I’m preparing for graduate school in tissue engineering via bioprinting. I was motivated by these considerations.
My sense is that ageing is both an evolutionary response to cancer and an entropic inevitability. No matter how much you supplement the body, eventually deleterious mutations will accumulate. The complexity of cellular systems makes them very difficult to improve on.
The strategy I envision is that we’ll learn how to manufacture healthy, fresh tissues and organs from the recipient’s own cells. While it’s very hard to improve on the cell’s natural mechanisms, we can harness it in this way to rejuvenate at the level of tissues and organs. People will receive periodic transplants of fresh organs built from their own cells.
(1) Aging is not entropy (second law of thermodynamics). In fact, both young and old individuals are in very high entropic states, and it is not entropy that kills people when they die of aging. Instead, it is the accumulation of biological ‘damage’ (i.e. hallmarks of aging) described in the original post. If aging was inevitable due to entropy it would be impossible according to the laws of physics for biological organisms such as the hydra and tortoise to display negligible senescence, and for sharks to achieve the 400+ lifespans that they do without any increase in mortality risk.
Thanks for writing the OP and for your response, I now see you mentioned this in the original. I’m excited to check your links out.
Other commenters mentioned that an issue to anti-aging research in humans is the regulatory barriers.
Part of the reason I’m interested in tissue engineering is that it may circumvent that issue to some extent. You can do your research relatively freely on tissue until you’re able to replicate a certain organ, test it on people who need a transplant, and “patch together” an approach to life extension in this way.
I wasn’t precisely sure about the anti-aging applications of tissue engineering, so I asked a colleague and this is what he said:
The first application of tissue engineering is preclinical drug testing. Drug development starts with preclinical animal testing, but the vast majority of drugs that work in animals do not work in people. Estimates vary, but about 97% of preclinical leads that enter clinical trials do not exit them. Human organoids are a potential alternative that could allow at least some of this preclinical data to be obtained from humans, not animals, and hopefully be more accurate.
The second application of tissue engineering is testing cell therapies. Many future rejuvenative aging therapies will probably involve permanently engrafting engineered cells into people. If you can, say, engineer dermis in the lab, you can assess whether therapeutic fibroblasts can engraft in that dermis and whether they evenutally become cancerous.
The third application of tissue engineering is clinically putting engineered tissue into people. For example, some aging researchers are interested in thymic regeneration, but a potentially easier alternative would be adding engineered thymus-like tissues to a person instead of regenerating the involuted thymus.
I think the direction you’ve chosen, tissue engineering, will be very useful. One important organ for aging to be rejuvenated/replaced is thymus, whose degeneration is a major cause of declining immunity with aging.
“No matter how much you supplement the body, eventually deleterious mutations will accumulate.” yes, however, in nature, deleterious mutations don’t accumulate in all species. Hydra is an example/exception. It replaces its cells at such a fast rate, that this is an important reason why it doesn’t accumulate mutations (and other damage) and manages to be biologically immortal. In fact, the direction you’ve chosen for research would do the same but at the level of tissues/organs, not cells.
I’m preparing for graduate school in tissue engineering via bioprinting. I was motivated by these considerations.
My sense is that ageing is both an evolutionary response to cancer and an entropic inevitability. No matter how much you supplement the body, eventually deleterious mutations will accumulate. The complexity of cellular systems makes them very difficult to improve on.
The strategy I envision is that we’ll learn how to manufacture healthy, fresh tissues and organs from the recipient’s own cells. While it’s very hard to improve on the cell’s natural mechanisms, we can harness it in this way to rejuvenate at the level of tissues and organs. People will receive periodic transplants of fresh organs built from their own cells.
(1) Aging is not entropy (second law of thermodynamics). In fact, both young and old individuals are in very high entropic states, and it is not entropy that kills people when they die of aging. Instead, it is the accumulation of biological ‘damage’ (i.e. hallmarks of aging) described in the original post. If aging was inevitable due to entropy it would be impossible according to the laws of physics for biological organisms such as the hydra and tortoise to display negligible senescence, and for sharks to achieve the 400+ lifespans that they do without any increase in mortality risk.
(2) Your description of ‘deleterious mutations’ is accurate—genomic instability which includes DNA damage (as well as chromosomal rearrangement) is one of the 9 hallmarks of aging. But like all of the hallmarks, it is something we can attenuate. There are currently clinical trials for several DNA repair therapies such as nicotinimide mononucleotide (NMN), an NAD+-precursor molecule in Sinclair’s lab at Harvard, and nicotinomide riboside (NR) which is being developed by the biotech company Chromadex.
For a good primer on genomic instability, I encourage you to read this article from Lifespan.io.
Thanks for writing the OP and for your response, I now see you mentioned this in the original. I’m excited to check your links out.
Other commenters mentioned that an issue to anti-aging research in humans is the regulatory barriers.
Part of the reason I’m interested in tissue engineering is that it may circumvent that issue to some extent. You can do your research relatively freely on tissue until you’re able to replicate a certain organ, test it on people who need a transplant, and “patch together” an approach to life extension in this way.
Great to hear you are interested in contributing!
I wasn’t precisely sure about the anti-aging applications of tissue engineering, so I asked a colleague and this is what he said:
So, it definitely seems important!
I think the direction you’ve chosen, tissue engineering, will be very useful. One important organ for aging to be rejuvenated/replaced is thymus, whose degeneration is a major cause of declining immunity with aging.
“No matter how much you supplement the body, eventually deleterious mutations will accumulate.” yes, however, in nature, deleterious mutations don’t accumulate in all species. Hydra is an example/exception. It replaces its cells at such a fast rate, that this is an important reason why it doesn’t accumulate mutations (and other damage) and manages to be biologically immortal.
In fact, the direction you’ve chosen for research would do the same but at the level of tissues/organs, not cells.