Antiaging skincare products are beginning to try and increase autophagy to rejuvenate skin.
Increasing skin autophagy, especially of mitochondria, is a new way to slow skin aging. Many new ingredients are being developed for skin care products to reverse skin aging by increasing autophagy.
Autophagy[iii] is the process of cell ‘eating themselves”.[iv] In other words, cells break down old organelles and recycle them. Autophagy serves the purpose of eliminating senescent cells, damaged organelles, proteins, and pathogens, as well as regulating apoptosis (programmed cell death), cell differentiation, immunity, and inflammation.
Are ingredients that increase autophagy right for your skin?
The best skincare depends upon what your Baumann Skin Type® is. Our advice is to take the skin care quiz, find out your skin type, and our dermatologists will give you specific skin care routine recommendations. These may include skin care ingredients that increase autophagy.
Antiaging Skin Care Ingredients That Increase Autophagy
Ingredients in cosmeceutical skin care products that promote autophagy are:
· Aquatide™ same as Heptasodium hexacarboxymethyl dipeptide-12
· Heptasodium hexacarboxymethyl dipeptide-12
The Science Of Autophagy
The science of aging skin is well understood. Autophagy has been newly discovered as an important part of the aging process. Autophagy is the process by which lysosomes fuse with a cellular organelle and digest it. This recycles the cellular components.
Autophagy regulates extracellular matrix (ECM) metabolism by affecting matrix metalloproteinases (MMPs). Blocking autophagy leads to an increase in MMPs and an increase in collagen breakdown. TGF-β is a growth factor involved in the regulation of autophagy.[vii]
Autophagy has a circadian rhythm[viii].
How To Increase Autophagy With Caloric Restriction And Intermittent Fasting
Autophagy is induced by nutrient starvation, oxidative stress, infection, and two protein kinases (unc-51 like kinase complex and the phosphatidylinositol 3-kinase complex).[ix] We are still learning how to increase autophagy but the most proven way is with intermittent fasting and caloric restriction. Upregulation of autophagy is thought to contribute to the prolongation of lifespan seen with caloric restriction.
Mitochondria and Autophagy
The ability for mitochondria to generate autophagy is particularly important in preventing aging because old mitochondria cause damaging free radicals. Increasing autophagy, especially in mitochondria, is an anti-aging strategy. Increasing autophagy delays aging in flies, worms, and mice.[x] Substances that induce autophagy such as lithium and trehalose have been shown in nematodes and mice to improve mitochondrial function, reduce senescence, and expand the lifespan.
Sirtuins and Autophagy
Sirtuin-1 (SIRT-1) has been shown to be the reason that caloric restriction improves health and longevity. Activation of SIRT-1 induces autophagy[xi].
Autophagy and Skin
Autophagy is seen in both proliferating and differentiating keratinocytes. It helps maintain skin stem cells by promoting the removal of oxidized molecules, improves nucleotide excision repair,[xii] and removes lipofuscin.[xiii] Old human dermal fibroblasts have significantly less autophagy than those of young dermal fibroblasts. Loss of autophagy leads to the induction of cellular senescence. Cellular senescence leads to skin aging.
[i] Jeong, D., Qomaladewi, N. P., Lee, J., Park, S. H., & Cho, J. Y. (2020). The Role of Autophagy in Skin Fibroblasts, Keratinocytes, Melanocytes, and Epidermal Stem Cells. Journal of Investigative Dermatology, 140(9), 1691-1697.
[ii] Baumann L. Intrinsic Aging in Baumann’s Cosmetic Dermatology 3rd edition (McGraw Hill 2022)
[iii] Levine, B., and Kroemer, G. (2019). Biological functions of autophagy genes: a disease perspective. Cell 176, 11–42.
[iv] Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451(7182):1069-75.
[v] Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaras K, et al. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis. 2010;1(1):e10.
[vi] Lee, J. H., Moon, J. H., Nazim, U. M., Lee, Y. J., Seol, J. W., Eo, S. K., ... & Park, S. Y. (2016). Melatonin protects skin keratinocyte from hydrogen peroxide-mediated cell death via the SIRT1 pathway. Oncotarget, 7(11), 12075.
[vii] Jeong, D., Qomaladewi, N. P., Lee, J., Park, S. H., & Cho, J. Y. (2020). The Role of Autophagy in Skin Fibroblasts, Keratinocytes, Melanocytes, and Epidermal Stem Cells. Journal of Investigative Dermatology, 140(9), 1691-1697.
[viii] Solanas, G., Peixoto, F. O., Perdiguero, E., Jardí, M., Ruiz-Bonilla, V., Datta, D., et al. (2017). Aged stem cells reprogram their daily rhythmic functions to adapt to stress. Cell 170, 678–692.
[ix] Lim, C. J., Lee, Y. M., Kang, S. G., Lim, H. W., Shin, K. O., Jeong, S. K., ... & Park, B. D. (2017). Aquatide activation of SIRT1 reduces cellular senescence through a SIRT1-FOXO1-autophagy axis. Biomolecules & therapeutics, 25(5), 511.
[x] Park, J. T., Lee, Y. S., Cho, K. A., & Park, S. C. (2018). Adjustment of the lysosomal-mitochondrial axis for control of cellular senescence. Ageing Research Reviews, 47, 176-182.
[xi] Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaras K, et al. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis. 2010;1(1):e10.
[xii] Qiang, L., Zhao, B., Shah, P., Sample, A., Yang, S., and He, Y. Y. (2016). Autophagy positively regulates DNA damage recognition by nucleotide excision repair. Autophagy 12, 357–368
[xiii] Höhn, A., Sittig, A., Jung, T., Grimm, S., and Grune, T. (2012). Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts. Free Radic. Biol. Med. 53, 1760–1769