Why autophagy is essential for cells and cosmetics applications

Professor Yoshinori Ohsumi of Tokyo Institute of Technology, Japan, received the Nobel Prize in Physiology or Medicine in 2016, for his finding of essential genes relating to autophagy almost 30 years ago.

As awareness surrounding autophagy is now on the rise, we look at what it is, how it has come to the forefront of health care and what cosmetics applications this can provide.

Why is autophagy essential?

Taking us through why autophagy is essential for cells, Keedon Park, CEO, Incospharm relayed that “cells are relentlessly facing various stresses, from the nutrient deprivation and malfunctioning proteins to oxidative, UV damages, and microbial infections”.

Identified as a recycling machinery of cells, autophagy was first described as a self-eating, cellular energy maintenance process, Park noted. However, further investigation revealed that it encompasses much wider roles including innate cellular protection system.

Similar to the innate immune system, which is a germ-line encoded immune system playing as a first line of defence against infection, autophagy also provides “cellular protection against both endogenous and exogenous damages”.

A protection system

Describing autophagy, as a protection system, Park noted that it is a “both a jury and prosecutor; deciding the fate of cells in response to cellular stresses and also helping to resolve the stresses”.

Without autophagy, whether it is a skin cell, liver cell or brain cell, intracellular accumulation of harmful materials, such as malfunctioning proteins, damaged organelles, and infiltrated microbes, is “uncontrollable”, leading to more severe symptoms such as psoriasis, diabetes, or Alzheimer’s disease.

“Therefore, autophagy is essential to all cells in the human body for maintaining the healthy or normal status, known as homeostasis,” observed Park.

Well-known signals

There are several well-known signals initiating the autophagy process. Change of cellular energy state, binding of specific molecules into a certain cellular receptor, which is called mTOR (mammalian target of rapamycin), and diverse cellular stress mostly targeting endoplasmic reticulum (ER).

Through these initiating signals, double-membrane enclosed, sphere-shaped micro-organelle (autophagosome) forms are later fused with lysosome (a waste removal specialist in a cell) to form autophagosome. This then eliminates target materials.

It is important to note that “autophagy is not a simple reaction”, but rather a well-coordinated, sequence of events. “Hence, it requires careful and thorough experiments for measuring the overall flux of autophagy events, not a simple change of one or two proteins, to identify autophagy modulating molecules,” Park added.  

The process in which autophagy inducing molecules reach into the cells differs from molecule to molecule.

Ageing process

“Autophagy is an innate process triggered by unfavourable conditions (malnutrition, ageing, stress) in the cell, and occurs naturally,” explained Park.

“However, when the cell is too aged, or due to malfunction of the autophagic process itself, the cell needs assistance from the external environment, such as autophagy inducing molecules.”

Considering the impact that this does have on skin conditions such as anti-ageing and anti-whitening, decreased autophagy activity is observed in aged skin as expected.

“It is also speculated that stimulation of autophagy process can correct or reverse the ageing process of skin cells. And we are now witnessing many evidences of skin anti-ageing effects of autophagy activators, including Incospharm’s Aquatide or MelaTrepein.”

Skin whitening

Whitening is another important area of interest for autophagy research. “During the skin pigmentation process, melanin pigments produced in melanocytes are packaged into melanosomes and transported into nearby keratinocytes,” said Park.

While many of whitening ingredients target the melanin production process in melanocytes, there is a possibility of unexpected side effects, such as unwanted damages on melanocytes. Stimulation of autophagy process in keratinocytes, however, can help to eliminate the already transported melanosomes in keratinocytes, while not acting on melanocyte.

This may then offer several benefits as whitening ingredients, such as avoidance of unwanted melanocyte damage or synergistic effects with other whitening ingredients.

What does the future hold?

Sharing why autophagy is such an important consideration, Park went on to say: “Nowadays, we are challenged by more and more stresses, including an increased amount of UV and particulate matter (PM).”

Unlike other kinds of anti-stress strategies that address specific points of action, autophagy is an innate cellular protection mechanism and activation of autophagy reaction can provide holistic protection for cells and, ultimately, skin.

Looking ahead, therefore, the industry requires an “extensive understanding about the mode of action for developing cosmetic ingredients for autophagy application”, Park concluded.

The second part of this article will be published on Monday 16th July 2018.