Senescence, autophagy and skin aging

Senescence is defined as a progressive loss of body functions. According to Prof. Gérald E. Pierard from the University of Liège "skin senescence which is the global reflection of the influence of many intrinsic and extrinsic factors can be divided into seven types (chronological, actinic, genetic, endocrine, catabolic, addictive and gravitational)." Senescent cells accumulate in the skin, but the whole body is affected.

For her part, Prof. Judith Campisi of the Buck Institute for Research on Aging paid some attention to the question of knowing when and where senescence begins and what were the associated mechanisms. "It is a very complex process, which can be partly explained by the secretion from senescent cells of numerous pro-inflammatory cytokines, growth factors and proteases which have been called SASP (Senescence Associated Secretory Phenotype)" she explained.

Skin models consisting of fibroblasts, keratinocytes or melanocytes are also widely used to study aging. Thus the Dr. Martine French from the Laboratory of Hematology, Hospices Civils de Lyon, demonstrated that in senescent fibroblasts, the size and number of autophagy vacuoles increase in comparison to young fibroblasts. For keratinocytes, the level of autophagic activity that determines cell death and for melanocytes, their decreased activity with age leads to skin pigmentation defects and to a loss of efficiency of the tissue homeostasis. "After 30 years of age, there is loss of 8 to 10% of the melanocyte activity per decades hence the appearance of white hair, senile lentigo and of hypomelanosis" explains Corinne Bertolotto, from the Inserm U1065 in Nice.

Finally, aging can also be observed at the mitochondria level (Dr. Carine Nizard, LVMH Recherche) or at the level of the extracellular matrix whose structure alters with age (Dr. Sylvie Brassart-Pasco, CNRS - Laboratory of Medical Biochemistry and Molecular Biology).

Delay or counter aging?

In this context, what are the pathways leading to an "optimal" aging or even to the reversibility of the process? One of the avenues investigated by Dr. Jean-Marc Lemaître, Institute of Functional Genomics of Montpellier, is that of stem cells. "Recently we were able to develop a screen to identify the target genes capable of influencing the entry into senescence or its avoidance using a specific combination of six reprogramming factors, we were able to reprogram senescent cells of aged donors." In these experiments, signs of aging, such as those associated with the telomere length, the loss of mitochondria efficiency, were eventually faded out.

At the skin level, it is already possible to achieve rejuvenated fibroblasts or keratinocytes. We all noticed that from one individual to another, longevity is different and depends, according to Lemaitre, "of genetic and epigenetic factors for respectively 25% and 75%." Lifestyle, diet, stress have an influence on molecular decline.

Varied assessment methods

To evaluate the aging of organisms, some address senescence from the angle of the regulation of gene expression. This is in particular the case with the Prediguard Company. "We study the genes of young and aged skin and make correlations between the differences observed and the pathologies developed "explains Dr. Philippe Benech founder and Head of Prediguard.

Others will focus on skin constituents taken separately or as a whole. Thus, the Bioexigence Company studied the contractile properties of aged fibroblasts at the bottom of wrinkles. "Fibroblasts inside wrinkles develop less contractile forces than fibroblasts from surrounding unwrinkled aged skin" explains Dr. Carol Corderot-Masuyer, Manager.

The Straticell Company has studied premature senescence induced by free radical stress or by UVBs. But measurements assessing the colour and consistency of the complexion are also performed by Skinexigence, demonstrating that this criterion has an influence when determining the perceived age. Because finally, isn’t the main goal to look younger than one’s actual age? The Chanel company has on this topic, shared a consistent study performed on 289 women aged from 20 to 70 and demonstrating that colour contrasts observed at the face level are a good marker of perceived age. Hence, couldn’t simply applying make-up be enough to create an illusion of youth?

Concerning actives...

This solution is not exclusive and suppliers of cosmetic actives are working on their side to offer always more efficient molecules.

This year, the ends of chromosomes - the telomeres for which research work was awarded a Nobel Prize in 2009 - are the target of new substances that are found under the name of Juvinity at Sederma, Telosomyl at Silab and Telosense at Ashland ISP.

For Biotechmarine and Lucas Meyer Cosmetics, progerin is the new marker that their latest actives are targeting. Induchem-Libragen has worked on a new class of receptors, the DOR (Delta Opiod Receptors) which are involved in the control of the skin differentiation process. The anti-glycation activity of the Sakura extract of Oryza Oil and the detoxifying and plumping activities of Effipulp proposed by Expanscience were also highlighted.

This edition of the Jean-Paul Marty Days being completed, the French Society of Cosmetology is already preparing the next one on the theme: "Skin and photoprotection."