The Reversible Silver Fox: Grey Hair Can Regain Pigmentation

Hair greying is a hallmark of aging generally believed to be irreversible and linked to genetics and stress. But this relationship, along with reversal of greying, remain insufficiently understood. This paucity is mostly due to the lack of sensitive methods to precisely correlate stressful processes with hair pigmentation and greying events at the level of individual follicles.

Now, by developing an approach to profile hair pigmentation patterns along individual human hair shafts, Rosenberg and colleagues from Columbia University find grey hairs that naturally regain pigmentation across sex, ethnicities, ages, and body regions, defining the reversibility of greying in humans. Published in the journal eLife, this new method to quantitatively map recent life history in hair pigmentation patterns provides an opportunity to examine the influence of stress on human aging.

“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” says the study’s senior author Martin Picard, PhD, associate professor of behavioral medicine at Columbia University Vagelos College of Physicians and Surgeons. “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.”

What Causes Hair to Grey?

The color in pigmented hair is provided by granules called melanin that continuously are supplied to the growing hair shaft by cells called melanocytes in a structure called the hair follicle pigmentation unit (HFPU). Age-related greying is thought to involve the exhaustion of stem cells that generate these hair-coloring melanocytes. 

Although hair greying is generally considered a progressive and irreversible age-related process, cases of drug- and mineral deficiency-induced depigmentation or repigmentation of hair have been reported, reflecting the influence of environmental inputs into HFPU function. Because most hairs are continually growing from a living hair follicle, which is sensitive to changing conditions, into a hardened hair shaft external to the body that retains stable molecular traces of these conditions, the hair shaft represents a living archive of recent exposures, from chemicals to social experiences.

“Just as the rings in a tree trunk hold information about past decades in the life of a tree, our hair contains information about our biological history,” Picard says. “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. Once hairs grow out of the scalp, they harden and permanently crystallize these exposures into a stable form.”

High Resolution Images Show Hair Doesn’t Grey Continuously

Here, Rosenberg and colleagues describe a new approach based on high resolution imaging to map hair pigmentation patterns in single hairs undergoing greying and reversal transitions. To examine hair pigmentation patterns in human hairs, the Columbia University researchers plucked, imaged, digitized, and analyzed hundreds of hairs from 14 healthy donors.

Three main pigmentation patterns initially emerged from this analysis: dark, white, and initially dark hairs that undergo a sharp greying transition from dark to white over a single hair follicle growth cycle.  This approach to quantify hair pigmentation patterns 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.

Though the scientific literature generally assumes pigment production in the HFPU to be a continuous process, here Rosenberg and colleagues document a complete switch-on/off phenomena during a single cycle of hair growth. “If you use your eyes to look at a hair, it will seem like it’s the same color throughout unless there is a major transition,” Picard says. “Under a high-resolution scanner, you see small, subtle variations in color, and that’s what we’re measuring.”

The Hair-Greying Threshold

In addition to high magnification imaging, Rosenberg and colleagues performed experiments quantifying the population of proteins, also known as the proteome, in greying human hairs. A notable finding from these protein profiling experiments is the bias toward upregulation rather than the loss of proteins in depigmented grey hair. Molecularly, grey hairs upregulate proteins related to energy metabolism, mitochondria, and antioxidant defenses.

To generalize these observations, the Columbia University researchers developed a computational simulation, which suggests a threshold-based mechanism for the temporary reversibility of greying. 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.

“We think hair needs to reach a threshold before it turns gray,” Picard says. “In middle age, when the hair is near that threshold because of biological age and other factors, stress will push it over the threshold and it transitions to gray. But we don’t think that reducing stress in a 70-year-old who’s been gray for years will darken their hair or increasing stress in a 10-year-old will be enough to tip their hair over the gray threshold.”

Stress Influences Hair Pigmentation Loss and Gains  

The resolution of this new hair pigmentation patterns profiling approach provides investigators with an instructive new research tool that allows us to link, with an unprecedented level of resolution, hair greying/reversal events with psychosocial exposures. Combining hair pigmentation patterns and proteomics on single hairs, Rosenberg and colleagues also report hair greying and reversal that can occur in parallel with psychological stressors.

Rosenberg and colleagues provided proof-of-concept evidence that biobehavioral factors are linked to human hair greying dynamics. “There was one individual who went on vacation, and five hairs on that person’s head reverted back to dark during the vacation, synchronized in time,” Picard says. This hair pigmentation pattern 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.

References:

Rosenberg AM, Rausser S, Ren J, et al. Quantitative mapping of human hair greying and reversal in relation to life stress. Elife. 2021;10:e67437. Published 2021 Jun 22. doi:10.7554/eLife.67437