Our bodies are composed of 10 trillion cells. We tend to think of the differences between cells for instance “heart disease”, “liver disease”, “dementia”… Yet 100% of the DNA and 90% of our cells proteins are the same in all cells. It is the 10% of different protein expression that leads to the difference between a heart cell and liver cell – and on which we tend to focus.
This leads us to ignore the underlying similarity between cells and the fact that the underlying mechanism of aging is the same in all the different cell types (except stem cells). So cells from the heart age in the same way as cells in the liver and cells in the brain… This actually makes it easier for us to protect against aging as there is not a particular mechanism for aging in the heart which does not apply to the liver which does not apply to the brain etc… If there was a different mechanism of aging for each organ this would make it difficult and potentially impossible for us to protect against aging overall as interventions that may help aging in one organ may make it worse in another.
It is to this single mechanism of aging and how to influence it that we now turn –
Normal Young Cell
All our cells have the same basic processes for keeping themselves alive and functioning. They usually also have special functions, for instance a heart muscle cell contracts, but this obscures the fact that the majority of processes in each cell in each tissue are the same. It is on these processes that aging exerts its principal effect.
This diagram is of a normal young cell, the numbers apply to the following processes-
1) The production of high energy molecules to power the cell is achieved by the processing of molecules such as glucose by mitochondria-the “power generators”
2) The design instructions “blue prints” for the production of proteins is encoded in the DNA. The DNA is transcribed into RNA each molecule of which usually contains the instructions for one specific protein.
3) The RNA travels out of the nucleus to a ribosome which is often on endoplasmic reticulum (“protein assembly factory”) just outside the nucleus.
4) The proteins are the crucial efffector molecules in the cells forming enzymes, receptors…etc. They allow the cell to process things and perform functions. Most proteins are used for basic cellular processes to keep the cell functioning. However the ones that are most obvious are those that perform specific cells to perform specific processes such as proteins that allow the contraction of muscle.
5) The proteins and cell organelles will over time become damaged so a waste disposal system is needed-otherwise the cell will become overwhelmed by waste.
Cell Control Mechanisms Involved in Aging
NAD (1) (nicotinamide adenine dinucleotide) preserves mitochondrial function and acts as a cofactor for Sirtuin activity.
Sirtuins (2) stimulate mitochondrial, alter the reading of the DNA and stimulate the repair of DNA.
The mTOR gene (3) stimulates protein production by the ribosomes on the endoplasmic reticulum.
The FOXO gene (4) stimulates the “waste disposal” mechanism – principally the lysozymes.
Both genes are under the influence of IGF-I (insulin like growth factor 1) which increases the effect of mTOR and decreases the activity of the FOXO gene. This leads to a preponderance of protein production compared to protein breakdown. This will tend to lead to the accumulation of proteins both functional and dysfunctional in the cell.
Cells in Middle Age to Later Life
1) NAD decreases with age leading to less protection of the mitochondria both directly and through an effect on decreased Sirtuin activity
2) mitochondrial number and function are decreased and so the energy available to processes in the cell decreases with age
3) partly because of the lower Sirtuin activity the DNA is not repaired adequately and DNA damage accumulates
4) there is a buildup of waste products in the cell as the cell ages. It can be seen that this is important for longevity as stimulation of the “waste disposal” system leads to a longer lifespan.
5) senescent cells produce chemicals which impair and damaged surroundings cells speeding up aging.
6) information in the local tissue and elsewhere in the body has been shown to speed up aging.
7) the microbiome, principally the bacteria in the colon, has also been shown to influence aging.
These are only some of the mechanisms involved in aging, there is also evidence for other mechanisms such as the length of telomeres at the ends of chromosomes, stem cells in the hypothalamus, exosomes containing micro-RNAs and enzymes…