Formulators and dermatologists flocked to Orlando last month for the International Investigative Dermatology meeting. Estée Lauder scientists were invited to present their groundbreaking research, including findings on circadian rhythm, IR exposure and more.
 
 
According to Dr. Nadine Pernodet, VP-skin biology and bioactives research and development, Estée Lauder Companies and Estée Lauder brand lead scientist, the ELC R&D staff has been attending Society for Investigative Dermatology meetings for more than 20 years to discuss its latest scientific discoveries with other scientists and to receive feedback on that science from the scientific community. 
 
 
“We also get new ideas, a better understanding of skin biology, and we develop new collaborations with different universities and thought-leading dermatologists,” she added.
 
 
Pernodet presented findings on autophagy research, and its importance in skin cells regarding temporal changes and aging changes.


Autophagy is the body’s physiological process for cellular degradation and recycling. It is a critical player in the cellular aging process as well; increases in age have been associated with decreased autophagic activity, especially in the skin, according to Estée Lauder’s research.
 
 
Changes in the autophagic activity over time result in a decrease of energy supply and an increase of intracellular damages and oxidative stress, all of which would accelerate skin aging. This research addresses the impact of autophagy loss with age on skin cells as well as autophagic response to environmental stress induced by UVA.
 
 
Pernodet told Happi that natural actives are being developed to support and sustain natural autophagy activity over time to help to remove skin damage. For example, a yeast extract that was shown to help to regain natural autophagy activity in mature skin cells. 
 
 
“Over time, this will help skin cells to remove the accumulated damage necessary for health,” she said.
 
 
Another study looked at the impact of ozone pollution on skin, which the company notes is a growing environmental problem.
 
 
Ozone (O₃) pollution at ground level is a growing environmental problem. It is the result of increased air pollution, UV exposure and elevated temperatures. Ozone is known to create oxidative damage on lipids in the skin and is hypothesized to affect the main repair mechanisms of skin, such as circadian rhythm and autophagy. Using a custom-designed ozone chamber, environmentally relevant levels of ozone were shown to impact the core cellular machinery, resulting in a loss of repair and accumulation of damage in skin cells. Over time, this will accelerate visible skin aging, according to ELC.
 
 
“We followed reports around the world about ozone levels and mimicked these high ozone levels in a custom chamber we built in the lab,” explained Pernodet. “When we exposed skin cells in the ozone chamber, these levels were seen to be extremely damaging. We know that ozone is a very reactive molecule. What was surprising was just how fast the ozone damaged the cells.”
 
 
Circadian rhythm has been a focus of Estée Lauder’s research for years. At IID, the company unveiled new findings linking blue light exposure at night to a reduction in per-1 nighttime clock gene level in skin cells. Blue light exposure leads to an increase of free radical production, an increase of DNA damage, as well as an increased production of inflammatory mediators, indicating cellular damage due to skin cell desynchronization with their night rhythm. Results indicate that skin cells can “see” by sensing light directly through light-sensitive proteins called opsins, showing for the first time that skin cells control their own circadian rhythm, responding directly through a decrease of per-1 night clock gene. 
 

Pernodet noted that blue light is still essential to help skin synchronize with its daytime rhythm for higher protection. The much bigger damage that blue light creates is at night, when skin is “tricked” into thinking it is still daytime instead of getting the signal that it is time to enter their nighttime rhythm, she explained. 
 

“The result of this desynchronization is that skin cells are not entering the nighttime repair mode necessary for skin to naturally recover, and this is going to accelerate aging tremendously,” Pernodet told Happi.
 

In a paper entitled “Anti-Aging Effects of Retinoid Hydroxypinacolone Retinoate on Skin Models,” researchers noted that retinol is well known for its anti-aging effects on skin; however, issues such as skin irritation and photochemical instability are drawbacks of its use in cosmetic products. Therefore, it is of interest to identify new compounds that are retinol like, but are more stable, less irritating, and potentially more active.

