Is it possible to reverse gray hair




















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We know it's a hassle to switch browsers but we want your experience with CNA to be fast, secure and the best it can possibly be. To continue, upgrade to a supported browser or, for the finest experience, download the mobile app. CNA Lifestyle Stress, smoking and bad diets equals grey hair — can you still reverse the process? Lorraine Robert. Bookmark Bookmark Share. Keeping a healthy lifestyle and lowering stress levels may get you your dark locks back.

However, according to a recent study, there is a way to restore hair color to graying tresses that doesn't involve a trip to the hair salon—although it may not work for everyone. The study, published in eLife , found that stress-induced hair graying can be restored if the stress is eliminated, according to researchers at Columbia University Vagelos College of Physicians and Surgeons.

The study's senior author Martin Picard, Ph. Our data add 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," Picard said in a press release.

When hairs are still under the skin as follicles, they are subject to the influence of stress hormones and other things happening in our mind and body.

The rate at which HS regain pigmentation during reversal was 0. Thus, rather than drifting back toward the original color, repigmentation of white human HS occurs within the same time frame and at least as rapidly as the process of greying itself. The spectrum of greying transitions and reversals patterns observed in our cohort, including measured rates of repigmentation along individual hairs, is shown in Figure 2—figure supplement 1.

The HPP results establish the wide range of naturally occurring rates of pigmentary changes in single hairs, which vary by up to an order of magnitude from hair to hair. We then asked whether the reversal of greying is governed by a process that is unique to each human scalp HF or if it is likely coordinated by systemic factors that simultaneously affect multiple HFs.

In our combined cohort, three individuals had multiple two-colored hairs collected at either one or two collection times within a one-month interval. In each case, the multiple two-colored hairs originated from independent HFs separated by at least several centimeters e. If the hairs are independent from each other, the null hypothesis is that different HSs will exhibit either greying or reversal changes at different positions along each hair, and will have independent HPPs.

If multiple HSs were coordinated by some systemic factor, then we expect HPPs to exhibit similarities. In a first year-old female participant with dark brown hair, three two-colored hairs were identified at a single instance of collection.

Notably, all three hairs exhibited dark-to-white greying. In A and B, simultaneously plucked dark and white hairs are plotted for reference. D HS from a year-old Asian female with 2 months of self-reported profound perceived stress associated with temporary hair greying and reversal. Note the synchronicity between the increase in stress and rapid depigmentation i.

Numbers 1 to 6 correspond to HS segments on D. H Trajectories of protein abundance from the top Component one and I Component two features across the six segments; proteins with positive top and negative loadings bottom are shown separately.

In a year-old female participant with brown hair, two transition hairs were identified. Thus, these findings extend previous reports in single isolated hairs by providing quantitative accounts of coordinated HS re pigmentation across multiple hairs. Candidate humoral hair pigmentation modulators that could create synchrony in greying or repigmenting hairs include neuropeptides, redox balance, and steroid or catecholamine hormones Hardman et al.

These factors must act in parallel with genetic factors that influence inter-individual differences in aging trajectories. Anecdotal case reports and a recent pilot study suggest that psychological stress and other behavioral factors accelerate the hair greying process Nahm et al.

However, contrary to mice where this process appears to be irreversible at the single hair follicle level, our data demonstrates that human hair greying is, at least under some circumstances, reversible.

This dichotomy highlights a potential fundamental difference between rodent and human HF biology, calling for a quantitative examination of this process in humans.

As evidence that environmental or behavioral factors influence human hair greying, epidemiological data suggests that smoking and greater perceived life stress, among other factors, are associated with premature greying Akin Belli et al.

Chronic psychosocial stress also precipitates telomere shortening, DNA methylation-based epigenetic age, as well as other biological age indicators in humans Epel et al.

In relation to mitochondrial recalibrations, psychosocial factors and induced stress can also influence mitochondrial energetics within days in humans Picard et al.

To generate proof-of-concept evidence and test the hypothesis that psychosocial or behavioral factors may influence greying at the single-HF level, we leveraged the fact that HPPs reflect longitudinal records of growth over time — similar to tree rings — which can be aligned with assessments of life stress exposures over the past year. By converting units of hair length into time, perceived stress levels can be quantitatively mapped onto HPPs in both greying and transitional hairs.

A systematic survey of two-colored hairs on the scalp of a year-old Caucasian male with auburn hair color over a 2-day period yielded five two-colored HS from the frontal and temporal scalp regions. Again, two-colored hairs could either exhibit depigmentation or reversal. Unexpectedly, all HS exhibited reversal. HPP analysis further showed that all HS underwent reversal of greying around the same time period.

