How and Why do We Age?

What are the molecular and cellular mechanisms that regulate ageing and can we delay ageing by targeting these processes?

The cellular and molecular hallmarks of aging are considered to be:

1 DNA instability. Although our cells can repair most DNA damages, some DNA lesions are not properly repaired and are instead fixed as mutations in our genome which can impair cellular functions.

2 Shortening of telomeres. Telomeres are the ends of the chromosomes. With each cell division, a piece of the telomeres is lost and the chromosome becomes shorter. When a certain minimum length is reached, the cell becomes inactive and no longer divides.

3 Epigenetic alterations. Some of the changes naturally occurring in the epigenome are misplaced, added in the wrong place, or lost. As a result, the control over gene activity is impacted.

4 Loss of protein function. With age, proteins are increasingly damaged due to normal cellular processes. Damaged proteins can’t longer perform their normal work or they can clump together, which can have a toxic effect on the cell.

5 Deregulated nutrient sensing. When cells are constantly exposed to excess nutrients, the cellular mechanisms that recognize nutrients become desensitized failing to respond properly to the signals that normally regulate cellular functions.

6 Mitochondrial dysfunction. Mitochondria are essential for the production of energy by utilising the oxygen we breathe in. However, this process sometimes produces damaging free radicals.

7 Cellular senescence. Cells that have entered a non-dividing state are called senescent cells. These cells can release harmful molecules, which can negatively influence other cells.

8 Stem cell exhaustion. The ability of stem cells to divide, and the ability to divide only when new cells are needed, decreases with age.

9 Altered intercellular communication. Ageing not only changes the signals sent by cells, but also the ability of recipient cells to respond to these signals.

These 9 hallmarks of ageing answer the question of How do we age? But why do we age at all? If there are processes in our cells that can extend our lifespan, why have organisms not developed mechanisms to do so?