Book 2 Listening (1108796), страница 22
Текст из файла (страница 22)
It would be even better, though, if rather than having stemcells transplanted into it, a degenerate organ could be persuaded to repair itself. Until now,no one has managed to do this. But Clare Blackburn of Edinburgh University in Britain, andher colleagues, have succeeded. As they report in Development, they have treated, in mice,an organ called the thymus, a part of the immune system that runs down in old age. Insteadof adding stem cells they have stimulated their animals’ thymuses to make more of a proteinknown as FOXN1. This is a transcription factor (a molecular switch that activates genes), andfor the thymus it turns out to be an elixir of life.The thymus is the place where the immune system’s T-cells mature.
T-cells havevarious jobs, such as destroying body cells infected with viruses. As an animal grows older,its thymus shrinks and the organ’s internal structure changes. As a result, the supply of newT-cells diminishes. That is why elderly people are more subject than the young to infection.Dr Blackburn knew from earlier experiments that FOXN1 is important for the embryonicdevelopment of the thymus, so she wondered if it might be used to rejuvenate the organ inolder animals. To this end, she and her colleagues bred a special strain of mice whoseFOXN1 production could be stimulated specifically in the thymus by tamoxifen, a drug morefamiliar as a treatment for breast cancer.Wild mice are normally killed by predators before they are a year old, but cosseteddomestic versions often make it to two or even three, so Dr Blackburn and her team did theirexperiments on year-old and two year-old animals, as being roughly equivalent to middleaged and elderly humans.
In year-olds, stimulating FOXN1 production in the thymus causedit to become 2.7 times bigger within a month. In two-year-olds the increase was 2.6 times.Moreover, when the researchers studied the enlarged thymuses microscopically, andcompared them with those from untreated control animals of the same ages, they found thatthe organs’ internal structures had reverted to their youthful nature. Most important of all, theyfound, the density of relevant T-cells in the experimental animals’ lymph was twice that of thecontrols.This is not a model for a medical treatment.
Dr Blackburn relied on specially bred micefor the study. FOXN1 is not naturally sensitive to tamoxifen. But this work does provide anopening for regenerative medicine to exploit because it shows that, in the case of the thymus,stimulating production of a single transcription factor can have an astonishing effect—bigger,certainly, than anything yet seen using stem cells. Whether something similar applies to anyother organ remains to be investigated. But Dr Blackburn’s study suggests it might be worthlooking. (From The Economist, April 12, 2014)Script 45.
AgeingForever young?A way to counteract part of the process of growing oldBIOLOGISTS have made a lot of progress in understanding ageing. They have not,however, been able to do much about slowing it down. Particular versions of certain geneshave been shown to prolong life, but that is no help to those who do not have them. A pieceof work reported in this week's Nature by Darren Baker of the Mayo Clinic, in Minnesota,though, describes an extraordinary result that points to a way the process might beameliorated.78Dr Baker has shown - in mice, at least - that ageing body cells not only sufferthemselves, but also have adverse effects on otherwise healthy cells around them.
Moresignificantly, he has shown that if such ageing cells are selectively destroyed, these adverseeffects go away. The story starts with an observation, made a few years ago, that senescentcells often produce a molecule called P161NK4A. Most body cells have an upper limit on thenumber of times they can divide-and thus multiply in number. P161NK4A is part of the controlmechanism that brings cell division to a halt when this limit is reached.The Hayflick limit, as the upper bound is known (after Leonard Hayflick, the biologistwho discovered it), is believed to be an anticancer mechanism. It provides a backstop thatprevents a runaway cell line from reproducing indefinitely, and thus becoming a tumour.
Thelimit varies from species to species-in humans, it is about 60 divisions - and its size iscorrelated with the lifespan of the animal concerned. Hayflick-limited cells thus accumulate asan animal ages, and many biologists believe they are one of the things which controlmaximum lifespan. Dr Baker's experiment suggests this is correct.Age shall not weary themDr Baker genetically engineered a group of mice that were already quite unusual. Theyhad a condition called progeria, meaning that they aged much more rapidly than normalmice. (A few unfortunate humans suffer from a similar condition.) The extra tweak he addedto the DNA of these mice was a way of killing cells that produce P161NK4A. He did this byinserting into the animals' DNA, near the gene for P161NK4A, a second gene that was,because of this proximity, controlled by the same genetic switch.
