Why greying hair

The cells may wear out, become damaged, or lose the support systems meant to keep them working. Genes are also a factor, since they help control melanin production.

Scientists experimenting with mice recently showed that three specific genes can help maintain stable numbers of melanin-producing cells.

By manipulating the genes, the researchers prevented or reduced gray hair in the mice. But no product based on the research is currently available. Historical accounts claim jailed British statesman Sir Thomas More and French queen Marie Antoinette went white overnight while awaiting execution. Since the observed proteomic signatures are related to specific metabolic pathways rather than the typical high-abundance mitochondrial housekeeping proteins, we reasoned that the upregulation of these mitochondrial components unlikely reflects a bulk increase in total mitochondrial content.

The same was true in the follicles of the same hairs Figure 4—figure supplement 1. The similar mtDNA levels between dark and white HSs and HFs increases the likelihood that the reported proteomic changes reflect the induction of specific metabolic pathways associated with hair greying rather than bulk increase in mitochondrial mass. To identify a general proteomic signature of greying hair, we compiled the enrichment scores for KEGG pathways across all datasets Figure 4E.

Comparatively fewer pathways were consistently represented for downregulated proteins across independent experiments. In relation to hair biology in general, our data adds to previous efforts Franklin et al. Computing the cross-correlations for each protein pair revealed four main clusters among the HS proteome Figure 4—figure supplement 2. As expected for hair, keratins were well-represented and constituted the main GO biological processes category for three of the four clusters.

The top KEGG categories included glycolysis and estrogen signaling pathways, which also showed strong co-expression with each other, highlighting potential interaction among endocrino-metabolic processes in relation to human hair pigmentation.

In general, the identification of several non-keratin metabolism-related proteins in the HS opens new opportunities to investigate greying pathobiology and to non-invasively access past molecular and metabolic changes that have occurred in the aging HFPU of the dynamically growing hair.

Finally, to narrow the range of plausible mechanisms for the observed age-related greying and reversal events, we developed a simulation model of HPPs.

In the absence of such data, we propose here a mathematical model to simulate hair greying trajectories across the human lifespan Figure 5A , available online, see Materials and methods for details as has been attempted previously for hair growth cycles Halloy et al. As basic tenets for this model, it is established that i the onset of human hair greying is not yet underway and rarely begins in childhood, ii greying routinely starts between 20 and 50 years of age, iii greying is progressive in nature the total number and percentage of grey hairs increases over time , and iv the proportion of white hairs reaches high levels in old age, although some hairs can retain pigmentation until death, particularly among certain body regions Trueb and Tobin, Additionally, our findings demonstrate that v age-related greying is naturally reversible in isolated hair follicles, at least temporarily and in individual HS, and may be acutely triggered by stressful life experiences, the removal of which can trigger reversal.

A Schematic overview of the average greying process across the lifespan involving the gradual loss of pigmentation, or accumulation of white hairs, mostly in the second two-thirds of life.

B Depiction of individual hairs each line is a hair, i from a linear mixed effects model with random intercept and slopes predicting hair greying. The model assumes i a constant increase in a putative aging factor and ii a constant threshold above which hairs undergo depigmentation.

All model parameters are listed in Supplementary file 4. D Frequency distributions of grey hairs for individuals with early left , average middle , or late right hair greying phenotypes. E Single hair-level and F hair population-level results from the addition of two acute stress periods each one year in duration, occurring at ages 20 and The optimized model accounts for stress-induced greying in hairs whose aging factor is close to the depigmentation threshold, but not for young hairs or those far away from the threshold.

Similarly, the removal of the stressor causes repigmentation of hairs when the aging factor returns below the threshold. For modeling purposes, the accumulation of the aging factor is equivalent to the inverse of the decrease in a youth factor e. Based on the mosaic nature of scalp HFs and our data indicating that not all hairs are in perfect synchrony, the proposed model for an entire population of hairs must also allow a variety of aging rates, as well as differential sensitivity to stress among individual hairs.

However, some individuals also develop hairs with intermediate pigmentation states i. This represents a limitation to be addressed in future research.

A higher rate of accumulation of the aging factor higher slope for each hair or a lower threshold naturally accounts for earlier onset of greying. In addition, our model reveals that within a person, greater hair-to-hair heterogeneity in the rate of aging between HFs, modeled as the standard deviation of slope across hairs, also influences the onset of greying.

