What are the 9 Hallmarks of Ageing?

As we have begun to understand, ageing is cell damage. This damage leads to all kinds of symptoms, ranging from the simplest example of wrinkles to more severe diseases. If you can slow down ageing, you can actually stay healthier longer.

An increasing number of studies suggest the presence of a “metabolic clock” that controls ageing. This clock involves the accumulation of metabolic alterations and a decline in metabolic homeostasis and biological fitness. The key to tackling ageing and promoting longevity lies in targeting the underlying age mechanisms.

The key to tackling ageing and promoting longevity lies in targeting the underlying age mechanisms.

A decade ago, a framework was created to describe all known researched factors that contribute to ageing. These have been termed the “9 hallmarks of ageing”. The hallmarks have been proven to slow down or aggravate ageing in experimental settings. Many scientists are now building upon this framework. They developed a consensus model, noting what each hallmark of ageing should exhibit during normal ageing. Molecules and lifestyle habits have already been identified that target the hallmarks of ageing and that can rewind the biological clock.

While the hallmarks of ageing are determined mainly by our genetics, environmental factors can cause or exacerbate them also.

While the hallmarks of ageing are determined mainly by our genetics, environmental factors can cause or exacerbate them also. Each hallmark contributes to the damage that occurs and accumulates with age and is ultimately responsible for age-associated pathologies. The hallmarks of ageing determine the difference between chronological age (how many years since you were born) and biological age (how the ageing process has affected your body’s physical and mental functions and appearance).

There are nine cellular hallmarks of ageing have been described so far. These are:

Primary Causes

1. Genomic instability (errors in your DNA)

The progressive accumulation of damage in DNA is caused by external agents, such as certain harmful chemicals, pollutants, ionising radiation and so on. Cells lose the ability to repair them and these mutations cause significant functional damage to the cells.

2. Telomere shortening (loss of DNA protection)

These are the final parts of chromosomes which, like caps, protect the DNA (making it more stable) but which “wear out” at each cell division.

3. Epigenetic alterations (genes are wrongly turned off or on)

Biochemical reactions that control the ” switching on” and “switching off” of genes also affecting the ability to repair DNA damage. These genetic activities are environmental and lifestyle sensitive.

4. Loss of proteostasis (accumulation of proteins inside cells)

All cells have mechanisms of “quality control” of the proteins that contribute to cellular functions. If a protein is defective or altered in any way to lose its original function, the cells discard it. When the “cleaning” mechanisms do not work properly, the damaged proteins accumulate and create damage that may be permanent.

Accelerating Causes

5. Nutrient sensing (cells absorbing too many nutrients)

This refers to alterations within the metabolic mechanisms that allow the correct perception of nutrients requirement. The best known example is the loss of response to insulin (insulin resistance), the antechamber of diabetes. In order to control blood glucose, the cells of the pancreas are forced to produce more and more insulin until they run out of stock..

6. Mitochondrial dysfunction (internal power plants breaking down)

Mitochondria represent the energy centre of the cell. The mitochondria contain their own DNA that is constantly subject to damage from oxidative stress, because the reactions that take place in the mitochondria constantly produce free radicals that damage the DNA and the proteins that constitute the mitochondria themselves.

7. Cellular senescence (zombie cells)

The cellular senescence allows an accumulation of “zombie cells” that inflame the tissues. Although they no longer function, these cells do not die because they have lost the ability to self-eliminate at the end of their life cycle. They cause damage to surrounding cells by producing inflammatory factors (cytokines) which in turn create an inflammatory microenvironment that damages the tissue itself.

When there’s too much damage

8. Stem cell exhaustion (lower tissue maintenance and repair)

This refers to the loss of tissue regenerative capacity linked to the depletion of the stem cells, the source of adult (differentiated) cells that build up organic tissues architecture and specialise their function.

9. Altered cellular communication (a vicious cycle of damage)

This refers to the intracell communication alteration, with the production of inflammatory molecules. It is one of the most studied mechanisms of ageing, also called inflammaging, and it is also one on which it is possible to intervene effectively with lifestyle interventions (diet and moderate regular exercise) and with targeted nutritional supplements.

In conclusion, what we have learnt is that our bodies are dynamic, molecular machines, and that how we age is not predetermined by our literal age. We can thus easily influence the ageing process with specific, healthy lifestyle choices that can make a dramatic difference in how well we age and how long we live.

FY