A research group from Kumamoto University (Japan) has developed an automated measurement system to assess healthy lifestyles using nematodes (C. elegans). Based on qualitative differences in life, this system can classify numbers of nematodes that are, on average, healthy and long-lived, healthy and die prematurely, and live with prolonged periods of ill health.
Because there are many similarities between the devices that prove longevity C. elegans and humans, the researchers believe will make this system easier to develop drugs and find foods that extend people’s healthy lives.
The concept of “healthy life expectancy” was proposed in 2000 by the World Health Organization (WHO) and is an important indicator of population health. It refers to the average life expectancy excluding the life expectancy of continuing medical or nursing care. However, there is no clear scientific understanding of what constitutes a healthy life in animals or experimental cells. Moreover, the technology for a rational and rapid study of the factors influencing healthy life expectancy has not.
Despite being a very simple animal, C. elegans organs such as nerves, skeletal muscles, and digestive tract are different, and many genes associated with mammalian animals are preserved. It is very useful for advanced study in areas such as genetics and molecular biology.
However, while longitudinal analysis of this nematode provides much useful information, previous longitudinal studies had many limitations including 1) sensitivity to various stimuli at room temperature. , 2) long experimental time required for daily measurement, 3) lack of objectivity. as a result of bias for results to be dependent on experimental methods, and 4) the small number of samples that can be operated at one time making it unsuitable for simultaneous measurement of multiple samples.
The researchers sought to address these issues by developing a new healthy lifespan assessment system that maintained the benefits provided by nematodes. They focused on determining the optimal conditions in a living cell imaging system for automatically measuring nematode survival, such as counting the number of nematodes in a sample, excitation temperature , medium thickness, feeding condition, imaging interval, and survival test method.
This became C. elegans Long-life automated monitoring system (C-LAS), a fully automated lifetime measurement system that can measure a large number of samples non-aggressively (up to 36 samples at present). C-LAS uses translucent images of nematodes to identify those that are moving, meaning they are alive, and those that are not moving, meaning that they are dead.
Next, by using C-LAS to observe C. elegans, the researchers found that nematodes can be classified as one of three possible behavioral states: active state (live), inactive survival state, or inactive (dead) state. They described the period of active behavior as the “healthy longevity” and established a new system they called the C. elegans Healthspan automated monitoring system (C-HAS). Like C-LAS, C-HAS is an automated health and longevity measurement system that can differentiate between live and dead nematodes by periodically passing images.
It is also possible to determine when nematodes are in a state of inactive survival (live but unhealthy) when they are only partially intertwined between images. Using C-HAS, researchers can use these parameters for population analyzes. This type of analysis makes it possible to divide nematodes with the same genetic background into four groups: those with an average longevity, those that are healthy and long-lived, those that are unhealthy and ‘die prematurely, and those with a long period of weakness.
The researchers performed a population-wide analysis of nematode healthy longevity using a combination of C-HAS and a statistical analysis of common nematodes with the same genetic background. They found that about 28% of the population had an average life, about 30% had a long and healthy life, about 35% had a healthy life but died prematurely , and had a long period of weakness at about 7%.
They also found that activity – either genetically or through the administration of the drug metformin – protein kinase-activated AMP (AMPK), which is closely linked to healthy life expectancy, significantly increased the population by longevity. healthy living and reduced the population by long periods. of sensitivity. Metformin is thought to increase healthy life expectancy in humans, and the current study supports this hypothesis. Currently, clinical trials are underway to determine if it is linked to healthy longevity.
It may be a bit unexpected to see nematodes being used to measure healthy lifestyles, but we have already used C-HAS to produce new genes associated with healthy longevity that are not. previously identified. This technology makes it possible to easily scan for genes, drugs, or foods that are related to, or even extend to, healthy human lifestyles with a speed and precision not found when using laboratory animals. We anticipate that C-HAS can be used for drug detection research and in the future detection of healthy foods. We are currently working on the development of C-HAS-AI, which will incorporate in-depth learning into C-HAS to encourage automated analysis. “
Tsuyoshi Shuto, Director of Research, Associate Professor, Kumamoto University
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Magazine Reference:
Nakano, Y., et al. (2020) Long-lived intrapopulation analysis in Caenorhabditis elegans identifies W09D10.4 as an AMPK-related health shortening factor. Journal of Pharmaceutical Sciences. doi.org/10.1016/j.jphs.2020.12.004.