Researchers are exploring the reasons why some individuals live longer than others, with genetic differences playing a significant role in influencing lifespan variation. However, genome sequence alone does not fully explain the natural variance of human life expectancy, prompting scientists to investigate ageing at a molecular level to understand this phenomenon better. Studying ageing in humans is challenging due to the scale and quality of data required, leading researchers to turn to worms, specifically Caenorhabditis elegans, which share biological similarities with humans and exhibit natural variation in lifespan.
A study conducted by the Centre for Genomic Regulation (CRG) observed thousands of genetically identical worms living in a controlled environment, with varying lifespans despite identical environmental conditions. The research identified changes in mRNA content in germline cells and somatic cells as the primary source of lifespan variation, indicating that the mRNA balance between these cell types becomes disrupted over time. This disruption causes ageing to progress at different rates in different individuals, ultimately affecting their lifespan. The study, published in Cell, revealed that a group of at least 40 different genes influence the decoupling process, interacting to determine individual lifespans.
Experiments involving knocking down certain genes, such as aexr-1, nlp-28, and mak-1, showed dramatic effects on lifespan variance among the worms. Removing one of these genes significantly increased the life expectancy of worms with shorter lifespans, while having minimal impact on the lifespan of longer-lived worms. This led to an increase in healthy ageing, measured by the period of life spent in vigorous movement, for worms at the lower end of the healthspan spectrum. The researchers aimed to make ageing a fairer process for all individuals, promoting healthier and longer lives by targeting basic biological mechanisms of ageing.
However, the study did not provide a clear explanation as to why knocking down these genes did not negatively affect the worms’ health. The possibility of built-in redundancy provided by several genes or their non-essential role in benign laboratory conditions compared to the wild environment are among the working theories proposed by the researchers. The study utilized a method that measures RNA molecules in different cells and tissues, combined with the Lifespan Machine, a device that monitors the entire lives of thousands of nematodes simultaneously. The researchers plan to develop a similar machine to investigate the molecular causes of ageing in mice, which have biological similarities to humans.
The findings of this study highlight the complexity of ageing and lifespan variation, showing that multiple genes interact to influence individual lifespans and healthspans in worms. By targeting specific genes, researchers were able to improve the healthy ageing process for worms with shorter lifespans, ultimately creating a more equitable environment for all individuals. The study emphasizes the importance of understanding the molecular mechanisms of ageing to potentially enhance lifespan and healthspan in various organisms, with potential implications for human health and longevity going forward. Further research using new technologies and model organisms could provide valuable insights into the ageing process and potential interventions for promoting healthy ageing.
