Study of aging, human longevity and anti-aging therapeutics is a young field. So far most of the research has concentrated on non-human life forms such as yeast cells, worms and mice. There’s been quite a few discoveries and progress made in understanding what it means, for example, for a mouse to age.
Perhaps the biggest revelation coming out of those studies in the last decade has been that aging is a process that is not necessarily written into the genes, not a natural one so to speak, not one driven by underlying laws of physics. It is a process of decay, but there's nothing (that has yet been discovered at least) that would stop us from theoretically reversing it. For one, aging process in mice has been stopped in lab environment and even reversed [source].
However, the road from those studies to future wide application of anti-aging treatments for humans is long and unclear at this point. Part of the issue is that the FDA does not consider aging as an ailment today, so essentially no drug can be developed to treat it. There is an increasing number of academics calling for officially recognizing it as a disease and going even further stipulating that it is the underlying root cause to all other diseases generally considered age-related, such as cancer, heart disease, etc. Tackling the underlying root cause would potentially address and solve many ailments.
A recent Telegraph article quotes Dr. Calimport of Liverpool University [source]
‘When senescent cells build up in the skin causing wrinkles it is considered a ‘natural change.’ Yet when senescent cells build up in the heart and blood vessels, causing blood vessels to calcify, we call it ‘cardiovascular disease.’ This is an error of logic and categorization and not due to the intrinsic nature or complexity of pathology or disease.’
Part of the issue is that the FDA does not consider aging as a disease today, so essentially no drug can be developed to treat it.
How is then aging defined by those medical and academic professionals that are forging ahead? Longevity expert Aubrey de Grey has spoken widely about seven types of aging damage in human bodies:
- Mutations in Chromosomes causing cancer due to nuclear mutations/epimutations. These are changes to the nuclear DNA (nDNA), the molecule that contains our genetic information, or to proteins which bind to the nDNA.
- Mutations in Mitochondria. Mitochondria are components in our cells that are important for energy production. They contain their own genetic material, and mutations to their DNA can affect a cell’s ability to function properly.
- Junk inside of cells. Our cells are constantly breaking down proteins and other molecules that are no longer useful or which can be harmful. Those molecules which can’t be digested simply accumulate as junk inside our cells.
- Junk outside of cells. Harmful junk protein can also accumulate outside of our cells.
- Cellular loss. Some of the cells in our bodies cannot be replaced, or can only be replaced very slowly, more slowly than they die. This decrease in cell number causes the heart to become weaker with age.
- Cell senescence. This is a phenomenon where the cells are no longer able to divide, but also do not die and let others divide. They may also do other things that they’re not supposed to, like secreting proteins that could be harmful.
- Extracellular protein crosslinks. Cells are held together by special linking proteins. When too many cross-links form between cells in a tissue, the tissue can lose its elasticity and cause problems.
Let's zoom in on the first one, mutations in chromosomes, specifically mutations to structures called telomeres. Telomeres are the caps at the end of the chromosomes that package the DNA and protect it from damage, much like plastic caps on the end of a shoelace.
Every time a cell divides and it happens all the time (our cells divide continuously) our DNA is replicated and every time this happens, telomeres get a little bit shorter. When they get too short they send signals to our cells to stop dividing. Once that occurs there is less regenerations of cells which can lead to disease.
Good news is that the length of telomeres is malleable.
In 2009, Elizabeth Blackburn, Carol Greider, and Jack Szostak were awarded Nobel prize for discovering that chromosomes are protected by telomeres and associated enzyme telomerase that functions by lengthening telomeres. As we age we produce less and less of that enzyme. So as we get chronologically older the length of telomeres gets shorter. The length is also affected by lifestyle choices (diet, social life, neighborhood you live in, stress). Studies conducted on stress levels found direct link between perceived stress levels and shortening of telomeres. [source]
As noted earlier, we are just at the beginning stages of this journey, both from a regulatory perspective but also scientific one. This does not stop Aubrey de Grey from putting out rough estimates that in 17 years we will have 50% chance of achieving successful age reversal in humans, as expressed during his recent appearance on Joe Rogan podcast [source]. This is purely from scientific point of view as judged by current rate of progress.
Chemistry is a combinatorial system that is so big we don’t know most of what’s in it...
Human body is a complex machine. The search space for potential links between various mechanisms, their intricate interconnectedness, and the chemical processes occurring between and within them is mind bogglingly vast.
As one multi-disciplinary thinker Eric Smith expressed it on a Jim Rutt podcast recently:
“Chemistry is a combinatorial system that is so big that we don’t know most of what’s in it. We don’t know what will happen.. We don’t have a system for searching systematically and as a consequence, we don’t have the ability to reason about it the way we reason about in any mature science. In most mature sciences, we start with a hypothesis. When we get to a point where we get stuck we have the ability to backtrack to the last place where we knew something and take a different path. In spaces that are so big such as chemistry we don’t know how to search them. Instead we rely on the expertise that any given person or community has in ad-hoc fashion, and we explore a region that way. Then, if it doesn’t have what we want, we go back to exploring.”
Searching for new drugs is a lot like the process described above. However, machine learning is making great strides in this space. Quantum computing is opening up new avenues as well. Specifically, the ability to search vast combinatorial spaces looking for novel patterns that would take years if not more for humans to discover in an ad-hoc method.
Taking scientific developments aside, currently we've socially accepted death as natural part of what it means to be human, whether from religious point of view or more generic moral standpoint. What will it take for humans, society at large to move beyond that mindset, realizing death might not be as natural of a process as we've grown to accept it?
Let's end on a quote from David Gems, geneticist and biogerontologist:
“We must draw aside the rosy veil of tradition and face aging for what it is, and in all its horror: the greatest disease of them all”
