The Masters Athlete Series: What is Aging?

There are basically three views on aging relevant to an athlete thinking about mitigating its deleterious effects:

• The Statistical View
• The Cell & Molecular Biology View
• The Systems View

Ghirlandaio, Domenico – An Old Man and His Grandson

The Statistical View

The statistical view on aging is based on a definition that – simple as it sounds – actually helps in making sense of many of the things we experience everyday. In its essence, aging is viewed as an increasing probability of dying with time passing. That’s trivial you might shout but then again it is not well understood by the general public. Most of us in January 2021 are still subject to some form of Coronavirus-related lock downs and you will have heard the rationale for it over and over again. COVID-19 is particularly dangerous to the old whom we must protect as the fatality rate increases exponentially with age. Well, indeed it does as does the fatality rate of everything else that you can possibly die off from other respiratory viruses such an influenza to all of the diseases of civilization 2.0 from diabetes to cancer. If your overall risk of dying increases exponentially so should the reasons for dying (at least on average).

Of course this definition does not help us in understanding why this curious statistical pattern should be true.

The Biological View

And in comes biology. Current biological thinking on aging is best summarized with two seemingly contradictory points that you have to contemporaneously hold in your head

• Aging is an expression of a pretty complicated interplay of many components
• It is pretty simple (at least in animal models) to find single interventions to make you live longer

The Hallmarks of Aging

Let’s start with the complicated: inspired from ideas in cancer biology, Guido Kroemer and colleagues have published a very influential review in 2013 that defines the biological hallmarks of aging of which there are nine in total:

• The first type are those are called primary hallmarks and are thought to be the underlying causes of something going wrong. These are (1) genomic instability (i.e., your DNA getting damaged by the environment but also by the byproducts of your own metabolism), (2) telomere attrition (i.e., the protective ends of your chromosome getting shorter with every cell division), (3) epigenetic alterations (i.e., damage to all the stuff that makes sure your DNA can properly replicate) and (4) loss of proteostasis (i.e. the inability to keep your proteins that do the work properly folded)
• As a result of the first type, the organism reacts with a second type called antagonistic hallmarks which first try to defeat the damage. The first and very important one is (5) altered nutrient sensing. In its very simplest form, the cell has a nutrient sensing system that is very similar for all animals and even yeast across evolution. It sees if there is enough food out there. If there is, it can afford to divide and grow and if there is not it rather protects what it has and waits for better times but both need to cycle and be in balance. The same is true for (6) altered mitochondrial function. Mitochondria produce reactive oxygen species as a result of stress which are a signal to up the cell’s defense but again too much is bad as it overwhelms the defense capabilities. And last but not least you have (7) cellular senescence or programmed cell death. If cells go bad and are beyond repair, they are made to die but too many dying cells of course are a problem all by itself.
• The third category finally are called integrative hallmarks because they lead to what you see (the phenotype) as a result of all that happened previously. They are (8) stem cell exhaustion and (9) altered cellular communication. Stem cell loss leads to trivial results such as hair loss but also more serious results such as reduced repair of muscle and bone while altered cellular communication is most prominently on display in the gradual loss of the competence of the immune system to accurately detect and destroy foreign invaders.

The Interventions – How to live longer

You might agree with me that that was rather complicated and often a bit hand-wavy especially when it comes to the „proper balance“ of the mechanisms of defense or antagonistic hallmarks. Why then do we think it is simple overall? Well, it is quite easy to make animals live longer – and while experiments in humans are a bit more ethically challenging, observational results point in the same direction as the results from animal studies.

Here is what you can do to make an animal/human live longer:

• Give them anti-aging drugs that primarily affect the nutrient-sensing pathways (metformin and rapamycin)
• Restrict their calorie intake (fasting for humans)
• Mutate single genes that are (mostly) involved in the same pathways of nutrient sensing – easier for worms that humans
• Make them exercise – easier for humans than worms

In my view, exercise is special as it speaks directly to maintaining the cycling and balance between competing systems that only appear to be antagonistic but really are synergistic in nature. Yes, a long run activates many of the same pathways that signal nutrient scarcity but then again, a strength-session activates the competing and insulin-dependent growth pathway for hypertrophy and many sessions will do both at the same time (if in different places).

The Systems View

So how do we have to think about what aging actually does from a system performance point of view.

Humans are complex systems. Complex systems are characterized by many individual components that are connected with each other and give rise to patterns to which they themselves react. An example is cars and traffic. Cars generate traffic but also react to it individually.

Humans are a complex system that maintains homeostasis or a relatively stable internal state (e.g., body temperature) despite changes in the environment (e.g., the weather). Aging can then be defined as a decrease in the dynamic capacity to return the body to its homeostatic state. If you are a masters athlete reading this, you can probably remember your younger self and how much easier it was back then to get away with a lack of sleep or a likely much junkier diet that you adhere to today. Equally, one of the differences between training masters athletes and younger athletes is that masters need a lot more recovery time (or time to return to homeostasis).

There are two important implications to this view of aging:

• First, you need to keep challenging the system to keep its own defense mechanisms up. In my view, this is why it is so important to include strength training and high intensity units (with adequate recovery) into your routine. The system is only as good as the ability to deal with external challenges to homeostasis so challenge it. Almost any acute challenge is good the same way that all danger comes from chronic exposure to disruptions of homeostasis (stress, inflammation, lack of exercise, nutrient abundance, …)
• Secondly, a complex system can break down at a thousand points and often in surprising ways which are caused by small changes to initial conditions. Here is a example from 2006 and the electrical power grid:

„Germany’s biggest power supplier said on Nov. 15 that human error was to blame for the electricity cut that plunged parts of Western Europe into darkness on November 4. E.ON said the switching-off of an electricity line over the Ems River in western Germany to allow a cruise ship to pass through, coupled with the outage of a second transmission line, „set off the domino effect which led to the temporary disconnection of the European inter-connected power grid.“

Industry News, Nov 15, 2006

If you know your weak spots, do not ignore them but pay particular attention to safeguarding the function of the entire system. If we are honest, we can probably identify some of our potential break-points simply by looking at family history.

In one of my next posts, I will discuss how to read-out the state of your system (other than getting to know and listening to your body) and its dynamic homeostatic capacity.