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Have We Found the Key for Longevity in Humans?

A crucial protein which is responsible for longevity has been identified for the first time in monkeys


 

 

Plethora of research is happening in the field of ageing as it is absolutely essential to understand the genetic basis of ageing to be able to comprehend how to delay ageing and treat age-related diseases. Scientists had discovered a protein called SIRT6 which is seen to control ageing in rodents. It’s possible that this could also affect development in nonhuman primates. In 1999, Sirtuin family of genes and their homologous proteins including SIRT6 was linked with longevity in yeast and later in 2012 SIRT6 protein was seen to be involved in regulation of ageing and longevity in mice as deficiency of this protein led to characteristics associated with accelerated ageing like spinal curvature, colitis etc.

Using a model which is evolutionarily similar to human, like another primate, can fill the gap and guide us about the relevance of research findings to humans. A recent study published in Nature is the first ever work on understanding the role of SIRT6 in regulating development and lifespan in advanced mammals like primates1. Scientists from China bioengineered world’s first primates’ macaques (monkeys) lacking their SIRT6 protein producing gene by using CRISPR-Cas9-based gene editing technology and experiments so that they could directly observe the effect of SIRT6 deficiency in primates. A total of 48 ‘developed’ embryos were implanted in 12 surrogate mother monkeys out of which four became pregnant and three gave birth to baby monkeys as one got aborted. Baby macaques which lack this protein died within hours of birth in contrast to mice which start showing ‘premature’ ageing in about two-three weeks of birth. And unlike mice, SIRT6 protein is seen to play a crucial role in embryonic development in monkeys because absence of SIRT6 caused serious full body developmental delays and defects. The three new-born babies showed lower bone density, smaller brain, immature intestines and muscle.

Baby monkeys exhibited serious prenatal development retardation leading to serious birth defects caused by delayed cell growth e.g. in brain, muscle and other organ tissues. If a similar effect would be seen in humans then a human foetus would not grow more than five months though it will complete the stipulated none months inside mother’s womb. This would be due to loss of function in SIRT6-producing gene in the human foetus causing it to grow inadequately or die. Same team of scientists have shown earlier that SIRT6 deficiency in human neural stem cells can affect proper transformation into neurons. The new study bolsters that SIRT6 protein is a likely candidate for being a ‘human longevity protein’ and could be responsible for regulating human development and life span.

This study has opened up new frontiers for understanding human longevity proteins in the future. Discovery of crucial proteins can throw light on human development and ageing and direct treatment design for developmental delays, age-related disorders and metabolic disease in humans. This study is already done in monkey, so there is hope that similar studies on humans can shed light on important longevity proteins.

Ageing remains an enigma and mystery for mankind. Research on ageing has been often discussed much more than any other area because of the importance given to youth in society and culture. Another study2 published in Science showed that there may not even be a natural limit for longevity in humans. Scientists from University of Roma Tre in Italy have performed a statistical analysis on the possibilities for survival in around 4000 elderly people who were between 105 years and older and stated that at the age of 105 a ‘mortality plateau’ is reached which means no limit to longevity now exists and after this age the possibility of life and death is at 50:50 i.e. someone could just live much longer hypothetically speaking. It is believed by medical experts that risk of death increases from adulthood till the age of 80 or so. Very less knowledge is available about what happens after 90s and 100s. This study says that human lifespan may not have any upper threshold! Interestingly, Italy is one of the countries having highest number of centenarians per capita in the world so it’s a perfect location, however, to generalize the study further work is needed. This is the best evidence for age mortality plateaus in humans as very interesting patterns emerged. Scientists want to understand the concept of levelling in detail and it seems after one crosses 90s and 100, our body’s cells may reach a point where repair mechanisms in our body can offset the further damage in our cells. Maybe such a mortality plateau could even stall death at any age? There is no immediate answer and many experts state that this study is serious overreaching and biologically implausible as the human body is designed in such a way that it will have its own limitations and boundaries. Many cells in our body do not replicate or multiple after forming the first time around - example in brain and heart - so these cells will die in the ageing process.

Source:

1 Weiqi Zhang et al. 2018, ‘SIRT6 deficiency results in developmental retardation in cynomolgus monkeys’, Nature, vol. 560, DOI: https://doi.org/10.1038/d41586-018-05970-9
2 Elisabetta Barbi et al. 2018, ‘The plateau of human mortality: Demography of longevity pioneers’, Science, vol. 360, no.6396, DOI: https://doi.org/10.1126/science.aat3119

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Vol.1 Issue 10 October 2018

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