Hair roots sniff sandalwood
(appeared in Sep 2018)

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Hair roots may share a sense of smell with the outer layer of the skin, says S.Ananthanarayanan.

The skin is the largest organ in the body. Adults have about 3.5 kilograms of skin, and 20 square feet of it. Skin is the body’s waterproof cover, an insulator that guards the body against extreme heat and cold, against water loss, against the harmful part of sunlight and against damage by chemicals. It produces antibacterial substances that save us from infection and it generates Vitamin D, which enables absorption of calcium for healthy bones

It is also the body’s communication centre. The skin has nerve tissue that tell the brain about the environment – hot and cold and a sense of touch that can make out shapes and surfaces, with such sensitivity that it all but replaces the sense of sight in the sightless. The nerve endings on the tongue and the in the nose also detect and convey information about chemicals in the environment. And then, skin is flexible, for it can bend and stretch, and it repairs itself if it is damaged.

Jérémy Chéret, Marta Bertolini, Leslie Ponce, Janin Lehmann, Teresa Tsai, Majid Alam, Hanns Hatt and Ralf Paus, from industry and the university at Münster, Germany, Ruhr-University and Universities of Manchester and Miami write in the journal, Nature Communications about the multiple roles of the hair that grows on skin. While hair, which is present in all parts of the skin, protects skin and helps sense touch or movement, it is also a powerful initiator of healing when skin injured. And a further finding that the group reports is that the olfactory faculty, or the capacity to detect chemicals in the air, is not confined to the nose, it appears to be there over most of the skin too. But a remarkable discovery the group reports is that a synthetic sandalwood odorant (sadly, not the natural sandalwood) promotes the action of hair follicles both in wound healing and in promoting the growth of hair!

Dr Bishop reported that fresh skin begins to grow around the remaining hair follicles and the edge of the damaged skin. And scar tissue forms only if the injury is so deep in the dermis (see picture), the inner layer of, that the base of the hair follicles are destroyed. A clear demonstration of the utility of hair follicles in wound healing is the fact that wounds in areas that abound in hair follicles, like the scalp, heal rapidly. Wounds in areas that lack hair follicles, like the palm of the hands, take longer to heal. When skin grafts are done, it is known that the healing time is 5-6 days if the source of the graft was the scalp, against 10-14 days if the source was the thighs or the abdomen.

But coming back to detection of chemicals, it is on record that humans can distinguish over a trillion different odors. The Nature Communications paper, however, says that ‘olfactory reception’ is a chemosensory signaling system of great evolutionary antiquity, which predates the development of smell sensation. Olfactory receptors, the cellular structures that sense chemicals are hence not restricted to the nose but are present in other tissue as well. Non-smell roles of these receptors in such tissue have also been studied, the paper says.

Several of these receptors, called ‘ORs’, are also there in the outer layers skin tissue, the papers says. Among them is OR2AT4, which, when activated, promotes the migration of cells that produce keratin, the material of the skin. This OR has been now been found to be expressed by the hair follicles. It is otherwise well known that the hair follicle is reservoir of stems cells, which are cells that can differentiate into other types of cells. Stem play their greatest role in the developing embryo for the formation of different organs. They are, however, needed throughout life, for normal regeneration of tissue and for repair. The recorded effect of the presence of hair follicles in promoting wound healing is hence apparently as a result of stem cells playing a role.

What the Nature Communications paper points out is that a commercial, synthetic preparation, Sandalore®, which has an odor similar to sandalwood, has been found to promote the activity of the olfactory receptor, OR2AT4. Faster migration of skin cells has been observed in the lab, and better progress of actual healing of wounds, the paper says. That OR2AT4 is the substance involved has been confirmed by adding Phenirat®, a known antagonist of OR2AT4. Sandalore®, induced activity in Cells with OR2AT4 was to be blocked by Phenirat®. Conversely, when OR2AT4 suppressed, it was seen that Sandalore® did not have the

Given the association of the presence of hair follicles with wound healing, the authors of the paper surmised that OR2AT4 may also impact hair growth. It was then seen that activation of OR2AT4 by Sandalore® prolongs the active growth phase of hair follicles, during which the root of the hair is dividing rapidly, adding about one centimetre to the hair shaft every twenty eight days. This action appears to arise by decreasing the pace of death cells that create keratin, through increasing the production of a growth stimulating hormone in the outer root sheath. Conversely, when OR2AT4 was suppressed, it was seen that Sandalore® did not have the growth promoting effect, which shows that the effect of Sandalore® is specific to OR2AT4.

The conclusion of the exercise, the paper says, is that “hair follicles are able to “smell” in the sense that they recruit the evolutionarily oldest and largest of all receptor families (the olfactory system) for regulating key organ functions”. The study, in any case, holds out a tantalizing hope that Sandalore®, a preparation that is used perfumes, moisturizers and cleansing agents, could find application to help hair growth!

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