We therefore hypothesized that the onset of the reversal would coincide with a decrease in perceived life stress. A retrospective assessment of psychosocial stress levels using a time-anchored visual analog scale participants rate and link specific life events with start and end dates, see Materials and methods and Figure 3—figure supplement 1 for details was then compared to the HPPs. The reversal of greying for all hairs coincided closely with the decline in stress and a 1-month period of lowest stress over the past year 0 on a scale of 0—10 following a 2-week vacation Figure 3C.

We were also able to examine a two-colored hair characterized by an unusual pattern of complete HS greying followed by rapid and complete reversal same as in Figure 2B plucked from the scalp of a year-old Asian female participant with black hair. HPP analysis of this HS showed a white segment representing approximately 2 cm.

We therefore hypothesized that this reversible greying event would coincide with a temporary increase in life stress over the corresponding period. Strikingly, the quantitative life stress assessment over the last year revealed a specific 2-month period associated with an objective life stressor marital conflict and separation, concluded with relocation where the participant rated her perceived stress as the highest 9—10 out of 10 over the past year.

The increase in stress corresponded in time with the complete but reversible hair greying Figure 3D. Given the low statistical probability that these events are related by chance, life stress is the likely preceding cause of these HS greying and reversal dynamics. These data demonstrate how the HPP-stress mapping approach allows to examine the coordinated behavior of greying and reversal dynamics with psychosocial factors, raising the possibility that systemic biobehavioral factors may influence multiple HFs simultaneously and regulate HPPs among sensitive hairs.

To assess whether rapid greying and reversal events among a single hair are molecularly similar or distinct to those described in the two proteomics experiments above, we dissected six segments two dark, two white, two reverted of the single HS in Figure 3D and quantified their proteomes as part of Experiment 2.

To examine how the proteome as a whole is altered through the greying and reversal transitions associated with psychosocial stress levels, we generated a PLS-DA model with all six segments. Both dark segments clustered together, with similar values on both first and second principal components. The white and reverted segments clustered in separate topological spaces Figure 3F. Greying was associated with a positive shift largely along the first component Component 1 , whereas reversal was associated with a negative shift on the second component Component 2 and a more modest negative shift in Component 1.

In contrast, a null set of hair proteins not contributing to either components exhibited enrichment for extracellular exosomes and cell-cell adhesion that reflect hair shaft biology Figure 3—figure supplement 2 , illustrating the specificity of our findings related to greying and reversal. These data indicate that the reversal of greying at the single-hair level is not associated with a complete reversal in the molecular composition of the HS.

Rather, some of the proteomic changes in hair greying are enduring despite successful repigmentation. B Venn diagram illustrating the intersection of datasets. The number of overlapping proteins across datasets that are either consistently down- or upregulated, or proteins not regulated in the same direction, are shown for each area of overlap. Fold difference values are the mean fold differences relative to dark hairs. E Summary of significantly enriched KEGG categories across datasets, for upregulated left and downregulated right proteins.

Four main clusters are highlighted and labeled by their top KEGG category. To systematically examine the overlap among the different proteomic datasets and to derive functional insight into the hair greying process in humans, we then integrated results from the three datasets described above.

White HS show consistently more upregulated than downregulated proteins across datasets 2. This preferential upregulation suggests that the depigmentation process likely involves active metabolic remodeling rather than a passive loss of some pigmentation-related factor. The overlap in the specific proteins identified across dark-white comparisons and among the 6-segments hair is illustrated in Figure 4B.

Five proteins were consistently upregulated between experiments 1 and 2. These include three well-defined resident mitochondrial proteins involved in lipid metabolism: CPT1A, which imports fatty acids into mitochondria Schlaepfer and Joshi, ; ACOT7, which hydrolyzes long-chain fatty acyl-CoA esters in the mitochondrial matrix and cytoplasm Bekeova et al.

The other two proteins include the actin-depolymerizing protein cofilin-1 CFL1 and the core glycolysis enzyme phosphoglycerate kinase 1 PGK1 Figure 4C.

Interestingly, beyond its role in cytoskeleton dynamics, CFL1 promotes mitochondrial apoptotic signaling via cytochrome c release Hoffmann et al. And although PGK1 is a cytoplasmic kinase, it was recently demonstrated to translocate inside mitochondria where it phosphorylates and inhibits pyruvate dehydrogenase and Krebs cycle activity Nie et al.

Thus, all five proteins validated across both experiments are linked to mitochondrial energy metabolism, implicating mitochondrial remodeling as a feature of hair greying. Interestingly, all five proteins have also been linked to the biology of melanocytes Bracalente et al. The downregulated proteins were keratins, with small effect sizes, and not particularly robust.

Analysis of the intensity based on absolute quantification iBAQ data confirmed the upregulation of these five mitochondrial proteins, and the absence of substantial changes in the keratins. Together, these data suggest that HS proteome profiling may provide a retrospective access to some aspect of melanocyte metabolism, which opens new possibilities to study HF aging biology. 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.



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