Scientific Breakthroughs in Anti Ageing

Advances in science have entailed upon the human race the windfall of increased life expectancy. While the average life span in developed countries have registered an increase of 20 years and pegged at 82 yrs, in India it is 66.4yrs. Long life is a remarkable achievement and society yearns for the same. But long life also puts a burgeoning pressure on the resources and opportunities in developing countries. The real challenge that embodies long life is living better. Hence the real task accompanying the bantam feat is to ensure that an individual should age gracefully, physically fit, mentally sharp and economically secure.

 Extraordinary medical and scientific advances have contributed enormously towards improving the quality of living and subsequently the life expectancy surged. The phenomenon described as technophysio-evolution described by eminent economist Robert Fogel has brought about immense biological changes in the physiology of the human body which was made possible through numerous advances in technology. A steady supply of food grains, discovery of electricity, invention of techniques like refrigeration, pasteurisation, water purification, vaccination has dramatically reduced deaths due to contagious diseases and premature deaths. These changes have brought an increase in body size by over 50 % and improved robustness and capacity of vital organs too. Even our brains have begun to process information much faster. With the availability of technologically advanced devices ageing has been reduced to minor inconvenience.

Scientists have been relentlessly toiling for several decades to crack the code of ageing. Research carried out at the University of Texas Health Science Centre San Antonio, indicated that a mouse fed with rapamycin seemed to age slowly by reducing damage to certain cells. Even the vital organs like heart and liver fed with rapamycin aged very slowly and its nervous system was quite agile and extremely receptive when compared to its peers of the same age. It was devoid of tumours even. Rafamycin diet laced mouse lived 20% longer than unfed ones. Rapamycin is administered to human subjects to prevent organ rejection after transplantation. Rapamycin was obtained from soil samples in 1964 in an expedition to Easter Island. It works on a wide variety of species like yeast, flies, mice and worms and hence convenient for extensive studies.

Rapamycin works by interrupting with the functioning of a gene mTOR, found in mouse and man. mTOR controls the intake of cells and use of energy. It signals cells to absorb more nutrients when food is abundant and taps into other energy related pathways when nutrients are no longer available. It restricts intake of calories and prolongs life. Rapamycin suffers from pit falls too. In mouse it resulted in 30% smaller body size than average. Its regular use is likely to develop cataracts and increases propensity to diabetes. Male mouse tend to experience gradual loss of testicular functioning. Even human patients who took rapamycin after transplantation had higher changes of developing diabetes and risked cataracts. But it still seems to be a promising anti-ageing drug and calibrating the right doses of medication might tip the balance in favour of longevity with minimum risks.

Another well studied scientific pathway was related to dyskeratosis congentia, a condition of telomere dysfunction, wherein rapid shortening of the telomeres or the ends of chromosomes greatly enhanced ageing. Research indicated that if  cells with the disorder are rectified then premature ageing can be averted. Thus, offering a great promise of turning back the clock. Extensive research was done to understand the role played by telomeres. Carol Gredier, who discovered the enzyme telomerase and cracked the puzzle of the telomere replenishment, was awarded a Nobel Prize too.

Scientists of Harvard Stem Cell Institute hit upon an innovative technique in which a young and an old mice are conjoined in a Siamese-twin style to share the same blood system but kept everything else separate rejuvenated the older mice. They exhibited new cell growth in their brains, muscles were stronger and the enlargement of heart which comes with age was reversed. It was found that a protein GD11 abundant in the younger mice and scarce in old mice could have turned the tables in favour of anti-ageing. Further detailed investigations are to be carried out before endorsing the effects of GD11 scientifically.

In the meanwhile Dena Dubal from the University of California suggested that increase levels of the hormone klotho causes mice to live 30% longer. She suggested that nearly 20% of human beings   carry this gene and live on for an extra 3-4 years. These new discoveries added momentum to the research on longevity. Scientists are hopeful that  they can unravel several such strategies that can interrupt ageing.

Longevity research encompasses the idea of delaying ageing or facilitating slower ageing. The central focus of the research is staving off aging. It is not about extending the life indefinitely but prolonging the healthy life for little longer. No one with a fragile health would want to live long. After all, the real joy of living lies in enjoying life to its fullest in the best of physical and mental health.

@ Copyrights reserved.

Self-Organising Tiny Robots: Kilobots

I was simply awed by the sheer intelligence and simplicity when I read about Kilobots. The marvellous, small few centimetres in diameter robots, standing on three pin legs, powered by coin batteries were developed in the laboratory of Professor Radhika Nagpal and Fred Kavali of Harvard School of Engineering and Applied Sciences. A kilo or a swarm of 1024 autonomous robots assemble into two-dimensional pattern formation upon instructions without human intervention. An initial set of instructions are beamed to the robots via infrared following which the robots would work autonomously. Four robots mark out origin of a coordinate system and the remaining will receive a 2-D image they have to mimic. Using primitive behaviour, robots follow the edge of the group, track the distance and maintain a sense of relative position. They take turns in moving towards an acceptable position and assemble into the pre-directed shape. Kilobots communicate with its neighbour through and in built infrared transmitter. They have no sense about their broader outer environment. They can locate the position of their neighbours and their point of origin and are capable of assembling into a shape by gauging the position of its neighbour.

Kilobots are very simple in design and their abilities are variable and less reliable. They are basically designed to carry out collective tasks. Just as trillions of cells that constitute a complex organism communicate with each other and carry out complex tasks. These robots demonstrate how complexity can arise from simple behaviours performed enmasse.

