Imma Perfetto
Cosmos science journalist
Humans have incredibly variable lifespans, but less than 30% of this natural variance in life expectancy is explained by heritable differences in our genomes.
Researchers are turning to worms (Caenorhabditis elegans), which also have large, natural variation in lifespan, to investigate how ageing is influenced at the molecular level.
A new study of C. elegans traces the origin of this variation to changes in the messenger RNA (mRNA) content in germline cells (sperm and egg cells) and somatic cells (the rest of the body).
Instructions for how to produce proteins are transcribed from DNA into mRNA, which is transported into the protein factory of the cell where its instructions can be translated into protein.
The study found the balance of the amount of mRNA in germline and somatic cells becomes disrupted, or ‘decouples’, over time in the worms. This causes ageing to run faster in some individuals than others.
The magnitude and speed of this decoupling process is influenced by a group of at least 40 genes. The genes are involved in a wide range of functions within the body, from metabolism to the neuroendocrine system.
The researchers found that knocking down some of the genes (stopping their transcription into mRNA) extended a worm’s lifespan, while knocking down others shortened it.
“Whether a worm lives to day 8 or day 20 is down to seemingly random differences in the activity of these genes,” says Matthias Eder, first author of the paper in the journal Cell and researcher at the Centre for Genomic Regulation (CRG) in Spain.
“Some worms appear to be simply lucky, in that they have the right mix of genes activated at the right time.”
Knocking down 3 genes – aexr-1, nlp-28, and mak-1 – had a particularly dramatic effect, reducing the range in lifespan variance from around 8 days to just 4. Rather than prolonging the lives of all worms, silencing any one of these genes drastically increased the life expectancy of worms with shorter lifespans, while the life expectancies of the longest-lived worms remained largely the same.
“This isn’t about creating immortal worms, but rather making ageing a more equitable process than it currently is – a fairer game for all,” says Nick Stroustrup, senior author of the study and group leader at CRG.
“In a way we’ve doing what doctors do, which is take worms that would die sooner than their peers and make them healthier, helping them live closer to their maximum potential life expectancy.
“But we’re doing it by targeting basic biological mechanisms of aging, not just treating sick individuals. It’s essentially making a population more homogeneous and more long lived to boot.”
