigations, being a collaboration across the fields of psychiatry, biochemistry and molecular biology.

Questions

• The role of oestrogen signalling in hair graying appears to be a significant result from the proteomics assay. Does it indicate any sex differences (or lack thereof) in the hair graying process, given that the hair samples came from both males and females?
• Do the proteomic signatures of gray hair change between individuals with a few gray hairs and those with a full head of gray hair? For instance, once the hair is past the “threshold”, is there any further change in gene expression or are the initial changes sufficient?
• Is the coordination across the scalp only true for gray hairs that have undergone a reversal and does it only occur for stress-linked events? In general, hair graying seems to occur in a dispersed manner, but is that also coordinated to some extent or more arbitrary?

References

1. Tobin DJ. The cell biology of human hair follicle pigmentation. Pigment cell & melanoma research. 2011 Feb;24(1):75-88.
2. Zhang B, Ma S, Rachmin I, He M, Baral P, Choi S, Gonçalves WA, Shwartz Y, Fast EM, Su Y, Zon LI. Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature. 2020 Jan;577(7792):676-81.
3. Kumar AB, Shamim H, Nagaraju U. Premature graying of hair: review with updates. International journal of trichology. 2018 Sep;10(5):198.

Tags: ageing, hair, proteomics, stress

doi: https://doi.org/10.1242/prelights.21033

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