While it may seem intuitive that stress can increase the rate at which hair turns gray, a new study from researchers at Columbia University Vagelos College of Physicians and Surgeons is the first to offer quantitative evidence linking psychological stress to graying hair in humans and indicates hair color may be restored upon elimination of stressful life events. This new finding overturns an earlier study in mice that suggested that stressed-induced graying of hair is permanent.

The study, published in the eLife article, “Quantitative Mapping of Human Hair Greying and Reversal in Relation to Life Stress,” has broader significance than confirming the age-old speculation that stress grays hair, says the study’s senior author Martin Picard, PhD, associate professor of behavioral medicine in psychiatry and neurology at Columbia University Vagelos, College of Physicians and Surgeons.

“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 Picard. “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.”

A lack of sensitive protocols to precisely correlate periods of stress with hair pigmentation at the level of a single hair follicle, has until now prevented scientists from making a concrete causal connection between levels of mental stress and heightened graying.

Picard’s team has developed a new optical digitization method to map hair pigmentation patterns (HPPs) along individual human hair shafts, to produce timescales of phases when greying occurs rapidly. This novel approach uses HPP as a measurable readout of the ebb and flow of the aging process.

“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.”

Ayelet Rosenberg, first author on the study and a student in Picard’s laboratory, has developed a new method for capturing highly detailed images of tiny slices—about 1/20th of a millimeter wide—of human hairs to quantify the extent of graying. Each slice represents about an hour 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.”

In conjunction to analyzing individual hairs from 14 volunteers—7 males and 7 females of average age 35 years—the researchers also collected a retrospective stress assessment from two individuals-one male and one female-who showed discernible patterns of single-hair greying and reversal. The individuals were asked to review their calendars and rate each week’s level of stress 1–4 months after hair was collected from them.

The researchers observed some gray hairs naturally regain their original color. This had never been quantitatively documented, Picard says.

When Shannon Rausser, second author on the paper and a student in Picard’s laboratory, aligned hairs with stress assessments, the associations between stress and hair graying were striking. In some cases, the team observed a reversal of graying with the elimination of stress.

“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.

The team next performed mass spectrometry to measure levels of thousands of proteins in the hairs and how protein levels changed over the differently pigmented sections of each shaft of hair. Levels of 300 proteins changed with hair color, with a notable bias toward upregulation rather than the loss of proteins in depigmented hair segments. Their proteomics data supports other findings that show keratin-associated proteins are downregulated in white versus dark hairs.

The researchers then developed a mathematical model that suggests stress-induced changes in mitochondria may explain how stress turns hair gray. In contrast to a recent study on mice that showed a loss of stem cells in the hair follicle upon exposure to stress, the current study proposes a novel link between mitochondrial function and hair pigmentation. “We often hear that the mitochondria are the powerhouses of the cell, but that’s not the only role they play,” Picard says. “Mitochondria are actually like little antennas inside the cell that respond to a number of different signals, including psychological stress.”

“Our data show that graying is reversible in people, which implicates a different mechanism,” says co-author Ralf Paus, PhD, professor of dermatology at the University of Miami Miller School of Medicine. “Mice have very different hair follicle biology, and this may be an instance where findings in mice don’t translate well to people.”

A greying transition followed by complete reversal in a single hair shaft is imaged from bulb to tip. Pigmentation intensity was dynamically captured on a motorized stage microscope at ×10 magnification [Source: Columbia University Irving Medical Center/eLife]

“Based on our mathematical modeling, 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.”

To confirm the reproducibility and generalizability of these findings, prospective studies with larger sample sizes will be needed.

“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,” the authors conclude.