Obesity May Accelerate Biological Ageing, Review Finds

People do not all grow older at the same pace. Two people born in the same year may experience physical decline at markedly different rates.

Excess body fat could help explain part of that difference. A new review brings together years of evidence supporting this possibility.

The argument extends beyond familiar concerns about illness. Obesity may hasten the body’s biological ageing process itself.

Researchers at West China Hospital, Sichuan University, carried out the review.

They investigated the close relationship between obesity and ageing, as well as the biological processes the two conditions have in common.

What causes the body to age

Ageing develops gradually as damage accumulates within cells.

Scientists have described roughly a dozen biological hallmarks of ageing, with chronic inflammation and DNA damage among those understood most clearly.

The World Health Organization classifies obesity as a body mass index (BMI) of 30 or above.

Studies indicate that the chance of premature death is typically lowest at a BMI of 20 to 25, before rising as BMI exceeds that range.

Obesity influences many of the biological routes involved in ageing.

For this reason, the review presents obesity as more than a risk factor for age-related disease: it may be a condition that speeds up ageing itself.

Extra fat leaves the body inflamed

Inflammation is supposed to be temporary. It rises when the body suffers injury or infection, then subsides.

With obesity, however, it fails to switch off. Fat tissue becomes crowded with immune cells that continue releasing inflammatory signals.

Macrophages are among these cells, normally acting as cleaners that remove cellular waste. In obese fat tissue, their share rises from around 10 percent of immune cells to more than 40 percent.

This process is known as inflammaging. It also contributes to insulin resistance, in which cells no longer respond properly to the hormone that regulates blood sugar.

Cellular ageing accelerates

DNA is contained within structures known as chromosomes. At the end of each chromosome is a protective cap called a telomere.

Telomeres shorten slightly whenever a cell divides. Once they become too short, the cell either stops dividing or dies.

Obesity appears to make this shortening happen faster. Young people with obesity had telomeres nearly as short as those of much older adults with lower body weight.

The reason remains uncertain. Oxidative stress and inflammation, both frequently associated with obesity, are the leading explanations.

How obesity alters gene activity

Genes may be activated or silenced without any alteration to the DNA sequence itself. Small chemical markers attached to DNA instead regulate gene activity through a process called epigenetics.

These markers change in a predictable pattern as people age. In certain tissues, obesity seems to accelerate those changes.

One study associated a modest increase in liver weight with roughly an extra decade of epigenetic ageing. The same rise was not seen in blood, indicating that the effect varies by tissue.

The relationship may work in both directions. Weight gain can alter these markers, while altered markers may in turn encourage further weight gain.

Obesity weakens cells and repair systems

Excess fat also strains the cell’s energy-producing machinery: the mitochondria, which convert food into usable energy.

Mitochondria in obese tissue generate less energy. They also display damage more commonly linked with older age.

The body’s repair system is affected as well. Stem cells, which serve as replacement parts for dead cells, become fewer and less robust in obesity.

DNA damage also accumulates. Patients with obesity had around twice as much DNA damage in certain blood cells as people of normal weight.

Ageing cells accumulate more quickly

Some damaged cells no longer divide but do not die either. Instead, they remain in tissue and release inflammatory signals.

Known as senescent cells, they build up with age. Obesity seems to hasten their accumulation, particularly in fat tissue.

Their presence is not confined to fat. In mice fed a high-fat diet, these cells also accumulated in the brain and pancreas.

Other research has found that removing them can benefit ageing mice. It is still unclear whether people would experience the same effect.

Obesity disrupts gut bacteria

Trillions of bacteria live in the gut. Their composition helps shape immune function and metabolism throughout the body.

Obesity shifts this balance. Beneficial species become less common and overall diversity declines.

A disrupted gut microbiome becomes more permeable. Bacterial products can then enter the bloodstream and drive low-level inflammation.

The same pattern occurs in typical ageing, giving obesity another potential route through which to accelerate the process.

Losing weight could reverse some damage

There is a more encouraging aspect to the findings. Some age-related changes appear capable of moving in the opposite direction after weight loss.

Calorie restriction and exercise have been linked with longer telomeres.

Greater weight loss was associated with greater increases in telomere length, with the effect increasing alongside the amount lost.

A small number of reports on surgery pointed in the same direction. DNA stability improved in people with severe obesity after weight-loss operations.

This does not amount to a way of turning back time. The review identifies patterns and associations, rather than proving that weight loss reverses ageing.

Obesity drugs could also slow ageing

The researchers also assessed newer obesity medicines. These include drugs now prescribed for weight loss and diabetes, such as semaglutide, tirzepatide and liraglutide.

In laboratory experiments involving simple animals, some of these medicines reduced indicators of ageing. In one study, liraglutide raised the average lifespan of roundworms by about 9 percent.

Orlistat acts by preventing the absorption of some dietary fat. In cell experiments, it also caused certain tumour cells to kill themselves.

None of these findings demonstrates that the drugs slow ageing in humans. Most evidence comes from worms, mice or cells, rather than human patients.

What the findings cannot establish

The authors are cautious about their conclusions. As a review, their paper gathers and evaluates previous research instead of conducting new experiments.

Most of the strongest evidence comes from mice or cells grown in laboratory dishes. Results in humans are mainly associations, which cannot establish that obesity directly causes faster ageing.

The precise molecular sequence is still not known. Maintaining a healthy weight is already recognised as a way to lower disease risk, and this review indicates that it could also affect the speed at which the body ages.