Fight Aging!

Species have evolved to exhibit natural variations in life span. Even genetically identical clones exhibit variable life spans. This may because this variation in metabolic processes helps to ensure that at least some individuals are better adapted to the details of the present environment, in a world in which aspects of the local environment do indeed vary over time. Species that did not exhibit this variability in characteristics between individuals would be outcompeted by those that did, sabotaged by environmental changes. Any effects on life span are likely only a side-effect of this specific aspect of the ruthless evolutionary competition for early life reproductive success. Thus, as researchers demonstrate here, it is possible to adjust the expression of specific genes to reduce this natural variation in life span, ensuring that short-lived individuals live longer. Doing so may reduce their ability to thrive in a less comfortable environment, but that remains to be determined.

Researchers observed thousands of genetically identical C. elegans nematode worms living in a controlled environment. Even when diet, temperature and exposure to predators and pathogens are the same for all worms, many individuals continue to live for a longer or shorter period of time than the average. The study traced the primary source of this variation to changes in the mRNA content in germline cells (those involved in reproduction) and somatic cells (the cells forming the body). The mRNA balance between the two types of cells is disrupted, or 'decouples', over time, causing ageing to run faster in some individuals than others. The study also found that the magnitude and speed of the decoupling process is influenced by a group of at least 40 different genes. These genes play many different roles in the body ranging from metabolism to the neuroendocrine system. However, the study is first to show they all interact to make some individuals live longer than others.

Knocking down some of the genes extended a worm's lifespan, while knocking down others shortened it. The findings suggest a surprising possibility: the natural differences seen in ageing worms might reflect randomness in the activity of many different genes, making it look as if individuals have been exposed to knockdowns of many different genes. Knocking down three genes - aexr-1, nlp-28, and mak-1 - had a particularly dramatic effect on lifespan variance, reducing the range from around 8 days to just 4. Rather than prolonging the lives of all individuals uniformly, removing any one of these genes drastically increased the life expectancy of worms on the low end of the spectrum, while the life expectancies of the longest-lived worms remained more or less unchanged. The researchers observed the same effects on healthspan, the period of life spent healthy, rather than simply how long an individual is physically alive. The researchers measured this by studying how long the worms maintain vigorous movement. Knocking down just one of the genes was enough to disproportionately improving healthy ageing in worms on the low end of the healthspan spectrum.

The study doesn't address why knocking down the genes doesn't seem to negatively affect the worm's health. "Several genes could interact to provide built-in redundancy after a certain age. It could also be that the genes aren't needed for individuals living in benign, safe conditions where the worms are kept in the lab. In the harsh environment of the wild, these genes might be more critical for survival. These are just some of the working theories."

Link: https://www.crg.eu/en/news/how-make-ageing-fairer-game-all-wormkind