This second gene, activatedwhenever the gene for Pl61NK4A was active, produced a protein that was harmless in itself,but which could be made deadly by the presence of a particular drug. Giving a mouse thisdrug, then, would kill cells which had reached their Hayflick limits while leaving other cellsuntouched.
Dr Baker raised his mice, administered the drug, and watched.The results were spectacular. Mice given the drug every three days from birth sufferedfar less age-related body-wasting than those which were not. They lost less fatty tissue. Theirmuscles remained plump (and effective, too, according to treadmill tests).
And they did notsuffer cataracts of the eye. They did, though, continue to experience age-related problems intissues that do not produce P161NK4A as they get old. In particular, their hearts and bloodvessels aged normally (or, rather, what passes for normally in mice with progeria).For that reason, since heart failure is the main cause of death in such mice, their lifespans were not extended. The drug, Dr Baker found, produced some benefit even if it wasadministered to a mouse only later in life. Though it could not clear cataracts that had alreadyformed, it partly reversed muscle-wasting and fatty-tissue loss.
Such mice were thus healthierthan their untreated confreres.Analysis of tissue from mice killed during the course of the experiment showed that thedrug was having its intended effect. Cells producing P161NK4A were killed and cleared awayas they appeared. Dr Baker's results therefore support the previously untested hypothesisthat not only do cells which are at the Hayflick limit stop working well themselves, they alsohave malign effects (presumably through chemicals they secrete) on their otherwise healthyneighbours.Regardless of the biochemical details, the most intriguing thing Dr Baker's resultprovides is a new way of thinking about how to slow the process of ageing-and one thatworks with the grain of nature, rather than against it. Existing lines of inquiry into prolonginglifespan are based either on removing the Hayflick limit, which would have all sorts ofuntoward consequences, or suppressing production of the oxidative chemicals that arebelieved to cause much of the cellular damage which is bracketed together and labelled assenescence.But these chemicals are a by-product of the metabolic activity that powers the body.
If 4billion years of natural selection have not dealt with them it suggests that suppressing themmay have worse consequences than not suppressing them. By contrast, actually eliminatingsenescent cells may be a logical extension of the process of shutting them down (they79certainly cannot cause cancer if they are dead), and thus may not have adverseconsequences.It is not an elixir of life, for eventually the body will run out of cells, as more and more ofthem reach their Hayflick limits.
But it could be a way of providing a healthier and more robustold age than people currently enjoy. Genetically engineering people in the way that Dr Bakerengineered his mice is obviously out of the question for the foreseeable future. But if someother means of clearing cells rich in P161NK4A from the body could be found, it might havethe desired effect. The wasting and weakening of the tissues that accompanies senescencewould be a thing of the past, and old age could then truly become ripe. (From The Economist,November 5, 2011)80Unit 15.
FoodScript 46. Diet and the evolution of the brainFish and no chipsThe wonders of docosahexaenoic acidTo pin one big evolutionary shift on a particular molecule is ambitious. To pin two on it istruly audacious. Yet doing so was just one of the ideas floating around at "A Celebration ofDHA" in London this week.
The celebration in question was a scientific meeting, rather than afestival. It was definitely, however, a love-in. It was held on May 26th and 27th at the RoyalSociety of Medicine to discuss the many virtues of docosahexaenoic acid, the most importantof that fashionable class of dietary chemicals, the omega-3 fatty acids.DHA is a component of brains, particularly the synaptic junctions between nerve cells,and its displacement from modern diets by the omega-6 acids in cooking oils such as soya,maize and rape is a cause of worry. Many researchers think this shift and the change in brainchemistry that it causes explains the growth in recent times of depression, manic-depression,memory loss, schizophrenia and attention-deficit disorder. It may also be responsible forriising levels of obesity and thus the heart disease which often accompanies beingoverweight.Michael Crawford, a researcher at the Institute of Brain Chemistry and Human Nutritionin London, believes, however, that DHA is even more important than that.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
