Why Do We Age? | Genomic Instability

Summary

During our lifespan our DNA becomes damaged, contributing to many problems given DNA contains all the instructions to build and maintain our body.

The Crumbling Code of Life and how it Contributes to Aging

Our DNA contains the instructions to build the proteins that make up our cells, and carry out most functions in our cells. During aging, our DNA becomes more and more damaged, contributing to the aging process. 

More specially, DNA can become damaged in two main ways: 

Damage from the Outside

This kind of damage is caused by external factors, like physical (e.g. UV light), chemical (e.g. specific drugs, substances in cigarette smoke, toxic compounds) and biological damage (e.g. viruses). 

Damage from the Inside

This kind of DNA damage is caused by internal process, such as replication errors when the DNA is copied, reactive oxygen species (free radicals) produced by cellular metabolism, spontaneous chemical reactions, a dysregulated epigenome, and so on. 

These insults lead to all kinds of DNA damage, such as mutations, DNA strand breaks, chromosomes that disappear or get rearranged, telomere attrition and shortening, and so on. 

Every day, in every cell, tens of thousands of insults damage the DNA, but most of them are repaired, fortunately. 

The Aging Process

DNA damage is especially deleterious for stem cells. These cells create new cells that build up our tissues and organs. When the DNA of stem cells is too damaged, they function less well, or they  become cancerous, or they start to clonally expand (specific types of damaged stem cells take over the existing stem cell population). 

DNA damage also leads to the formation of senescent cells. Senescent cells stem from healthy cells that accumulate too much damage, putting them at risk of becoming cancerous. To prevent this, the body activates a safety mechanism, which prevents the damaged, dangerous cells from further dividing. The result is a senescent cell: a damaged cell that cannot divide anymore. However, senescent cells secrete all kinds of unhealthy substances that damage the surrounding healthy cells. 

There is some discussion among scientists whether DNA damage is really that important in aging. There are accelerated-aging diseases, like progeria, Werner syndrome, Bloom syndrome, Cockayne syndrome, Seckel syndrome and trichothiodystrophy, which are caused by DNA damage. However, these diseases do not encapsulate all aspects of classical aging. Children with progeria look like 80-year-olds, but they don’t have an increased risk of Alzheimer’s disease, cataract, or immunosenescence, which are typical aging symptoms. 

Another argument against DNA damage as the leading factor in aging involves cloning. When an animal is cloned, the DNA-containing cell nucleus of an aged, old cell is extracted (harboring a lot of DNA damage) and put it in an egg cell from which the nucleus has been removed. Despite being made up from aged DNA, the resulting animal is born young, showing that the DNA damage gets erased during the cloning process (after the old cell nucleus is put into the egg cell). 

Other studies show that Yamanaka factors can epigenetically reprogram old cells into younger cells, undoing their DNA damage. So it seems that organisms have the potential to substantially control and even undo their DNA damage, which could suggest that DNA damage is not an irreversible aspect of the aging process. 

Beside mutations in the DNA in the nuclei of our cells, the DNA in the mitochondria can also become damaged, leading to mitochondrial dysfunction. 

NOVOS’ Approach to Genomic Instability