Genomic Instability: A Root Cause of Aging – Part 1
Dear Longevity Insider,
Age is the number one independent risk factor for all chronic diseases. As stated in my previous article, aging is the many processes of cellular damage accumulation in the body and these are known in the scientific literature as the Nine Hallmarks of Aging.
The first four hallmarks – genomic instability, telomere attrition, epigenetic alterations, and loss of proteostasis – are considered primary, since they are believed to be actual causes of aging and have a definite negative effect on DNA. They could be what firstly initiates cellular damage, which then leads to accumulation and progressive loss of function.
The next three hallmarks – deregulated nutrient-sensing, mitochondrial dysfunction, and cellular senescence – are called antagonistic, as they ultimately respond to the damage caused by the primary hallmarks. However, they are initially designed to have protective factors. It is only when bodily conditions become chronic and/or aggravated that they contribute to cellular damage.
The last two hallmarks – stem cell exhaustion and altered intercellular communication – are thought to be integrative hallmarks because they “directly affect tissue homeostasis and function.” These come into play once the accumulated damage caused by the primary and antagonistic hallmarks can no longer be stabilized. Once this happens, functional decline is inevitable.
Defining the genome
In this article, we will look at the first hallmark, genomic instability. It is a root cause of aging, thus the reason it is categorized as one of the primary hallmarks of aging. But first, let’s go back to high school biology and take a look at what comprises the genome.
We’re all familiar with the visual of the double-helix structure that is DNA – the complete set of instructions that we are all born with. This very long DNA molecule is made up of smaller units called nucleotide bases – of which we have 3 billion! They vary ever-so-slightly in each of us, which makes us all unique!
Combinations of these DNA bases form our 20,000 to 25,000 genes, which contain all of the information needed to produce one or more proteins. Some genes determine our physical characteristics, and some can influence our susceptibility to certain conditions and illnesses.
Our DNA is tightly woven around proteins to make structures known as chromosomes. We inherit 23 pairs from our mother and father, and they are stored in the nucleus of our cells. Some DNA is also stored in the mitochondria, which is like a power generator for the cells. Collectively, this is known as our genome. There is one copy of our genome in nearly every cell of our body, and every one of those cells knows what their jobs are.
On Thursday, we'll talk about "damage control."
You don't want to miss it!
To your longevity,
Anil Bajnath MD
CEO/Founder, Institute for Human Optimization
Chief Medical Officer, Longevity Insider HQ