International Business Department           Liu Bojia           July 02, 2024

  In life, we often see that some people are still hale and hearty in their nineties, while others are already weak and senile in their sixties. Why are people so different from each other? Why do some people age slowly and live long?

  To answer this question, the answer can be written very long, simply put, both inborn genetic factors, but also by the influence of the acquired living environment. So which factors are most influential? Results from twin and family studies have shown that only 30 per cent of the difference in life expectancy between people is caused by genetic differences in the DNA sequence, and the majority - 70 per cent - is not explained by genetic factors.

  In order to explain the difference in aging between humans and humans, the showy cryptic rod nematode, a small worm that itself lives only a short two to three weeks, has recently given scientists important insights.

  Often referred to simply as "nematodes", these small transparent worms share many biological characteristics with humans, and are often used by scientists as a model organism to study aging and longevity. And like humans, their natural lifespan varies greatly from one individual to another.

  In this paper, recently published in Cell, a team of researchers from Spain looked at more than 1,000 nematodes in the lab that were genetically identical but still exhibited individual differences in lifespan under the same rearing environment (including diet, temperature, exposure to acquired pathogens, etc.).

  The researchers collected individual transcriptome data from these nematodes and examined differences in gene expression across individuals by measuring the amount of mRNA molecules in different cells. It was found that within a few days, nearly half of the transcriptome differences occurred in "same-age" individuals as they moved from young to old. By constructing individual transcriptome profiles, the researchers were able to quantify individual differences in aging.

  Further analyses showed that in the same nematode, the total mRNA content of germ cells, which are responsible for reproduction, and somatic cells, which make up the body, are highly correlated, creating an "equilibrium". However, with aging, this mRNA balance between the two types of cells may be disrupted, causing individuals to age more rapidly than others.

  In the paper, the study authors conclude that the imbalance in total mRNA content between germline and soma cells is the greatest source of individual differences in the physiology of aging. And the next set of experiments further traced how gene regulatory networks drive said differences.

  The study authors knocked out different genes in the nematode by means of RNAi, and ultimately screened 40 genes that had a significant effect on germ cell and somatic cell mRNA content. The genes in this group are expressed in a diverse range of locations and are active in different tissue types such as germ cells, muscle, gut, and neuronal cells, with molecular functions including regulation of the cell cycle, endocrine signalling, mitochondrial ATP synthesis, metabolism, and ribosomal function.

  In genetically identical nematodes, there appeared to be random differences in the expression activity of these 40 genes, which ultimately led to individual differences in senescence, allowing some nematodes to live for only one week and others to live for three weeks. In the words of the study authors, the "long-lived" nematodes appear to have been lucky enough to activate the right combination of genes at the right time.

  Interestingly, once one of these genes was knocked out, the effect on nematode lifespan varied from individual to individual, not uniformly extending the lifespan of the nematode, but rather narrowing the lifespan gap between different individuals. And, more often than not, it was the ones with the shortest original lifespans that were lengthened, while the nematodes that had lived longer were barely affected. In the authors' view, this makes ageing "fairer".

  However, exactly how this set of genes interacts, and why knocking them out does not seem to have a negative effect on the health of the nematodes, cannot be answered in the current study. But inspired by the nematode, the researchers plan to look for similar factors affecting the rate of aging and differences in lifespan in mice, which are more closely related to human biology, so that the gap in lifespan can be shortened and everyone has the opportunity to live longer and healthier lives in old age.