How does ageing work and how can you slow it down?

Ageing is an inevitable biological process in which tissue and organ functions gradually decline. It is caused by molecular changes in DNA and proteins, under the influence of both genetic predisposition and environmental factors. Two major driving forces are the accumulation of waste products from cellular metabolism and increasing DNA damage that builds up over the years.

An important mechanism is 'inflammaging': a state of low-grade, smouldering inflammation that develops in older mammals. This is linked to a weakened cellular self-cleaning system (autophagy), causing damaged proteins and poorly functioning mitochondria (the cell's power plants) to accumulate. This in turn leads to oxidative stress, in which reactive oxygen species damage cells further.

Ageing also disrupts epigenetic information: the chemical 'tags' on DNA and the proteins that package DNA change, the expression of regulatory RNA molecules shifts, and dormant stretches of DNA are incorrectly activated. All of this leads to aberrant gene activation and genomic instability. The good news is that lifespan is largely determined epigenetically and is not fixed purely by genetics. Diet and other lifestyle factors can influence this epigenetic information, which in principle offers potential entry points for interventions.

At the cellular level, DNA repair mechanisms also play a major role. The Base Excision Repair system (BER) corrects common minor DNA lesions, such as oxidative damage. Deficiencies in this system contribute to cancer, inflammation, ageing and neurodegenerative diseases. In addition, NAD+ levels (a substance essential for energy production in cells) decline with age, and this is associated with numerous age-related diseases. Stem cells also become dysregulated: they divide more slowly, causing tissue maintenance to deteriorate, yet excessive division depletes the stem cell reserve.

Regarding slowing ageing: in animal studies, NAD+ precursors (such as NR or NMN, substances the body converts into NAD+) improved metabolism, heart function and brain function, and extended lifespan. In humans the results so far have been modest: oral intake raises NAD+ levels in the blood in a measurable and safe way, with indications of slightly lower blood pressure, a better lipid profile and possible kidney protection. However, the studies are small, the clinical mechanism of action is not fully understood, and large randomised trials are still lacking. Inhibitors of epigenetic enzymes extend lifespan in model organisms, but whether this works in humans has likewise not been demonstrated.

Ageing also affects specific organs and tissues in characteristic ways. In the heart, disruptions in energy metabolism, oxidative stress, epigenetic changes and chronic inflammation collectively contribute to fibrosis (scarring), thickening of the heart muscle and reduced pumping function. In joints, there is an indication that ageing of the joint lining (synovial tissue) accelerates osteoarthritis via immune-mediated inflammation, although this remains an exploratory finding. The complexity of all these processes makes it difficult to develop targeted, effective treatments.