Greater heterogeneity between HFs allows for earlier onset of greying, whereas decreasing hair-to-hair variation i. Interestingly, this unpredicted result aligns with the notion that increased cell-to-cell heterogeneity is a conserved feature of aging Bahar et al.

Using parameter values that yield the average onset and rate of greying, we then simulated the influence of acute psychosocial stressors, either early in life before the onset of greying, or later once grey HSs have begun to accumulate. Similar to our data, the model also predicts transitory, or temporary reversible events of greying see Figure 3D.

Transitory greying events do not affect all hairs, only those that are close to the threshold at the time of stress exposure undergo greying. Hairs whose cumulative aging factors are substantially lower than threshold do not show stress-induced greying a 5-year-old is unlikely to get grey hairs from stress, but a year-old can Figure 5E—F. Similarly, grey hairs far above threshold are not affected by periods of psychosocial stress.

Thus, our model accounts for both the overall hair greying dynamics across the lifespan, and how a stressor or its removal may precipitate or cause reversal of greying in hairs whose aging factor is close to the greying threshold.

Extending our high-resolution quantitative digitization approach to hundreds of randomly sampled dark non-transitioning hairs from different scalp regions in the same individuals, we also show that fully dark i. This may in part be influenced by the migration of stem cells during embryogenesis to different parts of the scalp, or by other unknown factors. This preliminary extension of the HPP methodology provides a foundation for future studies. Moreover, the regional segregation of HPPs may reflect well-recognized regional differences in the rate of HS formation Robbins, Thus, future models may also be able to leverage information contained within HPPs from non-greying hairs and make specific inference from hairs collected across scalp regions.

Similar to how decoding temporal patterns of electroencephalography EEG provides information about the state of the brain, our data make it imaginable that decoding HPP analysis over time may provide information about the psychobiological state of the individual.

Our approach to quantify HPPs demonstrates rapid greying transitions and their natural transitory reversal within individual human hair follicles at a higher frequency and with different kinetics than had previously been appreciated. The proteomic features of hair greying directly implicate multiple metabolic pathways that are both reversible in nature and sensitive to stress-related neuroendocrine factors. Therefore, this result provides a plausible biological basis for the rapid reversibility of greying and its association with psychological factors, and also supports the possibility that this process could be targeted pharmacologically.

Melanogenesis is also known to both involve and respond to oxidative stress, a byproduct of mitochondrial metabolic processes Balaban et al. Moreover, alterations in energy metabolism are a major contributor to other disease-related aging features Kennedy et al. The upregulation of specific components related to mitochondrial energy metabolism in white hairs suggests that energy metabolism regulates not only hair growth as previously demonstrated Flores et al.

Approaches combining both high molecular and spatial resolution may be particularly informative Vyumvuhore et al. In vivo, exposing aged mice to young blood in parabiosis experiments Rebo et al. In human cells, quantitative biological age indicators such as telomere length Puterman et al. Moreover, the reversibility of greying in aging human HFs demonstrated by our data is also consistent with the observed reversibility of human skin aging in vivo when aged human skin is xenotransplanted onto young nude mice Gilhar et al.

Therefore, our HPP data and simulation model adds to a growing body of evidence demonstrating that human aging is not a linear, fixed biological process but may, at least in part, be halted or even temporarily reversed. Our method to map the rapid weeks to months and natural reversibility of human hair greying may thus provide a powerful model to explore the malleability of human aging biology within time scales substantially smaller than the entire lifespan.

A notable finding from both proteomics experiments is the bias toward up regulation rather than the loss of proteins in depigmented grey HS. As noted above, this may reflect the fact that hair greying is an actively regulated process within the HPFU, and that aging is not marked by a loss, but rather an increase in heterogeneity and biological complexity Bahar et al. Relative to the youthful state, quiescent and senescent cells exhibit upregulation of various secreted factors van Deursen, , as well as elevated metabolic activities Lemons et al.

Moreover, similar to the macroscopic appearance of hair greying, age-related senescence markers naturally occur stochastically for DNA methylation changes across the genome Franzen et al. Our data reveal that the conserved principle of an age-related increase in molecular and cellular heterogeneity is reflected not only at the tissue level mixture of dark and white hairs but also in the greying hair proteome.

