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Why we Age

Everyone accepts they will age, but few understand why. Let’s try to solve the age old problem of why we age (I did warn you this blog was a puns special).

Let’s first look at how to measure your biological age (basically, more precise ways than looking at a mirror). One way to measure the aging process is via telomeres. These are commonly described as the end caps of your chromosomes (similar to end caps of laces), and just like the tips of your laces, telomeres are nature’s way of protecting your chromosomes from fraying. Every time a cell divides, the telomeres get a little bit shorter and this becomes a neat way of measuring how many times your cells have undergone the division process. Basically, shorter telomeres = older biological age. 

Another way to measure your biological age is via the volume of senescent cells. These are cells that have become rundown and cause inflammation in your body.This is especially worrisome as inflammation is the root cause of almost all chronic diseases in one way or another. These cells have weakened intercellular communication and mitochondrial dysfunction. More senescent cells = aging.

Along with these, there are other hallmarks of aging cells. These include genomic instability (faulty gene activation or suppression (which typically leads to cancer), epigenetic alterations (your genes being turned on or off depending on your environment), loss of proteostasis (faulty protein synthesis, folding, trafficking and degradation), deregulated nutrient sensing (cannot absorb and transform nutrients to energy effectively), and stem cell exhaustion (the potential of your undifferentiated cells to transform into a specific kind of cells deteriorates). 

Before the outer symptoms of aging show, these are the inner symptoms of aging in your body. But what is actually triggering these aging hallmarks?

Theories of aging extend back to the dawn of human wonder. There are ancient theories, such as the 6th century BC Athenian statesman Solon’s perception of old age as the last of ten life stages, and then there are more modern theories such as the programmed theory: where hormones control the pace of aging via a biological clock, and the gene theory: our lifespan and healthspan relies on the genes we inherit.

The current theory as accepted by Dr. Sinclair is that aging occurs due to loss of information in our epigenome. Epigenome refers to the chemical changes in your DNA via changes to your histone proteins (proteins that your DNA is coiled around) and methylation (chemical signalling markers placed on DNA in certain locations). It is crazy to realise that every cell in your body has the exact same DNA information, but it is the difference in expression (which genes are switched on/off) that determines how these cells differentiate. There are different ways your DNA is packaged in your cells, and this determines which genes are open to be read and transcribed into protein (and hence perform a function), and which genes are coiled up and out of reach. 

How does loss of information in the epigenome cause aging? 

Well it’s your epigenome that determines which newly divided cell differentiates into which particular cell type. If there’s not the appropriate signalling and your cells can’t properly read your DNA, then they don’t know what they should differentiate into and could transform into any type of cell. This leads to cells going haywire, not functioning as they should and hence increasing vulnerability to cognitive and physical dysfunctions, and voila: aging! 

Now you may be wondering, why are there more epigenome errors overtime?

Well, every time you have an environmental assault, which is very often and unavoidable, (such as exposure to sun, pollution, toxins, preservatives, etc) your DNA is damaged.To repair your chromosome, your cells have to unwrap your DNA from the histones, repair it and then join it back to its previous state via histones and methylation.This methylation and histone wrapping happens accurately around 99.99% of the time, but that remaining 0.01% DNA error accumulates into aging. 

The crazy thing is we already have the technology to read your methylation pattern and figure out your biological age (which could be much different to your actual age based on your DNA repair hits) and even when you’re going to die. This is what scientists call the Horvath clock, where the more chemicals that accumulate on your DNA, the older you are biologically. If on the other hand, you have less of these chemical accumulations on your DNA than what is usually expected at your age, then the younger you will be biologically compared to your actual age, and will theoretically live a longer and healthier life.  

Professor Sinclair has shown this phenomenon in mice, where they have been genetically re-engineered to have more chromosome breaks, and reading their methylation patterns has revealed much more chemical accumulation on their DNA. These mice had more grey hair, hunchbacks, and dementia, and were found to be biologically 50% older than the control mice their age. 

However, this still seems to be one facet of the aging mystery; because even if hypothetically, you were to have a human with no environmental damage, they would still only be able to live around a maximum of 120 years without any intervention. Although, there is still much more research that needs to be funded to understand the full story of aging, we are living in an exciting time where we challenge age old notions of what’s possible. 

If you want to take a more in depth look at why we age and the current medical innovations to slow it, check out David Sinclair’s book: Lifespan: why we age – and why we don’t have to.