 
According to Dr. Tom Mammone, VP-skin physiology and pharmacology, research and development, The Estée Lauder Companies, hydroxypinacolone retinoate (HPR), a cosmetic grade ester of ATRA, is unique in that it processes innate retinoic acid activity, and therefore does not need to undergo metabolic breakdown to achieve skin benefits. It has been demonstrated to be more stable and cause less skin irritation than ATRA. The results suggest that HPR is an effective cosmetic alternative to ATRA and other less effective retinoids in improving the appearance of aging skin without the irritation.

 
“HPR is very stable. That is the beauty of it,” explained Mammone. “Most retinoids are very unstable, so HPR represents an effective, more stable option that also causes less skin irritation.”

 
During IID, the Estée Lauder team also detailed its findings on how infrared radiation exposure leads to cellular senescence in reconstructed skin models. Prolonged exposure to ultraviolet radiation has deleterious effects on skin, however recent evidence suggests that premature skin aging is also influenced by infrared (IR) radiation. The IR spectra has distinct physiological effects based on wavelength and depth of skin penetration. In particular, IR-A radiation penetrates deep into the skin layers and induces oxidative stress, via the generation of reactive oxygen species. They hypothesized that oxidative damage from IR radiation causes cells to undergo cellular senescence, an irreversible form of cell cycle arrest. To address this, reconstructed skin models were irradiated with various doses of IR radiation.  Immunohistochemical analysis of the skins showed a dose dependent up-regulation of the senescence biomarkers b-galactosidase, p16INK4A, and p21CIP1, with increased exposure to IR radiation. This observed increase in expression in cell cycle inhibitors was corroborated by a decrease in the proliferation marker, Ki67. In addition, quantitative protein analysis of irradiated skins showed a significant increase in the expression of proteins associated with the senescence secretome, which includes IL-1a, IL-6, IL-8, VEGF-A, and MMP-1. These data suggest that IR radiation can lead to  cellular senescence, which is considered to be a contributing factor to biological aging.
 
 
“The mechanism by which IR induces senescence was speculative and was based on published data that suggests that IR causes oxidative damage,” explained Mammone. “We hypothesize that senescence is induced by the reactive oxygen species that are generated following IR radiation. We are currently performing further experiments to validate this hypothesis. If we prove that IR induced oxidative stress is the cause of cellular senescence then we can assess various antioxidants for protection.”
 

Finally, in the area of hair research, Aveda researchers detailed changes in the aging dermal hair follicle environment in female scalp. They noted that the hair follicle environment is central to an aged hair phenotype; as a result, the team examined the age-related changes in the scalp skin of women volunteers. The scalp tissue showed dramatic age-related changes, such as a loss of follicular multiplicity, decrease in hair follicle tissue depth, and other changes similar to skin, such as less pronounced rete-ridges. A number of changes that could potentially drive these findings were uncovered in research on scalp dermal fibroblasts such a reduction of collagen, versican, and hyaluronic acid synthase 2, which has implications for ECM structure and organization. These results demonstrate that hair aging is complex and multi-faceted.

 
“Our research is showing that, like facial skin, scalp skin similarly ages,” explained Dr. Alison Pawlus, senior research scientist, Estée Lauder Companies research and Aveda hair innovation and technology. “The difference is the scalp skin also needs to maintain large hair follicles that normally produce hair for approximately 7 years (terminal hairs).”

 
These hair follicles are embedded deeply into the scalp and require both structural support and a rich, constant supply of nutrients from the surrounding tissue.
 

“Our research collaboration with the University of Bradford, UK has uncovered substantial structural and biological changes which is leading to a better understanding of why the aged scalp skin does not support the hair follicle as effectively as young scalp,” said Pawlus.
 

Aveda’s new Invati Advanced line has multiple ingredients that help support the health of both the scalp and hair follicle, she added.

 
“These new discoveries will help us find new natural ingredients to specifically address age-related hair thinning to help our guests achieve their best hair possible.”