AFR Postdoc: Biology of Ageing – A small protein with big potential

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With her study of processes in RNA, biologist Caroline Heintz has contributed a valuable building block to our understanding of the ageing process.

Both a curse and a blessing: on the one hand, it is thanks to research and medicine that people are living for longer. On the other hand, with rising life expectancy, the risk of age-related diseases such as cancer, metabolic and cardiovascular diseases and dementia also increases. Understanding the ageing process and its molecular causes plays a key role in the prevention and treatment of such diseases.

Little attention previously paid to RNA processes in research

Science has now taken a significant step further in this area thanks to the research of Caroline Heintz. The human biologist at Harvard School of Public Health looked at ‘Pre-mRNA processing and RNA homeostasis in dietary restriction-mediated longevity’ in RNA processes and their role in the ageing process. RNA (ribonucleic acid) comes from genetic material, DNA, and is a kind of blueprint for proteins that perform the actual functions of an organism. The biologist wanted to find out whether increased RNA homoeostasis, i.e. maintaining the state of balance in the organism, eventually leads to longer life.

“We know that changes in DNA and proteins significantly damage cells, which in turn can lead to ageing and ultimately death,” explains Caroline Heintz. However, little attention has been paid to RNA processes and homeostasis in previous research. The biologist has changed this.

In her study, which was financed via the FNR AFR postdoc programme, the scientist looked at the splicing process, a key step in RNA processing (pre-mRNA processing). The researcher also wanted to find out how the condition of RNA helps slow the ageing process as a result of the positive effects of dietary restriction.

Dietary restriction delays the ageing process

“Ever since the 1930s, we have known that dietary restriction without malnutrition leads to a longer lifespan,” says Caroline Heintz.

This applies equally to humans and animals such as rhesus monkeys or mice. And it also applies to worms, which are a recognised laboratory model for scientific research, and which were also used in the Harvard researcher’s study. The biologist compared the RNA molecules of 3- and 15-day-old worms, some of which were fed at will, some of which were subject to dietary restriction.

After 15 days, 25% of the worms that were fed without restriction were dead, whereas those on a restricted diet all remained healthy.

“Data analysis of samples showed that pre-mRNA processing loses efficiency and accuracy during the ageing process,” explains the biologist. “Reduced efficiency leads to splicing errors and defective gene products, which bring cells out of balance and can cause cell damage during ageing,” she adds. In contrast, she identified a significantly younger splicing profile among worms on a restricted diet.

Benefiting from diet without having to fast

In her study, Caroline Heintz was also able to show for the first time, that in the splicing process a specific protein – splicing factor 1 (SFA-1) – is required to slow down the ageing process. And that’s not all. She also found that this protein, when present in higher concentrations, could also extend the lifespan of worms that were not on any diet. As the researcher explains, the success of dietary restriction depends significantly on protein SAF-1.

According to the young researcher, who is currently working on the underlying molecular mechanisms, her work provides basic findings on the ageing process and should help spur further investigations. However, no matter how good dietary restriction is for health, it also has a serious disadvantage, which it shares with all other diets: it is very difficult to stick to over a long period. Caroline Heintz therefore hopes that investigating molecular mechanisms will help develop new methods and active ingredients. This may help imitate the effects of dietary restriction so that fasting is no longer necessary.

This success story originates from the FNR 2017 Annual Report – view the Annual Report as PDF or interactive digital version