The Peter Pan protein
(appeared in Nov 2019)

(link to main website)

Could the fountain of youth be at hand? asks S.Ananthanarayanan.

It is the process of change, and growing old, that makes us aware of the passage of time. And without the awareness of time, human development, science, art and civilization would have been different.

In a paper in the Proceedings of the National Academy of Sciences (PNAS), Jiarui Song, Dhenugen Logeswaran, Claudia Castillo-González, Yang Li, Sreyashree Bose, Behailu Aklilu, Zeyang Ma, Alexander Polkhovskiy, Julian J.-L. Chen, and Dorothy E. Shippen, from A&M University, Texas, , Arizona State University, China Agricultural University, Beijing and Skolkovo Institute of Science and Technology, Moscow, report a step forward in understanding the mechanism of aging of living things

The step of understanding is about a component of the DNA of cells, which plays a role in making it possible for cells of living things to divide and renew themselves. This component was first discovered in algae in stagnant water and has been found to be there in the DNA of most living things. And the team writing in PNAS has unraveled a part of how it works in the case of plants. As the longest lived things on the planet are plants, the understanding may help find a way to extend human life too!

Growth and reproduction happen as a result of cell division, where a living cell splits, to become two cells that are just like the original cell. The copying takes place thanks to the DNA molecule in the nucleus of the cell, a long, chain molecule, which carries both the blueprint for the construction of the cell and a means by which it can replicate itself. The replication is possible because the DNA consists of a pair of complementary strands

When the two strands separate, each one can draw the elements of its partner strand from the surroundings and regenerate the original.

A problem with the affinity of the parts of the DNA strands to form chemical combinations, which enables replication, is that the strands could get elongated, or that a DNA could form a link with another DNA. The result of such events would be that there could be no viable daughter cell and division would not work. The DNA has thus evolved to have a specific form at its extremities, to mark and announce the end of the molecule, and the DNA itself contains the machinery for the generation of the extremity form.

The extremity form, called the telomere, is a series of repeats of the units of which the DNA is built, And the telomere is formed is with the help of an enzyme, or an agent that promotes the chemistry in living things, called telomerase, which contains the template to build the series of units in the telomere.

An early discovery about the nature of aging, however, was that there is limit to the number of times a cell could replicate itself. The reason was later found to be that at each replication, the daughter DNA was not the same as the parent DNA, but there was a shortening of the telomere. After a series of replications, the telomere ceased to be effective and so was the process of cell division. Cell growth was hence retarded, functions of the organism began to fail and the organism was said to be aging.

Fortunately, Blackburn, Greider and Szostak, who made the discovery in the 1980 (and received the Nobel Prize in 2009), also discovered an enzyme, telomerase, which has the capacity or retard, or even reverse the breakdown of telomere. Telomerase contains the template that enables the synthesis, from the surroundings, of the specific DNA segments that make up the telomere. Alternately, telomerase provides a platform that allows the enzymes that promote the building of the DNA to copy the full length, without missing the end portion, and hence maintain the health of the reproducing cell.

The action of telomere and telomerase are now seen as central to the processes of cell death or cell proliferation. As the large part of an organism’s cells do not replicate a great many times, most cells are not effected by telomere attrition. This, however, is not true of stem cells, which replace cells that are destroyed, continuously, by injury or disease. These become less effective with increasing age, and the organism is less capable of recovering from injury or illness. In fact there are a number of diseases, anemia, diseases of the skin and respiration, which are caused by defects or telomerase.

While finding ways to promote telomerase may thus appear like a solution to the problems of aging, it is seen that enhanced levels of telomerase can have the reverse effect of allowing cancerous cells to replicate without hindrance. Understanding the mechanism of telomerase action is thus important to design therapies that can work without adverse side effects.

The authors of the paper in PNAS note that although the telomerase function is the same over most living species, this is not true of the operative component of telomerase, the part which helps DNA synthesise the telomere during cell division. Discovering the nature of this component, called the telomerase RNA, or TR, has been challenging, the authors say, as the structure and working of TR differs widely over the species, ranging from single celled creatures in ponds to vertebrates.

The team went about the quest by experiment and analysis of telomerase in cells of the plant, Arabidopsis thaliana, a model plant species. The study, the paper says, revealed that despite the variability of the TR molecule, there were two specific structures within TR molecules which remained the same over species. The current study has improved over earlier studies and identified a form of TR, in Arabidopsis thaliana, which can help maintain telomere and also combine with a subunit of telomerase to reconstitute telomerase activity.

The study has also revealed comparable features in the TR in plant cells with that of single celled pond scum and of vertebrates. These suggest an evolutionary route that was followed in the progress from single celled creatures to plants to more complex life forms could be traced, for greater understanding of how persistence of telomere could be promoted or blocked

The process of telomere attrition, which is necessary to prevent uncontrolled cell proliferation, is the reason that living things must age and die. Animal lifetimes are thus rarely longer than a few decades. Bristlecone pines and the Yew trees, on the other hand, live for thousands of years. Understanding how the plant world deals with aging may show us a way extend the human lifetime, or the quality of life, at any rate.


If aging were ovecome

Peter Pan, a character created by the Scottish playwright J M Barrie, is an impish, young boy who has the gift of flight and never grows old. His adventures take place in Never Never Land, a name that implies that things are timeless.

But many aspects of our world would change if such a thing were possible. The need to overcome and discover, the nature of relationships and property, the fabric of society as we know it, depend on the fact that things age and people die. So also the need to procreate, the wonder of renovation and the hopefulness of a second chance

It would appear that immortality is contrary to nature’s law

Do respond to :