Dedifferentiation maintains melanocyte stem cells in a dynamic niche
https://www.nature.com/articles/s41586-023-05960-6
“Mammalian tissue regeneration largely depends on the capacity of adult stem cells to differentiate. Stem cell differentiation is generally viewed as unidirectional and follows the hierarchical model originally established through the study of haematopoietic stem cells9,10,11. This theory proposes that stem cells (undifferentiated state) have two distinct fates: one to sustain themselves through self-renewal and the second to produce transit-amplifying (TA) progeny (intermediate differentiated state) that ultimately give rise to functional differentiated cells during tissue regeneration12,13,14. In this model, the life-long durability of self-renewing tissues is typically sustained by a functionally and molecularly heterogeneous pool of stem and progenitor cells.
The organization of the McSC system, responsible for hair pigmentation, is thought to parallel that of hair follicle stem cells (HFSCs)5,6,7,8. McSCs are located in the bulge and hair germ (HG) area in telogen-phase hair follicles (HFs)4,5, where they are surrounded by HF epithelial stem cells (bulge cells)14 and progenitor cells (HG cells)15,16 that constitute to the McSC niche. At the onset of the anagen growth phase, McSCs regenerate differentiated melanocytes that migrate downwards into the hair bulb, where they produce pigment for the hair. Similar to HG epithelial cells, HG McSCs activate WNT signalling and undergo differentiation at the onset of regeneration7. Furthermore, McSCs in the bulge cycle more slowly than those in the HG during HF regeneration6. On the basis of these studies, McSCs in the bulge are postulated to represent long-term stem cells6. However, their distinct functions and self-renewal capacities have yet to be characterized. Despite the close relationship between HFSCs and McSCs, there are disparities in their durability over time: McSCs become exhausted earlier than HFSCs in most animals and humans, which results in hair greying during ageing1,2,3. The high prevalence of hair greying suggests that there may be specific disadvantages in the long-term maintenance of McSCs.“
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Also, good old stress contributes to greying too.
A 2020 Nature paper seemed to suggest that acute stress can permanently deplete melanocyte stem cells — not through adrenal hormones, but via norepinephrine released directly from sympathetic nerves.
That norepinephrine causes the stem cells to over-proliferate and exit the niche, which means no more pigment in future hair cycles… 
Separately, copper deficiency has also been linked to greying.
Tyrosinase — the key enzyme for melanin production — is copper-dependent, so low copper can impair pigment formation even if the melanocyte stem cells are still present. And since high zinc intake can interfere with copper absorption, it would then follow that excessive zinc could contribute to greying by tipping that balance.
Anecdotally, I subjectively observed more greying when I was supplementing zinc 50mg nearly every day and experienced improvement when I reduced that to 2-3 days a week.
That said, it’s worth noting that many if not most people are actually high in copper and low in zinc.
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I have been aware of the neccessity to balance zinc and copper to prevent hair graying for awhile. After experimenting with dosages I now take 25mg zinc (from 202,5 mg zinc gluconate) for 2 days and then 1 day copper 2mg (in the evening before sleep on an empty stomach). This gets both levels at the high end of the reference range for me.
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How high do you like your copper levels?
Total copper was 110 μg/dL on my latest test, reference range is 63.7-140.12 μg/dL. When I took zinc 25mg every other day alternating with copper 2mg every other day, it was 138 μg/dL and free copper was above the reference range.
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