Fight Aging!

The comparative biology of aging is a field that attempts to use differences between species to better understand the genetic and metabolic roots of longevity. Why do some neighboring species of a similar size, such as mice and naked mole-rats, have such radically different life spans, wherein the mole-rats can live nine times as long? Why are humans very long-lived in comparison to other primates? How is it that individuals in some whale species can live for two centuries or more with a thousand times the cell count of a human and yet not have a thousand times the cancer incidence? On the one hand this is a potentially effective way to seek out the few important parts of a very complicated system, mammalian biology, that is poorly understood in depth at this time. It is a short-cut through the vast unknown. On the other hand, the promise at the end of the day is not just knowledge, but the possibility that perhaps therapies or other beneficial alterations to human biology could be produced as a result of these investigations.

It is hard to say whether it is plausible to hope for cross-species porting of useful features of biochemistry, even between mammals. The devil is in the details, and the details are going to vary widely on a case by case basis. It is very possible that researchers will in the next couple of years uncover a beneficial feature in whales that is clearly and evidently useful, but linked to particulars of their biochemistry in ways that make it absolutely impossible to recreate in humans. The investigations of naked mole-rats are much further along in comparison to of those of whales and are turning up some items that sound plausible to attempt as human therapies and other items that sound near impossible to safely recreate in humans at our presently level of technology. Equally the same job might be a walk in the park for the biotechnology of the 2030s: at this point far too little is known to do more than speculate.

Step one in all of this is to sequence the genome of the species in question - it's hard to get too far into the details without that. You might recall a recent publication on the bowhead whale genome from one of the two teams working separately on that project. Here is an article on the work of the other team, who have put up an online searchable database for those interested in exploring the genome:

Could a 200-year-old whale offer clues to help humans live longer?

Joao Pedro de Magalhaes and his team at the University of Liverpool sequenced the genome of the bowhead whale, the longest living mammal on earth. The team wanted to understand why they live so long and don't succumb to some of the same illnesses as humans do earlier in life. "One of the big mysteries of biology is understanding species differences including species differences in aging. For example, mice age 20 to 30 times faster than human beings and we don't know why ... Even primates which are closely related to us age considerably faster than human beings. There has to be some genetic basis to why humans age slower than chimpanzees for instance which are very genetically very similar to us. Likewise, there has to be some genetic basis as to why bowhead whales live so long and appear protected from diseases."

With a 1,000 times more cells than a human, the whale should have a much higher probability of cell death and disease. It doesn't. In their findings the team found as many as 80 candidate genes that may help protect the whale from cancer or contribute to it being the longest living mammal on earth. The team found that the whales have genes related to DNA repair, as well as those regulating how cells proliferate, that differ from those found in humans.

There is a huge industry searching for that elixir which could help humans live longer. Some research has gone into finding what is called longevity genes that could lead to new drug therapies while other research promotes such things as exercise and healthy eating to extend your life. Two groups which funded most of the whale research - the Life Extension Foundation and the Methuselah Foundation - are seeking that magic potion. Life Extension focuses on such things as hormonal and nutritional supplements to fight aging while Methuselah is heavily invested in tissue engineering and regenerative medicine "to create a world where 90 year olds can be as health as 50 year olds, by 2030."

Methuselah's co-founder and CEO Dave Gobel said it invested in the whale research as part of its "hypothesis that the best way to find out how to become longevity outliers is to study those who already are genetic outliers within mammalian species" and then find "what genetic complexes, pathways seem most common among these outliers and to explore what they do, how they act, and what if any advantages can be derived from them to apply in humans."

The Bowhead Whale Genome Resource

The mechanisms for the longevity and resistance to aging-related diseases of bowhead whales are unknown, but it is clear these animals must possess aging prevention mechanisms. In particular in context of cancer, bowhead whales must have anti-tumour mechanisms, because given their large size and longevity, their cells must have a massively lower chance of developing into cancer when compared to human cells. As such, we sequenced the genome of the bowhead whale to identify longevity assurance mechanisms.

A high-coverage genome assembly, and corresponding annotation, of the bowhead whale is made available to the scientific community to encourage research using data from this exceptionally long-lived species. Overall, this project aims to provide a key resource for studying the bowhead whale and its exceptional longevity and resistance to diseases. By identifying novel maintenance and repair mechanisms we will learn what is the secret for living longer, healthier lives and may be able apply this knowledge to improve human health and preserve human life.

As it is turning out the study of comparative biology over the next decade or so will probably not produce much in the way of practical applications in treating aging, but rather be of relevance to advances in (a) cancer treatment, through what is learned from naked mole-rats and possibly from whales, and (b) regenerative medicine, through investigations of proficient regenerators such as salamanders. Those items are where the money is flowing. That said, this research should lead to faster progress in the scientific goal of fully mapping the process of aging and its interaction with metabolism at the detail level, but as outlined elsewhere at Fight Aging! this is not the road to human rejuvenation. At best, given the field as it stands at present, altering the operation of our metabolism can only aim at modestly slowing the accumulation of cellular and molecular damage, not repairing it or reversing it, and even this will be a vast and complicated undertaking. If we want rejuvenation, we must instead aim at repair of the metabolism we have as the primary objective, and fortunately significant progress towards this goal does not require much more knowledge than we have already.