A group of genes involved in building components for our cells also impacts our lifespan, according to a study published in the journal Genome Research (1). Researchers already knew that these genes can extend the lifespan of small organisms—including the fruit fly—but, for the first time, this work showed they have an impact on humans as well.
Curiously, the genes have a negative effect: a lower activity means a longer life. The University College London, UK, analysed genetic data from over 11,000 people who lived exceptionally long lives. This data showed that people with low activity for these genes had a higher chance of living longer. What’s more, the team found evidence that the genes have a powerful effect on some internal organs, including the liver and skeletal muscle.
“We have already seen from extensive previous research that inhibiting certain genes involved in making proteins in our cells can extend lifespan in model organisms such as yeast, worms, and flies. However, in humans, loss of function in these genes has been seen to cause diseases, such as developmental disorders known as ribosomopathies,” said Dr. Nazif Alic (UCL Institute of Healthy Ageing) and co-author in this study. “Here, we have found that inhibiting these genes may also increase longevity in people, perhaps because they are most useful early in life before causing problems in late life.”
These genes are involved in making proteins in our cells, which is vital for our survival, but we don’t seem to need them as much later in life. In fact, reducing their activity later in life is associated with an extended lifespan. According to the UCL researchers, this is a case of antagonistic pleiotropy. In simple terms, this means these genes were selected through evolution because they play a vital role in early life, but they end up having a negative impact later in life.
These findings strengthen previous evidence suggesting that some drugs —such as rapamycin— can prolong our lifespan. These drugs inhibit some of the mechanisms where these genes are involved, and in effect, block its activity.
“Ageing research in model organisms, such as flies, and in humans are often separate efforts. Here we are trying to change this. In flies, we can experimentally manipulate ageing genes and investigate mechanisms. But ultimately, we want to understand how ageing works in humans. Bringing the two fields together using methods such as Mendelian Randomisation has the potential to overcome the limitations of both fields,” said Professor Karoline Kuchenbaecker from the UCL Genetics Institute.
(1) Javidnia S, Cranwell S, Mueller S, Selman C, Tullet J, Kuchenbaecker K, Alic N (2022) Mendelian randomization analyses implicate biogenesis of translation machinery in human aging. Genome Research,DOI: 10.1101/gr.275636.121