HealthCommentary

Exploring Human Potential

Worried About Aging? Look Below The Skin At Lysosomes.

Mike Magee MD
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When most of us worry about aging, we look at our reflection in the mirror, and see what’s going on above the skin. But recent discoveries tell us that aging may be all about what’s going on below the skin, and inside our cell factories.1 It’s becoming clear that if we’re going to maintain our youth and vitality as long as possible, we need to think microscopic first and macroscopic second. And that means knowing the names of two critically important cell organelles – the lysosome and the proteasome.

These “somes” are microscopic recycling machines that together keep the cells “young”.1,2 The lysosome is a membrane enclosed container filled with enzymes that are able to digest and dismantle portions of a cell’s apparatus that are weakened or damaged. Proteasomes are smaller tube like structures capable of ingesting broken pieces of your intra-cellular protein and recycling these pieces to build brand new proteins.2

So basically, the “somes” are there to give each and every one of your trillions of cells the capacity to regenerate itself, by taking worn out and damaged microscopic parts, dismantling them, and then sending the building blocks back to the assembly line, or the energy back to the cells’ factories to keep the healthy cell machinery going.

Why is that so important? Well let’s step back for a moment. The key to normal function is a series of intricate checks and balances. Many of the microscopic actions taken inside our cells are intended to be short-lived. For example, a protein produced may be required for only a few minutes, and after that could confuse or disrupt other cell functions. To avoid this, the “somes” are time programmed to take this protein out.1,3 A second purpose is more evolutionary in origin. Humans’ sources of nutrition are not consistent. At times of famine, our bodies are deprived of chemical renewal, and at times of plenty, may be overwhelmed with new chemicals in excess of what we need immediately. By having “somes” inside our cells, we have the capacity to selectively access our own, least valuable cell chemicals and digest them to keep our cells going during tough times. That may occur dramatically with full blown famine, or less dramatically when you ignore the need for a snack between meals.1,2,3

Finally, there’s the issue of aging. As we age, structures do show wear and tear. The challenge is to rejuvenate constantly. The “somes” help us do that. And now there is increasing evidence that if they fail, old and broken cell junk may accumulate and cause big problems. For example, the protein deposits commonly found in the nerve cells of Alzheimer patients, believed to be associated with the loss in mental function over time, may reflect “somes” that have taken the day off.1,2,3

While lysosomes were discovered way back in 1955, it is only recently the researchers, studying models from yeast to mice, have figured out what “turns them on”.4 Naturally, they are activated by fasting, which instigates a form of internal cellular cannibalism, whose side effect is to clear out the mess of damaged or worn out chemicals through digestion and recycling. The second way to get them going is to introduce a chemical called TFEB which turns on cellular genes which control lysosome activity.5

What’s to be made of all this if it proves out?  Well, first, as you age, it may be important to eat less to keep your “somes” active in their clean up functions. Second, careful studies of master switches such as TFEB and it’s association with Alzheimer’s and other diseases may bear fruit. We may be able to create medicines to activate TFEB. And third, this line of research may offer hope to the many who suffer debilitating and degenerative diseases as they age.

For Health Commentary, I’m Mike Magee

References:

1.   Tibor Vellai, Krisztina Takács-Vellai, Miklós Sass and Daniel J. Klionsky. Trends in Cell Biology, Volume 19, Issue 10, 487-494, 01 September 2009

http://bit.ly/1eyi8h

2. Zimmer, C. Self-Destructive Behavior in Cells May Hold Key to a Longer Life. NYT. October 5, 2009. http://bit.ly/anh6u

3. Zhang C, Cuervo AM. Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med. 2008 Sep;14(9):959-65. PDF

4. Christian de Duve. NNDB.  http://bit.ly/2uIXQ

5.  Gene Network Regulating Lysosomal Biogenesis and Function. Marco Sardiello, Michela Palmieri, Alberto di Ronza, Diego Luis Medina, Marta Valenza, Vincenzo Alessandro Gennarino, Chiara Di Malta, Francesca Donaudy, Valerio Embrione, Roman S. Polishchuk, Sandro Banfi, Giancarlo Parenti, Elena Cattaneo, Andrea Ballabio.  Published Online June 25, 2009. Science DOI: 10.1126/science.1174447 http://bit.ly/K3gCk

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