Why do we age and eventually die? For most us, ageing is simply accepted as a part of life: biological systems, over time, deteriorate and eventually become non-functional. Intuitively, we likely tie this process in with the second law of thermodynamics: that the entropy (degree of disorder) of any isolated or closed system will increase over time.
But we are not closed systems – as biological beings, we metabolize substances taken in from beyond our bodies to rebuild and replace our cells. So is there any reason that we could not modify our cells to not age?
That is the question raised by biologist Michael Levin in an interview last year with podcaster Lex Fridman (embedded below for your convenience), in which he provided the example of the humble planarian – a type of flatworm that grows to about a little less than an inch in length – as a biological system that is, in fact, eternal.
The first thing is planaria are immortal – so they do not age. There’s no such thing as an old planarian, so that right there tells you that these theories of thermodynamic limitations of on lifespan are wrong. It’s not that ‘well over time everything degrades’ – no, planaria can keep it going for…how long have they been around, 400 million years?
In fact, Levin thinks planaria “hold the answer to pretty much every deep question of life”. Because it isn’t just that they do not age: they also can, quite amazingly, regenerate a full body from any piece of themselves.
So, you can cut them into pieces – the record is I think 276 or something like that – and each piece regrows a perfect little worm. Every piece knows exactly what’s missing, what needs to happen – in fact, if you chop it in half, as it grows the original tissue shrinks so that when the new tiny head shows up they’re proportional. So it keeps perfect proportion…their anatomical control is just insane.
This obviously has important lessons for regenerative medicine of the future, suggesting the possibility that we might one day be able to regrow amputated limbs. Levin elaborates further on this topic later in the interview, noting that he and co-researchers are – amazingly – already regrowing amputated limbs in frogs!
(Summary continues underneath the video. We have also written about Michael Levin’s revolutionary research here on the Grail previously.)
Furthermore, Levin notes the bizarre fact that regenerated planaria appear to remember things learned before they were separated from their head. “[Planaria are] smart, you can train them, and it turns out that if you train a planarian and then cut their heads off, the tail will regenerate a brand new brain that still remembers the original information,” Levin reveals.
Levin’s research has uncovered that regeneration of the bodily form of the planarian (and other creatures) is guided by electrical networks in the cells, and that the signals in those networks can be manipulated to make the body grow different organs. By doing so, he has been able to make two-headed planaria, and additionally found that this change is then inherited by future ‘generations’ (or more properly perhaps, regenerations), despite there being no change to the underlying DNA. This discovery changes our conception of DNA being the sole provider of our body’s ‘blueprint’.
So if you ask the question ‘where do body plans come from’ – how does the planarian know how many heads it’s supposed to have now? It turns out the DNA produces a piece of hardware that by default says one head, the way that when you turn on a calculator by default it’s a zero…every single time right when you turn it on, just a zero.
But it’s a programmable calculator as it turns out – so once you’ve changed that, next time it won’t say zero, it’ll say something else. The hardware-software distinction is really important: the hardware is essential, because without proper hardware you’re never going to get to the right physiology of having that memory. But once you have it, it doesn’t fully determine what the information is going to be – you can have other information in there, and it’s reprogrammable by us (and by bacteria, by various parasites and things like that, probably).
And perhaps the most puzzling thing overall about planaria is that they have all these ‘super-abilities’ despite their genome being an absolute mess. “Most animals when we get a mutation in our bodies, our children don’t inherit it”, Levin explains. “You could run around for 50-60 years getting mutations, but your children don’t have those mutations because we go through the egg stage.”
However, “planaria tear themselves in half and that’s how they reproduce, so for 400 million years they keep every mutation that they’ve had that doesn’t kill the cell that it’s in – so when you look at these planaria their bodies are what’s called mixoploid, meaning that every cell might have a different number of chromosomes…they look like a tumor, the genome is an incredible mess because they accumulate all this stuff.”
“This is kind of a scandal,” Levin admits. “Why does the animal with the worst genome have the best anatomical control, the most cancer resistance, is the most regenerative? It’s really a major puzzle.”
Learn more about Michael Levin’s groundbreaking research in this previous Daily Grail story.
