Cells are very complex and contain structures (organelles) that perform various functions. New organelles are being identified every year, and the cell is still not completely understood. Basic organelles in the cell include the nucleus (the cell’s engine), the mitochondria (the cell’s energy supply, or gas tank), the endoplasmic reticulum (the cell’s factory), and the lysosome (the cell’s garbage disposal).

This week’s email focuses on the lysosome, which breaks down or recycles cellular waste products into basic components that can be used as raw materials to make new cellular products. Lysosomes also break down toxic waste into less harmful components. Lysosomes are made up of many different enzymes, and each enzyme has a specific function. In order for a lysosome to do its job of ridding cells of garbage, it needs 3 things:

1. The correct enzymes

2. The ideal pH (or acidity) for that enzyme to work. (Different enzymes prefer different pH environments.)

3. Energy produced by the mitochondria, also known as ATP. The lysosome membrane contains a pump that requires energy (ATP) to pump hydrogen ions into the lysosome to maintain its acidity.

There are many hereditary diseases that are caused by liposome dysfunction, and these conditions allow cellular garbage to accumulate inside the cell. These are called lysosomal storage diseases. Examples include Tay-Sachs disease and Gaucher’s Disease. Lysosomes are not able to degrade all cellular junk and the leftover garbage which is not broken down is called lipofuscin.  The buildup of lipofuscin is seen in aged cells (it is fluorescent so it is easily visualized under a microscope). Studies have shown that oxidative stress by free radicals leads to an increase in lipofuscin. Lipofuscin accumulation hampers the lysosomes’ ability to work by disrupting acidity and the supply of enzymes. In other words, the buildup of lipofuscin cellular trash plays a role in skin aging. Treatments to prevent this form of aging would have to do one of the following:

1. Enhance lysosomal function

2. Increase breakdown of lipofuscin and cellular junk

3. Decrease free radical formation

Background Information on Free radicals and Oxidative Stress

Free radicals are formed naturally through normal human metabolism, but can be produced as a result of external factors like UV exposure, air pollution, smoking, radiation, alcohol use, exercise, inflammation and exposure to certain drugs or heavy metals such as iron. Free radicals, also known as reactive oxygen species (ROS), are compounds formed when oxygen molecules combine with other molecules yielding an odd number of electrons. The presence of free radicals is called “oxidative stress” because it is a stress on the system caused by oxygen. An oxygen molecule with paired electrons is stable and nondisruptive. When ultraviolet light or other stresses cause oxygen to lose an electron, a free radical or “reactive oxygen species” is formed. Oxygen with an unpaired electron is “reactive” because it seeks and seizes electrons from vital components of the cells, leaving them damaged. DNA, cellular proteins (including collagen and elastin) and cellular membranes may all be adversely affected by activated oxygen species. In last week’s email, we learned that free radicals can also lead to protein crosslinks, which lead to aging. Oxidative stress also leads to an increased accumulation of lipofuscin.

What to do about it

Enhance lysosomal function

Scientific discoveries occur first in areas of severe disease because these advances are most needed and have the most funding. Gaucher’s disease, which is a serious disease caused by a lack of a lysosomal enzyme, is successfully treated with intravenous infusion of the missing enzyme. Genetic treatments are being developed for Tay-Sachs disease. At this time, there is no published data on skin aging or skin appearance and the role of lipofuscin. Although it is likely that skin with increased lipofuscin appears older, this research has not been done. It is not known at this time if there are any particular enzyme deficiencies that lead to increased skin aging, but it is very probable that there are. We know that certain families have a tendency to have less aged skin than others and that genetics likely play a role. We do not know if liposomes are involved, but it is a reasonable hypothesis that they would be. If the enzyme deficiencies that lead to increased skin aging are discovered, then development of new therapies can begin. At this time, the skin related therapies are probably at least 10 years away.

Increase breakdown of lipofuscin and cellular junk: In his book, Ending Aging, Dr. de Grey eloquently explains that there are bacteria that can break down lipofuscin. Harnessing the power of bacteria to clean out or cellular garbage is intriguing, but certainly many years away from being incorporated into anti-aging facial creams.

Decrease free radical formation: The more we learn about skin aging, the more we realize the importance of antioxidants. Much attention is focused on external and internal use, and using combinations of antioxidants for optimal free-radical protection. In order to be considered biologically “active,” antioxidants taken orally must be absorbed and shown to raise antioxidant levels in the skin. Topical products must be absorbed into the skin and delivered to the target cells in the active form, and remain there long enough to exert the protective effects. Some antioxidants are very unstable; therefore, some ingredients such as vitamin C become oxidized and inactive before reaching their target within the skin. Stabilizing ingredients through proper formulation and packaging in order to minimize air and light exposure are challenging tasks. Antioxidants’ ability to penetrate the skin is also dependent on many other factors, including the molecular composition of the ingredient, its pH, whether it’s fat-soluble or water-soluble, and even the formulation of the product’s vehicle (or base). So while antioxidants are proven to be an valuable part of any skincare routine, a lot goes into ensuring an antioxidant is effective.

We hope that you enjoyed the fourth installment in our series about “The 7 causes of Aging.” Stay tuned for next week when we’ll discuss “Junk accumulating outside cells” as a cause of aging.