Moreover, our proteomics results are also in line with recent reports of keratin-associated proteins that are downregulated in white vs dark hairs Giesen et al. Specifically, of a previously identified group of 50 potentially age-related, upregulated proteins in the HS Plott et al. Of these 16, 14 were similarly upregulated in depigmented white hairs relative to dark hairs from the same individuals in our dataset Supplementary file 2.

Further work will be required to determine if specific molecular aging processes, in specific cell types within the HF, account for the visible macroscopic instability of HFs greying on the human scalp.

Here, we provided proof-of-concept evidence that biobehavioral factors are linked to human hair greying dynamics. Our optical digitization approach thus extends previous attempts to extract temporal information from human hairs and illustrate the utility of HPP profiling as an instructive and sensitive psychobiology research model.

Additional prospective studies with larger sample sizes are needed to confirm the robust reproducibility and generalizability of our findings. Visualizing and retrospectively quantifying the association of life exposures, stress-associated neuroendocrine factors, and HPPs may thus contribute to elucidating the mechanisms responsible for the embedding of stress and other life exposures in human biology. All data generated and analyzed during this study are included in the supporting data files.

Source data files have been provided for Figures 1, 2, 3, and 4, and for figure supplements Figure 1—figure supplement 4, Figure 1—figure supplement 5, Figure 2—figure supplement 1, Figure 3—figure supplement 2, Figure 4—figure supplement 1, Figure 5—figure supplement 2.

Our editorial process produces two outputs: i public reviews designed to be posted alongside the preprint for the benefit of readers; ii feedback on the manuscript for the authors, including requests for revisions, shown below. We also include an acceptance summary that explains what the editors found interesting or important about the work.

This is an interesting and informative study reporting on the molecular features of reversible hair greying in humans and the connection with psychological stress. This work will set the stage for future mechanistic studies and represents an important conceptual and methodological advance. Your article has been reviewed by 3 peer reviewers, including Matt Kaeberlein as the Senior and Reviewing Editor and Reviewer 1.

The following individual involved in review of your submission has agreed to reveal their identity: Michael P Philpott Reviewer 2.

The reviewers have discussed their reviews with one another, and the Reviewing Editor has drafted this to help you prepare a revised submission. The interpretation of the reported -omics changes remains somewhat superficial. A more in-depth discussion of the pathways found changed in the greying process would be appreciated. The data suggest changes in fatty acid metabolism with loss of pigmentation.

Changes in fatty acid metabolism are associated with senescence. Did the authors detect any markers of senescence in their study? This is an interesting and informative study reporting on the molecular features of reversible hair graying in humans and the connection with psychological stress. The study appears to have been very well conducted and the interpretations are generally supported by the data. While the results are primarily correlative at this stage, this work will set the stage for future more mechanistic studies and represents an important conceptual and methodological advance.

Further the data suggest changes in fatty acid metabolism with loss of pigmentation. Did the authors detect any markers of senescence in their study.

The only weakness of the manuscript is that the interpretation of the reported omics changes remains somewhat superficial. Of course, it would also be of interest to see a higher N in a number of the presented assays, however, the presented data appears to suffice the character of a pilot study aiming at the establishment of a new method by providing a very detailed analysis of individuals samples.

Thank you for this suggestion to help strengthen the discussion of our results. We focused our discussion on the most robust and unambiguous results, which are somewhat limited given the challenge to extract and detect a fair number of protein from the resistant hair matrix. We have expanded our discussion of the greying pathways in the discussion:.

Excellent question. We agree that it would be valuable to detect stress hormones in parallel with the hair pigmentation pattern and proteomic changes at the single-hair level. To our knowledge, current methods require multiple milligrams of hair for analysis Sauve, Koren, Walsh, Tokmakejian, and Van Uum, and are only done on bulk hair material, rather than on single hairs.

Therefore, it was not possible given existing technology to capture this kind of data longitudinally along single hairs. We did not detect any canonical markers of senescence in our proteomic results. However, although not a direct marker of senescence, previous work has showed that HF aging is associated with a marked decline in 2 hair keratins and 7 keratin-associate proteins KAPs Giesen et al.

