One of the holy grails in medicine is improving our longevity. I have made the point for a number of years that we should be focusing more on health span rather than lifespan. There is no point surviving an extra 20 years if you are living in the misery of a serious chronic illness, in constant pain or are desperately unhappy. I am a great believer in prolonging everyone’s life but no one’s death.
Over the past few decades, there have been a number of suggestions of interventions to prolong life. For the last half century, it has been proven and well-known that calorie restriction does extend the life of various animals. This has been proven in a variety of worms, rats and monkeys but has never been proven in human beings.
A number of years ago, Prof Roy Walford wrote the book “The 120 year diet”, where he suggested if you followed his diet of 1500 calories a day of plant food with no meat, no alcohol or coffee, you would live until you are 120. He had a small but loyal group of followers around the world known as calorie restrictors. They didn’t have an ounce of body fat, felt constantly cold, tired, miserable & often depressed but existed under the delusion that they would live to 120. The average age of death in our society is around 80 for a male and 84 for a female. I’d like to report that tragically a few years back Prof Walford died at the ripe old age of 79.
Over the past decade there has been seminal research, especially by Professor David Sinclair at Harvard University, looking at the anti-ageing properties of resveratrol and more recently the benefits of nicotinamide, one version of vitamin B3, with some rather exciting results in laboratory animals. Again, this has not been proven in human beings because of the difficulty of performing a randomised controlled, long-term study of ageing over many years in a number of people.
There has also been some interesting work around the drug rapamycin, which comes from a bacterium found in the soil at Easter Island. Rapamycin affects a molecular pathway known as M-tor and again has been shown to prolong life in laboratory animals.
Two fascinating pieces of research have just been released around ageing. The first revisited the calorie restriction concept in mice & monkeys finding that the reason calorie restriction appears to prolong life is through a direct effect on a process known as DNA methylation. The study reduced calorie intake by between 30–40% in young mice and in middle age monkeys with both interventions showing significant improvements in methylation with age.
Possibly even more interesting was a study recently published in the journal “Genes and Development” looking at a vital body process known as autophagy. Autophagy is a mechanism that clears out used and damaged proteins to be recycled, creating new products for cellular use.
It appears that autophagy promotes health and fitness in the young but drives the process of ageing later in life. The theory of evolution has demonstrated that natural selection results in the fittest individuals being able to pass on their healthy genes. The more beneficial a trait is at promoting reproductive success, the stronger the chance that the trait is passed on to the offspring. Interestingly, once you have survived your reproductive years then the traits that were beneficial for fitness and reproduction may have a paradoxical effect on promoting ageing.
One of the lead authors of the paper Jonathan Byrne stated that ageing is a revolutionary oversight. In this particular paper he found 30 genes that demonstrated this paradox by only examining 0.05% of the genes in a particular worm known as C. elegans.
The genes that are involved in regulating autophagy, maintaining fitness and reproductive ability in the young, tend to accelerate the ageing process. These genes are essential for young ones to reach maturity but after reproduction they tend to malfunction with age.
This is where it becomes very interesting in that it appears to be better to switch off the autophagy genes in the regulator neurones of worms completely than allow them to rundown to the point where they are defective and promote ageing.
When the researchers switched off the autophagy genes in the ageing worms they prolonged their life by 50% but also their cells functioned better and more efficiently.
Although these benefits to human beings are still a long way off, if we can find a mechanism to switch off autophagy in our neurones as we age, this could be a major key to longevity.
As the iconic comedian Woody Allen once said, “it’s not that I’m afraid of death it’s just that I don’t want to be there when it happens”. A survey was once done on a group of 20 year olds asking them how long they would like to live. The average answer was around 70 years old. When the same survey was given to a group of 79 year-olds, they were happy for as long as they could be given. When you hear the “wings of the angel of death flapping around your ears” you certainly want to maintain your existence for as long as possible if, of course, your existence is enjoyable and viable. It will be very interesting to see where all this research takes us and sadly, the elephant in the room of overpopulation is a topic for another discussion.