Longevity Briefs: Could Dietary Fibre Slow Immune Ageing?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Human cells have a replication limit – once they have divided a certain number of times (somewhere between 40 and 60 times, depending on various factors), they enter a state called senescence in which further division is blocked. With age, an increasing number of our T cells – a class of white blood cell involved in mounting a targeted immune response to a specific pathogen – become senescent. Not only are senescent T cells unable to divide, but they also release inflammatory signals and a cocktail of other harmful molecules known as the senescence-associated secretory phenotype (SASP).

T cell senescence degrades the immune system’s ability to respond to pathogens, while also contributing to persistent, low-level inflammation throughout the body that is sometimes called “inflammageing”. This inflammation is thought to be a major driver of some of the most severe age-related diseases, including Alzheimer’s disease and cardiovascular disease. Scientists are working on developing drugs that will selectively kill senescent cells, or at least neutralise the SASP factors they secrete. Here, researchers find that butyrate, a short-chain fatty acid produced by gut bacteria when they break down dietary fibre, could have a similar effect.

The discovery:

Researchers first looked at blood and stool samples of a relatively small group of 80 people from a range of age groups, and found that people over the age of 60 had significantly less butyrate in their faeces than people between the ages of 18 and 37. This wasn’t a new finding, but what was new was the finding that levels of butyrate in the blood also declined with age. This decline was correlated with an increase in the number of senescent T cells.

To investigate whether this relationship might be a causal one, the researchers carried out a series of test tube and animal experiments. They first cultured human T cells in the lab and turned them senescent. When these senescent T cells were then cultured with butyrate, they found that they secreted significantly fewer pro-inflammatory SASP factors. Butyrate seemed to achieve this by reducing DNA damage, protecting the mitochondria (the cell’s power plants) from stress and by suppressing the activity of pathways involved in inflammation.

The researchers then moved to experiments in mice. Aged mice were fed butyrate-rich faecal supernatants (liquid extracts from stool) from young mice. Compared to the control group, this intervention was associated with significantly reduced markers of senescence in T cells, as well as lower levels of IL-6, one of the inflammatory mediators released by senescent cells.

The implications:

This study suggests that butyrate might be able to reduce the release of SASP factors from senescent T cells. While butyrate may not be able to reverse senescence, one of the insidious effects of senescent cells is that the SASP factors they release can damage other cells enough to turn them senescent too. Blocking the production of SASP factors is therefore still helpful for preventing the spread of senescence.

The most significant contributor to butyrate production is the consumption of dietary fibre, followed by the consumption of supplementary fibre in the form of prebiotics like inulin. Consuming certain probiotic supplements containing butyrate-producing bacteria may also be beneficial and is worthy of further research. One limitation of this study acknowledged by the authors is that the concentrations of butyrate used in their experiments may not replicate the concentrations that human T cells would be exposed to in practice. That said, enhancing one’s intake of dietary fibre is very likely to be beneficial regardless of whether it translates to less T cell senescence or not.