Mitochondrial transplant a ‘fountain of youth’? Exciting possibility thrown up

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New Delhi | Updated: July 25, 2016 7:04:29 AM

Surprising findings from mitochondrial transplants and smart sutures have pushed medicine’s frontiers recently

Mitochondrial might

One of the fundamentals of high-school biology is “the mitochondrion is the powerhouse of the cell”—the organelle is the actual site where food and oxygen get converted into usable energy. So, any kinks in the make-up of an organism’s mitochondria, and it could just die. Mitochondrial diseases are hereditary and, at present, without any cure. Thus, very few people born with mitochondrial diseases survive into adulthood. What makes matter worse is that the kinks in mitochondria are self-induced—these organelles carry their own genome, separate from the main genome in the nucleus.
Now, mitochondrial DNA is maternally inherited—save the nucleus, fertilisation ‘burns up’ the entire sperm. This means if a woman is suffering from a mitochondrial disease, all her children will have it and her daughters will pass it on. Several countries have been working on mitochondrial donation-a procedure in which a foetus’s main genome comes from the biological parents, but whose mitochondria come from a female donor, called the ‘mitomum’. Usually, the fertilised nucleus from a zygote with faulty mitochondria is transplanted in a enucleated donor ovum in which healthy mitochondria are in situ. While the effects of such mixing are benign, a Nature report suggests the effects of such transplantation could actually be beneficial, regardless of whether a disease was present or not. Rat tests conducted by scientists at the Carlos III Centre for Cardiovascular Research in Madrid found mitochondrial transplants significantly retarded ageing-related muscle deterioration. Test animals showed better blood-insulin stability under starvation than control animals.  Their telomeres—caps at the ends of chromosomes, whose shortening is associated with ageing—kept their length for longer than the test group’s. The modified rats had a higher median age of death than the unmodified ones. While the researchers are unsure of what to make of it, the lead scientist believes it could be that the biochemical cost of mismatched genes forces the cell’s metabolism to compensate in ways that improves its overall health. No one’s calling mitochondrial transplant a ‘fountain of youth’ yet, but the study has for sure thrown up some exciting possibilities.

Fast solution
Given how cancer cells have a much higher rate of metabolism—and thus a higher requirement for nutrients—scientists have always contemplated starving them to kill them off. The problem, so far, has been in avoiding the starvation of healthy cells which can have deleterious effects on the patient. The risk of unintended and harmful starvation is most stark for tumour-infiltrating lymphocytes (TIL)—the production of TILs, the most effective anti-cancer weapon in the body’s arsenal, is dependent on proper nutrition. However, Valter Longo and team, at the University of Southern California, might have just found the right nutritional mix to resolve the dilemma. Tests on mice have returned highly encouraging results, in which tumours are weakened while healthy cells receive the nutrition that they require. Dr Longo first demonstrated the efficacy of starvation as a cancer therapy in 2012. In mice experiments, tumours shrunk by an average of four-fifths the original size when the mice, simultaneously receiving anti-cancer drug doxorubicin, were subject to a significantly reduced diet; in contrast, the mice that received the drug with a normal diet showed only a 50% shrinking of tumours. Replication in humans, the consensus however was, could prove too risky. After continued experiments, Longo et al hit upon a dietary combination that is rich in vitamin D, zinc and fatty acids—that boost TIL performance—while being low in the proteins and simple sugars that the tumour cells need. To test its efficacy, the researchers injected 30 mice with breast-cancer cells. For the first two days, the mice got regular food-25% protein, 17% fat and 58% simple sugars and complex carbs, totaling 3.75 kCal per gram. This was followed by a transition diet, of just 1.88 kCal per gram, for ten mice before switching them to a special diet with 0.5% proteins, 0.5% fat and 99% complex carbs that were of little value to the cancer cells. These 10 were put on the near-starvation diet for three days before the standard diet was reverted to and then the cycle was repeated. A separate set of nine from the original 30 were starved for 60 hours every 10 days but otherwise received their normal diets. The remaining 10 received their normal chow throughout the experiment. Upon the diet regime being terminated, the researchers found that the rodents that had received the special diet and those that had been completely starved periodically had developed tumours two-fifths the size of what was found in those that had been kept on a normal diet. When the experiment was conducted again, only with doxorubicin in the picture, the results were similar to Longo’s 2012 findings. The number of TILs was 70% and 80% higher, respectively, in mice that were given doxorubicin alone and mice that were put on the special diet alone than in mice that were given normal chow and no doxorubicin while the number shot up by 240% in those that received both therapies. The diet suppressed the production of an enzyme called haemeoxygenase-1 that protected the cancer cells from TILs in mice.

Stitchin’ time
Suturing wounds with bare threads could soon become a thing of the past, given Tufts University researchers have developed threads—from basic cotton to new-age synthetic—that have micro-electronic devices, microfluidics and nano-scale sensors embedded in them. The result? Smart stitches—sutures that double up as high-tech diagnostic tools. The threads collect data such as tissue temperature, pH and glucose levels and can even tell the doctor if an infection is imminent. The stitches wirelessly send data to computers or smartphones, letting doctors in on the body’s healing process like never before. Though the smart threads have only been tested on, once again, mice and that too under laboratory conditions, if they are eventually embedded in orthopaedic implants or used in organ transplants, infra-level monitoring would become so much easier. Taking it a notch further, Popular Science, the magazine, says it could even mean a hospital gown relaying your vital parameters to your attending doctor.
sarthak.ray@expressindia.com

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