How to Die Young at a Very Old Age or Undo Ageing with Aubrey de Grey
If you attended the Xpomet© Medicinale© last weekend, you probably spotted a very eminent guest from Silicon Valley: Chief Science Officer of SENS Research Foundation and renowned gerontologist Aubrey de Grey PhD. He gave a very insightful talk on Day 1 about Ageing and Wellbeing – Reversing the Trend.
If you missed the talk, here’s a summary of what Aubrey de Grey is trying to do with his ageing research: his goal is not to prolong life per se, his goal is to prolong a healthy lifespan andto keep people healthy for longer, with longevity being a fortunate “side effect” of his scientific endeavours.
“Longevity is a side effect of good health”
Aubrey de Grey approaches ageing from a different angle than others in his field. If for some, ill health is a result of ageing, for de Grey, ageing is a cause of ill health. And flipping the equation around changes things quite dramatically.
But what is ageing? In mechanistic terms, ageing could be defined as a combination of two processes: 1) a life-long process whereby the body damages itself as a consequence of its normal operations, creating changes to its own molecular and cellular structures as an inevitable result of living; and 2) a change in the balance between damage and repair that leads to an accumulation of damage in late life, for example tissue damage that causes us to get sick, both mentally and physically.
In other words, the body is designed to tolerate a certain amount of deleterious changes without significant impact on performance. This is why until middle age or later, people don’t display outward signs of disease or ageing. Ageing is the accumulation of initially harmless but eventually problematic self-inflicted damage: in old age you get a more rapid creation of damage and decreased repair, therefore the balance is tipping towards damage accumulation overall.
Having read as far in the article, you’re likely to ask: what causes the change in the balance between damage and repair? The answer is quite simple: the deleterious change is caused by the damage that has accumulated early in life, throughout life, and even before we were born, damage that we don’t have the genetic capability of repairing. That is the clock of ageing. When that type of damage accumulates, we become less efficient at repairing the types of damage that we were once good at repairing.
The whole discussion of “changes” leads us to a concept that is very hot in gerontology right now: epigenetics. This term basically refers to changes that happen in cells that cause differences in which genes are turned on and which genes are turned off. This includes methylation and modifications to histones (proteins that the DNA is wrapped around), all the way to higher level changes such as the packing of chromosomes.
A lot of things can affect the behaviour of a cell in terms of which proteins to express and which not to express.
Regarding methylation, there is a pattern of methylation that is associated with older age. Steve Horvath, a research scientist and professor at UCLA is known for developing the “epigenetic clock” (or the Horvath aging clock) which is a highly accurate molecular biomarker of ageing. It is so precise that researchers can look at lymphocytes taken from a person and identify the person’s age, give or take four years, with 96% accuracy.
Another thing to keep in mind is that many studies showed that the single most important factor that drives ageing is inflammation. These studies on
centenarians and super centenarians (110 plus) looked at various other biomarkers apart from inflammatory markers: lipid profiles, glucose metabolism, tumour markers, liver function, kidney functio and immuno-senescence (a state where your immune cells are not dividing, they are just sitting there and producing more inflammation). Once all these factors were correlated, the conclusion was rather clear that inflammation, not telomere length, predicts successful ageing.
Chronic inflammation is the single most important factor that drives ageing.
However, inflammation is a double-edged sword. We need inflammation, this is how we survive infection.
Interestingly enough, centenarians have a weak inflammatory response, this is how they managed not to succumb to atherosclerosis or Alzheimer’s at the age of 80 or 90. But a lot of people in this age bracket die of infection. The explanation that de Grey has for this phenomenon is that the people who survive are both genetically lucky (they didn’t get an excessive inflammatory response to age-related problems) and environmentally lucky, in the sense that they didn’t contract any infections. Another hypothesis would be that they had a very strong adaptive immune system that compensated for the weaker environmental response.
All in all, he thinks that it’s not a good idea to take people in the 60 to 70 age bracket and dampen down their pro-inflammatory response. Or bump up their anti-inflammatory response since it amounts to the same thing. It’s a trade-off: you’d be lessening people’s risk of progression to atherosclerosis and Alzheimer’s but you’d also be increasing their risk of dying of pneumonia.
Of course, inflammation is upstream of the processes that damage DNA, proteins, lipids, cell membranes, etc. The inflammation is just the smoke, if you will, so the question to ask would be: what caused the fire in the first place?
Much to anyone’s surprise, the single most important factor in driving the greatest amount of accumulated damage is…breathing! A process that is pretty much non-negotiable. The second one being the transport of sugar. There are many things that contribute to ageing and we’re planning to expand on this subject in a future article.
In conclusion, it’s important to mention that there are limits to what we can do today to delay ageing. However, what we can do today with preventative maintenance is key. Using lifestyle optimisation you are maximising your chances of being around long enough to benefit from medical advances that don’t exist yet. In the near-term, you’re going to feel better anyway.