The team basically drew inspiration from biological systems where individuals assemble to carry out tasks. An army of ants by relaying information among themselves construct bridges and rafts to cross difficult terrains. Similarly social amoebae cooperate with each other especially when food is scarce to form a huge fruiting body and escape the harsh external environment. Even the individual cells of cuttlefish change colours to blend into its surroundings. Nagpal has earlier developed a swarm of robots TERMEs inspired by termites but its algorthim for self-assembly wasn’t demonstrated. Kilobots were inspired by the collective functioning of a colony of ants. Till date robot swarms of around 100 were constructed. Kilobots are thus a unique creation wherein coordinated action of tiny 1024 robots is demonstrated.

To cut down the cost of constructing kilobots, certain tradeoffs are made. It has a simple design and moves with two vibrating motors which allows it to slide across a surface on its rigid legs. They have built in infrared receiver and transmitter to communicate with neighbouring robots. It is myopic and has no access to birds-eye view. It can’t move in a straight line as a result its abilities are more variable and less reliable. But the strength of the swarm overcomes individual weaknesses. With the smart algorithms it can overcome its limitations and can complete human-specified tasks of assembling into a particular shape with precision. These robots are capable of correcting mistakes. If they sense traffic jam, robots moves off the course, nearby robots sense the problem and cooperate to fix it.

Kilobots functioning can be represented as a milestone for the computer scientists in the development of collective Artificial Intelligence (AI). The development of kilobots is exemplary due to inherent difficulties of algorithmic limitations on coordinating large numbers and the cost of the labour involved in fabricating such tiny devices. Kilobots are test bed for Artificial intelligence and are manipulated to carry out collective tasks. Increasingly, robots are now required in coordinated tasks like environmental clean-up or disaster relief and for self-driving on highways. The potential for such swarms is huge in construction, agriculture, mining and medicine.

 

 @ Copyrights reserved.

Cracking Protein Folding : Unboiling of an egg

At the first instance, the scientific accomplishment of getting egg protein back intact after boiling or unboiling the egg in short might sound silly and foolish accomplishment. But the seemingly frivolous task of retrieving protein in its original form is the most daunting task. Protein biologists struggle with mind boggling and finicky protein extraction protocols to obtain a functional protein in purest form but the protein becomes unusable as its gets entangled with itself or gets stuck with the containers and instruments during experimentation. Thus significant amount of precious protein is lost. This technique besides revitalising the protein holds the key for cracking the protein folding problem too. It offers a magical solution for refolding the proteins into its original shape.

Proteins are quintessential and the most indispensable tools for working in biological and chemical laboratories. In vivo protein synthesis is carried out ribosomes dictated by the genetic code. Basically proteins are made of amino acids that contain carbon, hydrogen, nitrogen, and sulphur oxygen. Functionality or the efficiency of proteins is determined by the unique nature of folding of proteins. More often the nature of bonding (hydrophilic –water loving or hydrophobic- water hating) between the molecules in the protein determines the shape and activity of the proteins. Proteins in their native state have lowest energy and are most stable.  

Scientists during the course of biological or chemical research lose significant portion of precious proteins as they get stuck to containers, instruments or get entangled with each other becoming unusable. Most often these proteins couldn’t be salvaged easily. Existing techniques are tedious, time consuming and even the amounts of protein retrieved is too low. Scientists at the University of Irvine have claimed to have discovered a technique which can help in untangling the protein and allow them to return to their original conformation.

Gregory Weiss’s lab using a vortex fluid device untangled proteins from the boiled egg. The vortex fluid device was used by an Australian lab to peel sheets of carbon of few atoms thickness from graphene. The device spins molecules in liquid state and spins them through an open- ended test tube. The liquid spreads out as a thin layer of few microns (one millionth of meter) thickness. The forces in the rapidly spinning tube transfer energy to the molecules, separating them in a controlled way. Weiss contemplated on using the machine for revitalising proteins. Egg white is watery containing several proteins besides lysozyme. Upon heating structural bonds between proteins are broken, thus they lose their native conformation and become a thick clump of solid mass. Now, scientists tried to recover lysozyme by dissolving the egg white in a solution that breaks the clumps overnight. After a day the solution becomes clear, full of unfolded proteins.

Refolding is the biggest task to restore the functionality of protein. Solution of unfolded proteins is whirled through the vortex fluid machine wherein proteins spread out as thin layer separated from its neighbour thus allowing the proteins to refold without tangling. By fine-tuning the speed and rotation of the vortex, scientists can generate the force strong enough to separate protein molecules apart from each other and gentle enough to allow them to refold into their natural shapes.  Scientists first used this technique to restore a protein from Escherichia coli, protein kinase A (PKA) three times larger than lysozyme. They slightly modified the protocol to refold the protein. They managed to manipulate the protein into refolding by hinging one end of protein onto a large bead (Ni+2charged immobilised metal affinity chromatography). This in fact is similar to the process by which proteins are folded naturally by the ribosomes.

The force requirement for different protein would vary and subsequently the protocol should be effectively reconstructed to suit to the needs. Scientists are now aiming to build a large-scale vortex machine and exploring the possibility of using different solutions, level of forces and settings suited for different proteins. This method has the ability to transform the production of proteins. Pharmaceutical companies have started creating cancer antibodies in expensive hamster ovary cells which often don’t fold properly and a misfolded protein is not functional. This technique could be of great help to pharmaceutical and biotechnology industries that work on recombinant proteins. It can aid in untangling over expressed proteins that are jettisoned into inclusion bodies as complex aggregates.

@ Copyrights reserved.