Speed up and slow down the time for the worm
Svetlana Yastrebova, Biomolecule
Old age is the period of life when the probability of dying is maximum. Some protozoa and coelenterates do not have old age, the chance of death does not depend on their age. But for other animal species, it is possible to construct survival curves reflecting the influence of age on the probability of death. Our old acquaintance, the roundworm Caenorhabditis elegans, shows: the course of aging can be slowed down, but the sequence of aging events can hardly be affected in any way. Experiments with mutant worms living in different conditions have shown that the survival curve can lengthen or shorten depending on heredity and external factors, but its shape almost always remains unchanged.
The development cycle of the roundworm Caenorhabditis elegans. L – larval stages. The dotted arrows show an alternative path of development through the larva of the dower form, which is activated in unfavorable environmental conditions. The numbers show the number of days after egg laying. Drawing from the website www.nap.edu , adapted.Many people want to prolong life and avoid some aspects of aging – or at least postpone them for as long as possible [1].
Studies on a wide variety of animals show that it is possible to increase life expectancy by one and a half to two times, as well as to slow down the extinction of mental activity and some other undesirable processes. And yet, in the vast majority of multicellular animals, the probability of death still increases with age, despite all the manipulations. And this means that the vast majority are getting old.
About the happy minority, or rather, about the study of ageless animals (or animals with negligible aging) and long-lived organisms that are not familiar with typical age-dependent diseases, the article "Overcome aging. Part I. Who got the evolutionary jackpot?".
By tradition, it is worth noting that the connection between the chances of dying with the number of years (months, days) lived was noticed not now, but quite a long time ago. The British mathematician Benjamin Gompertz in the 19th century proposed a mathematical model describing the statistics of human mortality depending on age. This model was used by insurance companies to assess risks in life insurance (Fig. 1). According to it, mortality is the sum of two components – independent and age-dependent (this is the Gompertz function). The latter increases exponentially with age and describes the aging of the body.
Figure 1. Gompertz distribution for US residents in 2005. Drawing from the website www.science-of-aging.com .The Gompertz distribution can be constructed for each animal species.
Mortality data can be combined with fertility information, and then survival curves will be obtained. The shape of the survival curve is different for each species. Of course, I would like to change it so that the probability of dying with age does not increase so steeply. Shall we try?
Let's take a small and well–studied organism that does not live long - so that its death does not have to wait for years (no matter how blasphemous it may sound). Let it be the roundworm Caenorhabditis elegans. The genes responsible for the duration of his life are known, as well as the values of environmental parameters (temperature, food composition, etc.) that allow him to live more or less time. There is a system that allows you to monitor worms in a Petri dish and determine whether they are alive or not by the way they move (or do not move) [3]. All that remains is to "play" with the parameters and see how each of them, as well as their combinations, affect the course of aging of C. elegans.
Actually, this is what scientists from Harvard Medical School in Boston (USA) did [4]. They studied mutants with altered hif-1, daf-2, daf-16 and age-1 genes. It is known about all these genes that their mutations lead to lengthening or shortening of life. The effect of some of them is related to temperature. For example, age-1 and daf-2 at a temperature of 20-30 degrees Celsius control the activity of daf-16, the expression of which itself does not depend on temperature. Therefore, certain temperature values will decrease or increase the lifespan of C. elegans. It turned out that at +20 ° C worms live on average 40 times longer than at +34 ° C (Fig. 2).
Figure 2. C. elegans survival rate depending on ambient temperature. The difference between adjacent curves is 2 ° C (the leftmost – worms lived at +34 °C, the rightmost – at +20 ° C). Figure from [4].Of course, a certain role in life expectancy is played by both the food eaten and the amount of the notorious antioxidants.
Since antioxidants usually slow down aging [5], then oxidants should accelerate it. And so it turned out: worms that were constantly added tert-butylhydroperoxide to their food lived less – just like genetic mutants and those who were kept at elevated temperatures.
In addition, C. elegans that were fed "sterilized" food – bacteria killed by ultraviolet radiation – lived longer than those that fed on live microbes.
Of course, a situation where an organism lives in exactly the same conditions all its life is almost impossible in nature, and the longer the lifespan, the more fantastic it seems. So it would be logical to check how the change of external influences affects life expectancy, whether it is possible to reverse the effect of an unfavorable factor. For example, what happens if the worm starts its life at +34 ° C, and then it becomes not so hot – +20 ° C? To be honest, no miracles will happen. The negative impact of high temperature will quickly age C.elegans, and the coolness will not cancel it in any way. Such a worm will live less than its brethren, who were constantly kept at +20 ° C, although longer than those who lived at +34 ° C all the time.
These data, it would seem, are of little value, given that all the listed genetic and environmental factors in relation to Caenorhabditis elegans have already been investigated, and for all it has been shown that they statistically significantly change the lifespan of model organisms. But there was also one important and unexpected feature. When all the obtained survival curves led "to a common denominator" in time, it turned out that they all have the same shape (Fig. 3)! That is, aging may come later or earlier, but it comes one way or another. The function of the dependence of the probability of death on age does not change, but only the coefficient of this function changes [6].
Figure 3. Reduction of all survival curves obtained in experiments to one time scale. Experiments on Caenorhabditis elegans give the variant described in graphs (a), but not (b). Figure from [6].What does this mean in practice?
For worms, this means that aging, apparently, is a chain of events with a strictly programmed sequence, which cannot be changed, you can only delay its onset as a whole. Well, as for human biology, we still need to understand how the data obtained for Caenorhabditis elegans are applicable to mammals in general and to Homo sapiens in particular.
Literaturebiomolecule: "Senile vagaries of nature: why people stop aging, and mice do not have time to live";
- Biomolecule: "Overcome aging. Part I. Who got the evolutionary jackpot?";
- Stroustrup N., Ulmschneider B.E., Nash Z.M., López-Moyado I.F., Apfeld J., Fontana W. (2013). The Caenorhabditis elegans lifespan machine. Nat. Methods. 10, 665–670;
- Stroustrup N., Anthony W.E., Nash Z.M., Gowda V., Gomez A., López-Moyado I.F. et al. (2016). The temporal scaling of Caenorhabditis elegans ageing. Nature. 530, 103–107;
- biomolecule: "Antioxidants against pyelonephritis";
- Pincus Z. (2016). Ageing: a stretch in time. Nature. 530, 37–38.
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08.02.2015