Paolo Giacomoni, PhD, Insight Analysis Consulting09.01.23
Far from being an academic curiosity, circadian (from the Latin circa diem, around the day) rhythms play relevant medical roles. Let us consider one example. The treatment of some cancers requires drugs that have the undesirable side effect to be toxic for the lymphocytes. The number of lymphocytes per unit volume in human blood changes according to a circadian rhythm. It is known that a drug, at a certain concentration, “kills” a certain fraction (a fraction, NOT a defined number) of target cells; so, if the drug is administered when the lymphocytes are present in larger number, the number of lymphocytes surviving the treatment will be larger, and the consequences of the drug toxicity will be more tolerable. In a comparative study of treatment of ovary cancers with cis-platinum and doxorubicin, the survival after five years of the patients who received chemotherapy at the time of the day corresponding to the lymphocyte maximum was 75%, whereas no patients survived more than three years when the drugs were administered at random times; i.e., without considering the circadian rhythm of the lymphocytes.1
The day-night cycle is likely to be the source of the circadian rhythms, but which is the molecular signal to the body? For healthy people it is known that a gland in the brain, the pineal gland, harbors the biochemical reactions producing melatonin. The pineal gland is located at the chiasma, the X-shaped structure formed at a point in the brain where the two optic nerves cross over each other. It is therefore a location where there is a lot of light, relatively speaking. The melatonin-producing enzymes are inhibited by daylight, so melatonin is produced only at night. Melatonin is known to embody the signal which tells the body to sleep.2 Melatonin also inhibits the transcription of the gene of 5-lipoxygenase (an enzyme acting at the first steps in a pro-inflammatory process),3 thus interrupting adventitious, self-maintained inflammatory reactions such as those that can be provoked by prolonged, intense physical activity. This property of melatonin might be the cause of the popular belief that a good night of sleep is the best medicine.
Skin Biorhythms
During the night when the individual sleeps, the heartbeat rate decreases, the body temperature decreases and the oxygen consumption decreases. As it is the case for other body organs, skin, too, has been studied in detail to learn whether some of its characteristics change according to circadian rhythms. Several interesting observations have been reported. Between 2 o’clock and 5 o’clock of the morning, the penetration of substances such as methyl-nicotinate and hexyl-nicotinate is faster and is slowest around noon.4 Transepidermal water loss is less between 8:00pm and midnight and is most between noon and 4pm, whereas the accumulation of sebum is maximum between noon and 4pm.5Some authors claimed that the skin temperature (measured on the forearm) is maximum during the night, in contrast with the well-established data indicating that core body temperature is maximum late in the afternoon and minimum just before dawn. A quick look to Figure 7 in reference 5 could allow one to say that, in the case of the temperature of the skin on the volar aspect of the arm, the existence of a biorhythm can be in the eye of the beholder!
Other aspects of skin physiology, such as cell replication, have been studied to learn about their circadian rhythms. The replication of skin cells has been studied by:
- Taking biopsies at different times of the day and of the night;
- Incubating the biopsies in a solution of radioactive Thimidine;
- Embedding in paraffin and slicing with microtome; and
- Performing autoradiography of the “slices.”
Conclusion
In human skin, several physiological parameters vary according to circadian rhythms and this might be of interest insofar as the preparation of products to be used at night is concerned. As a matter of fact, one could ask questions about the opportunity to add in a night cream, ingredients such as melatonin or boosters of DNA repair, squalene or ceramides, exfoliators or anti-pigmentogenic materials and so forth. One should be careful, though, when interpreting the data obtained with cultured cells (generally grown in the darkness of a CO2 incubator) and, before making decisions, make sure that they can be translated to the in vivo situation.References
- Hrushesky WJM, März WJ (1994) Chrono-chemotherapy of malignant tumors: Temporal aspects of antineoplastic drug toxicity. In: Biological Rhythms in clinical and laboratory medicine (Touitou and Haus editors) Springer Verlag pp 611-634
- The Aging Clock (1994) (Pierpaoli, Regelson, Fabris editors) The New York Academy of Sciences volume 719
- Steinhilber D et al (1995) The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes. J. Biol. Chem 270:7037-7040
- Reinberg et al (1995) Circadian dosing time dependency in the forearm skin penetration of methyl and hexyl nicotinate. Life Sc. 57:1507-1513
- Le Fur et al (2001) Analysis of circadian and ultradian rhythms of skin surface properties of face and forearm of healthy women. J. Invest. Dermatol. 117:718-724
- Schell H et al. (1975) Autoradiographic in vitro studies on diurnal variation in human epidermal cell proliferation. Arch Dermatol Res (1975) 257:265-272.
Paolo Giacomoni, PhD
Insight Analysis Consulting
paologiac@gmail.com
516-769-6904
Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as Executive Director of Research at Estée Lauder and was Head of the Department of Biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents. He is presently Head of R&D with L.RAPHAEL—The science of beauty—Geneva, Switzerland.