Contemplating Longevity Part 4: Mechanistic Theories of Aging

At the time of this writing, COVID-19 has the globe in a state of uncertainty as the virus spreads and we await a treatment.

But there is another condition that is 100% fatal that also has no known cure (yet). Aging.

For the community of scientists who view aging as a disease, a lot of the focus is on the pieces and parts that make us who we are.

To date, there has not been a discovery singular item that explicitly causes or delays aging. The thing is, it seems to be a bit of a game of whack a mole.

  1. Scientist will find something that looks a cause of aging. 
  2. Then they try to interrupt that thing and see what happens. 
  3. Maybe they stop the phenomena successfully, but aging still continues. Or aging may slow in some cases but not others.
  4. Go back to 1.
What sort of things have they found along the way? How well do we understand our machinery?

The Sophisticated Robot

Let's imagine we are are a very sophisticated robot. What would cause us to cease to function?

  1. Sudden failure of a critical piece of equipment - the heart stops pumping or brain mainframe shuts down. To avoid this, we might engineer some solutions:
    1. Redundancies - let's duplicate where we can so we can have a backup (kidneys, lungs)
    2. Repairing tools - maybe we can insert some nanobots to repair damages as they occur, so long as the damage is not too catastrophic.
    3. System independence - where we can, let's shut down one system to save another.
  2. A cascading series of failures - much like trying to plug holes in a dam, we might be able to handle damage in one area pretty well, but at a certain point we topple like dominoes. The good news we are rather resilient robots. Our machine can keep operating with a lot of damage. Eventually we will get to where the next piece of damage will cause item 1 to occur.  This concept is known as the Reliability Theory of Aging
  3. Damage accumulation - this can cause either of the above to occur.  As we rust (you may have heard about oxidative stress), or pick up junk from being in the world, we just don't operate as well. Damage to our fuel cells (mitochondria) is particularly problematic.
  4. Wearing out - similar to above, if we were able to operate in lab, completely safe from external damage, would we last forever? We don't really know. What we do see is things like the Hayfleck Limit, when cells stop dividing, and Telomere shortening. (Note that telomere length by itself doesn't predict long life, rather, it's rate of decay indicates aging effects.)
  5. A glitch in the code -  how do we coordinate all these intricate systems that keep our robot running? We have circuitry all over and in a variety of formats (nervous, hormonal, epigentic, micriobial). If any of it becomes corrupt (hacked by a virus) for instance, or a poor copying process, we might have fatal results. We will look at the genetic code in a little more detail.

Is there a Longevity Gene?

Genes are the code behind the human interface. The study of genetics in the context of longevity has yet to detect a singular gene that forces the program to shut down. Rather, what we have is a combination of genes that seem to start or stop certain "programs."  

These programs have downstream affects on the body and influence aging. Some programs seem to be proactive, with internal triggers to make that happen. Other programs seems to be reactive, only turning on if there is the right external stimulation, such as stress.

In a pretty spectacular development, scientist recently were able to use gene editing to halt a condition called "progeria syndrome." This condition causes accelerated aging in animals and people. It is caused by a genetic mutation. By editing the DNA and 'fixing' the mutation, the symptoms of the condition went away in mice!

We are constantly discovering more programs and more on/off switches in our code, but perhaps a more interesting question is  - what flips the switches?

Signal and Noise?

David Sinclair, PHD is an aging researcher and author of Lifespan. This text introduces the Information Theory of Aging. Our body constantly receives signals and if that signal gets lost or distorted, we might end up with aging. The signals activate repair, or deactivate growth and renewal. So by controlling noise, and passing different messages, we might get to a place where the signals we send and receive are that everything is great, all systems go!