Many engineering graduates leave the field for alternative careers, but what they don’t leave is the confidence that any problem has a solution, even if it wasn’t found yet and even if one does not understand all the details.
This is the reason for which one engineer changed gerontology – his name is Aubrey de Grey and he left the field of artificial intelligence research to do his PhD in gerontology. While the seniors in the field spent days trying to understand the minutiae in the aging process, he came up with seven strategies for repairing aging damage in humans with the technology and understanding we have right now – the 7 strategies were unified in the SENS project, currently a non-profit research foundation.
The project was a welcome approach to the stale gerontology world. As my geriatrics and gerontology mentor likes to say, our patients’ lifespan increased thanks to the progresses in geriatrics, not because of a better understanding of aging. Indeed, outside calorie restriction I can’t think of any other practical application of gerontology (but please contradict me here!) that we currently use in living people. This is why Aubrey de Grey (besides Caleb E. Finch, the first researcher bringing forward the concept of negligible senescence) is my hero in gerontology.
According to the SENS creator, the main types of aging damage – and the corresponding solving strategies – are:
1. Mitochondrial mutations – MitoSENS
2. Intracellular junk – LysoSENS
3. Extracellular junk – AmyloSENS
4. Extracellular crosslinks – GlycoSENS
5. Cell senescence – ApoptoSENS
6. Cell loss and atrophy – RepleniSENS
7. Cancer-causing nuclear (epi)mutations – OncoSENS
As much as I can think of, I can’t come up with any other aging damage seen in my patients and since geriatrics is often considered a specialty of accurate diagnoses with no actual treatments, I am more than open to the development of all these strategies.
As a geriatrician I can improve the quality of life of my patients and sometimes even prolong their lives, but what I can’t currently do is turn back the damage they incurred over years and years of life.
Although the species that already escape senescence do this through other mechanisms (see the articles here, here and here), understanding each of the SENS strategies is the purpose of the current series. The underlining assumption is that the study of negligible senescence in other species and the Strategies of Engineered Negligible Senescence can positively influence each other and bring rejuvenation to people one day.
So let’s start with the first such strategy depicted as:
MITOSENS
What are mitochondria?
Mitochondria are tiny cell organelles whose main task is to produce ATP – the energy currency of life.
They do that by aerobic respiration – burning glucose in the presence of oxygen.
Mitochondria are responsible for most of our energy needs – the aerobic ones at least – and they allowed the development of complex, energy-demanding organisms like us.
What happens to them as we age?
Mitochondria are synthesized by genes located in:
-the nucleus
AND
-the mitochondria themselves
The mitochondrial DNA – which in humans encodes 13 different proteins – is inherited from the mother only. Another of its peculiarities is that it is circular – just like in bacteria.
The problem is that all these genes must be kept intact in an environment not conducive to preservation: mitochondria themselves produce unstable molecules called “free radicals” while doing their regular job.
What happens to a mitochondrion that is mutated?
If the rate of mutations is so high that the organelle can’t produce energy anymore, then the lysosomes (other important organelles over which we’ll talk further) tag them for recycling. In this sense, the lysosome is the mitochondria’s “predator”.
Are there cases when the lysosome can’t tag a mutant mitochondrion?
The clonal expansion hypothesis (presented by Dr. Aubrey de Grey in his book “Ending aging”) mentions that mutant mitochondria have a part of their DNA deleted. Since the power plant is now effectively shut down – not merely failing to accomplish its duties appropriately -, the lysosome is not able to tag it.
These mutant mitochondria survive, releasing a surplus of electrons outside the cell.
Oxygen easily accepts surplus electrons and the cell containing such mutant mitochondria outputs an increased number of free radicals.
Some of these cells’ toxicity may be a cause of LDL oxidation and probably other free-flowing substances in our bodies. Atherosclerosis becomes rampant as we age.
What is the solution proposed to this problem?
The solution proposed by Dr. Aubrey de Grey is to move the 13 mitochondrial genes into the nucleus.
How can we test this strategy in humans?
Just like the rest of the SENS strategies, accomplishing this task will first be accomplished in diseases which share a common mechanism to one or several types of aging damage – aging is not officially recognized as a disease, so such bypasses are necessary to progress the field. In the case of MitoSENS, one such group of disorders are the mitochondriopathies – a group of rare genetic disorders where people inherit mitochondrial mutations rather than develop them in the course of a normal lifespan.
So this is the plan for MitoSENS, but that’s not all that needs to be done. As we age our housekeeping is done less frequently and less efficiently – during the next article, we will see what happens inside cells when we fail to remove wastes appropriately!
Bibliography:
“Ending aging” by Aubrey de Grey (link)
Anca Ioviţă is the author of Eat Less Live Longer: Your Practical Guide to Calorie Restriction with Optimal Nutrition available on Amazon and several other places. If you enjoyed this article, don’t forget to sign up to receive updates on her second book regarding a comparative biography of aging from the simplest to the most complex organisms known.
“Although the species that already escape senescence do this through other mechanisms (see the articles here, here and here) […]”
— then perhaps you could suggest to the SENS researchers the ideas that you have discovered? (you probably have already thought of that)
From what I’ve noticed, SENS researchers are not interested in comparative gerontology or long-lived species because most of them are very simple organisms and presumably they are not applicable to human beings. SENS researchers are also more interested in repairing the damage of aging than in understanding the mechanisms of aging.
Being an engineer first and a physician second, I much prefer to avoid reinventing the wheel (life is already too short anyway) and I believe there is much to learn from species that already escaped or never encountered senescence (since aging is more frequent in complex species, you could also say aging is a new phenomenon on the evolutionary scale). Besides, simple organisms can produce cures for complex humans like penicillin did which was first produced in a simple fungus to defend itself of bacteria.
As a practical example, studying aging in several different species allowed me to not fall prey to the hype of telomerase as a cure for aging since many closely-related species maintain the length of their telomeres throughout lifespan and yet, they still age (e.g. some species of sea urchins). Telomerase could be useful as a specific cure for lack of regeneration in old age, but I don’t see it as a cure for aging itself.