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Why do we age? Part 3 of 3: Here's the why, but can it be stopped?

SciManAug 9, 2019, 7:44:54 PM

Thus far I have written about two models that attempt to explain why we age. The first is the wear and tear model (https://www.minds.com/ScienceMan/blog/are-we-programmed-to-age-962695083828350976) - that holds that we age because of the constant assaults of life on our body and cells -- wearing down like the parts of an automobile.   The second model is the programmed aging model (https://www.minds.com/ScienceMan/blog/why-do-we-age-part-2-of-3-are-we-programmed-to-die-970421381307936768) that posits aging is an evolutionarily inspired mechanism that causes cells and organs to break down on schedule. Although both models have good evidence to support their validity, each has faults.  So why do we age?

Sometimes I have found that when there are two wonderfully competing theories and the question becomes is it A OR B - the most satisfying answer turns out to be - YES. 

The hallmarks of aging - described in greater detail in: https://www.minds.com/ScienceMan/blog/are-we-programmed-to-age-962695083828350976

As I discussed in my first blog post, aging is associated with several hallmarks of systemic and cellular decline - the symptoms of wear and tear. However, these declines are challenges faced in our youth as well, but do not present in such a degree as when we get older -- why?

The reason is that for each of these challenges, organisms have signaling networks that instruct cells on how to repair the damage. For example, telomeres, the DNA repeats at the end of chromosomes, shorten after each DNA replication, ultimately killing the cell if it gets too short. Yet, some cells use an enzyme called telomerase that is able to extend the length of these telomeres. Likewise, signaling networks are available to handle most any emergency, whether it is DNA repair, mitochondrial dysfunction, stem cell exhaustion and more. Most "anti-aging" strategies affect just a few of these hallmarks (i.e. Resveratrol increases sirtuin activity, caloric restriction affects the mTOR pathway) -- but no agent yet know can correct all of these problems - thus aging goes on.

Additionally, as we get older these protective mechanisms slow down - but why?   Perhaps programmed? 

Indeed - aging happens because our defenses against the wear and tear of time are being told to stop - but how?

The answer is epigenetics - the system of control that dictates which of our genes are turned on and off. Essentially, the genes we need to turn our cells young again are hidden deep in the twisty knots of histone proteins - silenced

A newly emerging field in aging research is looking to break the code. The field is called cellular re-programming and is making great strides:


In a study by Ocampo et al, researchers have created a mouse model system whereby they can turn back on a set of four genes (Figure below) that typically instruct a developing embryo to grow properly

Investigators turn on the Yamanaka factors in mice by use of a tet-on system, in this case by providing doxycycline to the mice, the genetically altered mice will produce the four proteins in various cell types for just two days - but then are cycled off for 5 days, before repeating (So the genes do not stay constantly on).

Survival in mice that had the four factors turned on by DOX -- LAKI mice are a strain of mice that die after about 18 weeks of age (compared to ~130 weeks in a normal mouse) -- the LAKI 4F is a mouse that has been genetically modified to have the 4 factors.

At the end of the study, the investigators found 50% survival increased by nearly 33% in a model of accelerated aging. Additionally, they found several tissues had improved appearing more "youthful" (below).  

Reprogramming causes several tissue types to appear more like what is seen in a healthy young wild-type mouse. 

Furthermore, a recently published study demonstrates reprogramming rescued aging-induced vision loss in mice:


Thus as our understanding of the mechanisms that make us older expand, so will our hope of combatting the age-associated declines that also increase our risk of heart disease, cancer, diabetes, arthritis, and more! As the layers of complexity are peeled back, we are begging to understand that perhaps aging isn't inevitable after all!

I look forward to your questions and comments below!