We now briefly mention these findings in the manuscript, but the downregulation for some of these proteins was not very robust, as we previously mentioned in the manuscript p. Our data comparing white to dark hairs showed that 14 of the reported upregulated proteins were also upregulated in the white hairs in our second proteomic experiment. We have added a column to Supplementary file 2 to indicate which of the proteins that we detected were also found to be upregulated in the older hairs in the Plott et al.

In our view, these findings should be regarded as converging but not definitive evidence, and additional studies in both hair shafts and follicles are needed, using canonical markers of senescence. Thank you for a thoughtful review. As discussed above, there are currently no available method to examine stress hormones at this resolution see above response to Essential Revisions 2 — but this would be a terrific addition for future experiments.

We have now integrated this important suggestion into the closing statement of the revised Discussion p. Excellent point. As explained above see above response to Essential Revisions 3 , the observed changes in protein abundance related to fatty acid metabolism FASN, CPT1a are entirely consistent with a pro-senescence state.

However, our proteomics results did not contain any canonical senescence marker. We now discuss this in detail on p. Thank you for this recommendation. In addition, we clearly acknowledge in the revised Discussion that a higher n of investigated individuals and hair shafts, namely in the proteomics and hair pigmentation profiling, is needed to confirm robust reproducibility of our findings p.

Fafian-Labora, J. O'Loghlen, A. FASN activity is important for the initial stages of the induction of senescence. Cell Death Dis, 10 4 , Flores, A. Lowry, W. Lactate dehydrogenase activity drives hair follicle stem cell activation. Nat Cell Biol, 19 9 , Giesen, M. Ageing processes influence keratin and KAP expression in human hair follicles.

Exp Dermatol, 20 9 , Mancino, G. Dentice, M. When diet and vitamin deficiencies are the cause of prematurely white hair, correcting these may reverse the problem or stop it from worsening.

A diet rich in antioxidants can reduce oxidative stress. Anyone who has white hair resulting from a vitamin deficiency should consume more foods loaded with those vitamins. For example, seafood, eggs, and meats are good sources of vitamin B, and milk, salmon, and cheese are excellent sources of vitamin D. Smoking has adverse effects on the body and contributes to white hair. And researchers have found a link between the habit and loss of hair pigmentation.

There are plenty of hair dyes on the market that cover white hair, but many of these contribute to premature graying and may cause allergic and adverse reactions. Natural remedies offer an alternative to slow down hair-whitening without harming the body or causing further hair pigment damage. Curry leaves. The medicinal use of curry leaves goes back centuries. When combined with hair oil and applied to the scalp, curry leaves can slow premature graying.

One report in the International Journal of PharmTech Research highlights the traditional use of curry leaves to retain black hair color and even prevent premature graying. Curry leaves can be purchased at Indian supermarkets, as well as traditional grocery stores. The false daisy or bhringaraj will darken hair and keep it from becoming white early, according to some reports.

The juice of the leaves is boiled in coconut oil or sesame oil and massaged into the hair. Indian gooseberry. Also called amla, this is an herbal supplement recognized for reversing premature graying by promoting pigmentation. Its effectiveness is believed to be because the gooseberry is rich in antioxidants and anti-aging properties.

Amla is available as a fruit in Indian grocery stores. It can also be found, as a powder or supplement, available online or in a traditional health food stores. The powder can be mixed with coconut oil and applied directly to the scalp. Black tea. Black tea can make hair darker, shinier and softer. It can be used by steeping 3 to 5 tea bags in 2 cups of boiling water , cooling and adding to clean, wet hair. Tea can also be mixed with conditioner, left in the hair for 1 hour, and then rinsed out.

Rather than stress about your stress levels, concentrate on the external factors that cause gray hair but are still within your control. Hayag lists nutritional deficiencies including vitamin B12, folate, copper, iron, and calcium as causes, as well as smoking, since it adds to aforementioned oxidative stress, and a sugar-rich diet. Hayag has an answer for that, too. Leave those silver hairs right where you found them. From this point, you have two options: Do you want to completely cover your gray strands, or let nature take its course?

If you vote for the latter, eSalon Hair Colorist Leianna Hillo offers three solutions for blending while you gray: demi-permanent hair color, highlights, or a combining both approaches. Highlights can blend in with grays and make the grow-out phase a little easier.

After a few applications, your regrowth will be less and less noticeable. Adding pigment also increases moisture in hair, which is why a semi-permanent color will usually leave your hair feeling nourished and hydrated.