Hallmarks of Ageing

Take a seat.

Ageing has long been treated as a single, undifferentiated process — an inevitable and largely mysterious decline that begins at some point in midlife and proceeds on its own terms regardless of what we do. That understanding is now significantly out of date.

In 2013, a research team led by Carlos López-Otín published a landmark paper in the journal Cell -identifying nine distinct biological mechanisms underlying the ageing process. These became known as the Hallmarks of Ageing. 

A decade of intensive research followed, and in 2023 the same team published an updated framework expanding the hallmarks to twelve.

What this work established, with scientific rigour, is that ageing is not one thing. It is a collection of identifiable, measurable, and in a growing number of cases, addressable biological processes — each distinct, each consequential, and each increasingly the subject of serious research into intervention.

The twelve hallmarks as they currently stand are these:

Genomic Instability — accumulating damage to DNA over time. 

Telomere Attrition — the shortening of protective caps on chromosomes with each cell division. 

Epigenetic Alterations — changes in how genes are expressed without changes to the DNA sequence itself.

 Loss of Proteostasis — the breakdown of the system that maintains healthy protein production and clearance. 

Disabled Macroautophagy — the declining ability of cells to clean out damaged components.

 Deregulated Nutrient Sensing — the loss of precise cellular responses to nutritional signals. 

Mitochondrial Dysfunction — declining efficiency of the cellular energy production system. 

Cellular Senescence — the accumulation of aged cells that stop dividing but remain within the body and cause inflammation.

 Stem Cell Exhaustion — the declining capacity of stem cells to repair and renew tissues.

 Altered Intercellular Communication — disruption of the signalling systems between cells. 

Chronic Inflammation — persistent low grade inflammation that accelerates tissue damage. 

Dysbiosis — imbalance in the microbial communities, particularly in the gut, that affect overall health.

Each of these is important and each will receive its own Commentary in due course. 

For now the important point is the framework itself: ageing is not a single event but a set of distinct processes, operating simultaneously and interacting with each other, each of which is now understood well enough to be named, studied, and properly addressed.

That is a different picture from the one most people know. It does not promise immortality or the reversal of time. 

What it does offer is more useful — the understanding that how we age is not entirely beyond our influence, and that the choices made across the other Commentaries in this series are not merely lifestyle preferences. They are, in a number of cases, direct interventions in the hallmark processes themselves. 

The connections between sarcopenia and stem cell exhaustion, between diet and deregulated nutrient sensing, between deep sleep and cellular repair, are not coincidental. They are biological.

The next Commentary will take this one step further — into the territory of the individual. Understanding the hallmarks in general is one thing. Understanding which of them is most relevant to your particular biology is another, and  this knowledge is now within reach.

Jack Lack’s Listening Chair is always here, as is your welcome.