The Human Quest to Understand Immortality

Factorialist: Quest for immortality and the cryogenics

As humans, we occasionally have a stressful week or two, and many of us tend to drone on about it to whoever will listen, but for a tiny drone ant two weeks is literally a lifetime. From mere hours to hundreds of years, life expectancy is dramatically variable among the different species. The oldest living human, Jeanne Calment from France, lived to the impressive age of 122, while a Galápagos giant tortoise named Harriet, who was about the size of a dinner table, clocked in at an extraordinary 175 years old.

Even more surprisingly, a 507-year-old ocean clam (Arctica islandica) has been found off the coast of Iceland, a discovery so special that the clam was given a nickname: Ming the clam. Luckily for Ming, clams don’t have brains; after all, just sitting in the ocean for 507 years would be painfully boring if cursed with the capacity to realize it. For all the fuss, though, even incredibly old creatures still eventually die, because death is a natural part of life. At least, that’s what we’re taught. But if death is so natural, why does nature allow animals to have such vastly different lifespans, and why are there animals that can avoid aging altogether?

Factorialist: Quest for immortality and  the longest living organisms, like Ming the clam
 

When “Age doesn’t Matter” is actually true…

Those lucky organisms that don’t appear to age are said to be biologically immortal. While they can still die from disease, predation, or poor environmental conditions, they don’t show signs of functional decline and aren’t any more likely to die with increasing age. This obviously isn’t the case for humans. As the years fly by our eyesight, hearing, and other functions begin to fail, and the probability of death increases. Your grandparents are, unfortunately, more likely to pass away than you are.

The lobster, on the other hand, doesn’t weaken with age, and is thus not only delicious but also biologically immortal. The catch is that this doesn’t necessarily mean they will have a long lifespan. Lobsters still die from exhaustion while molting, an incredibly energy intensive process, or through finding themselves on the shiny silver platters of the wealthy. So if death is a reality even for animals hyped up as biologically immortal, is death simply an inevitable and natural consequence of life? A good place to begin our search for answers is with the process that shaped nature itself: evolution.

Evolution: Have babies and then die

Factorialist: Quest for immortality and spreading genes
 

“The earlier an organism has offspring, the shorter that organism’s life will be.”tweet

There’s a pattern in nature: the earlier an organism has offspring, the shorter that organism’s life will be. Evolution’s main aim is for an organism to survive until it breeds, or for animals like humans, long enough to change smelly diapers, teach life skills (like not to eat mud pie), and then kick the children out of the home. Nature’s equivalent of the financial burden of children is that once an animal has successfully raised its offspring, it competes with it for important resources, like food.

The danger of population overcrowding makes the death of one generation of a species beneficial for the survival of the next. In evolution, the early bird gets the worm, until it has chicks – then it has to fight them for the worm. On top of this, genetic mutations that cause disabilities or diseases that are expressed with old age, or after the organisms have had offspring, will accumulate in a species and naturally shorten its lifespan. In this way death is not only natural; it’s also necessary for the survival of a species.

Factorialist: Quest for immortality and the longest living organisms, like biologically immortal LobstersAnother interesting theory is that the lifespan of a species is influenced by the number of predators with which it has evolved. Take the humble house mouse, for example. Mice have many mighty predators – something we can all appreciate after watching the family cat deposit its trophy mouse guts on the carpet – and they only live for around one to three years. To understand why, let’s imagine two mice with slightly different evolutionary adaptations.

The first mouse reaches sexual maturity quickly, has pups, and then, sadly, gets gobbled up by a cat. In this scenario, the genetic code that causes early maturation is passed on to offspring. The second mouse reaches sexual maturity at a later age, and therefore doesn’t get the opportunity to have pups before also being eaten by a cat. Bummer. She’s lost the lottery of life, and her genetics that favor later sexual maturity aren’t passed on. By this mechanism, a species with many predators evolves to reproduce quickly and in large numbers.

The wild rabbit, which lives for an average of five years, is the perfect example. There’s a reason we coined the phrase breeding like rabbits. They can have up to 12 kits in just one litter. Similarly, the housefly generally lives for less than a month, but it lays a ridiculous number of eggs – 500 or more. Conversely, species with fewer predators evolve to have longer lives, because they have the opportunity to select against genetic traits that cause an early death.

This complex interplay of different evolutionary pressures has shaped what we call natural today, but it’s only one part of the story. The length of a natural lifespan is determined by biological processes that occur at a cellular level.

Telomeres: Nature’s ticking time bomb?

Factorialist: Quest for immortality and telomeres
 
Recently, scientific advances have begun to unravel basic cell division’s hidden role in determining lifespan. During cell division, accurate duplication of chromosomes (tightly compacted packages of DNA) is crucial, in order to avoid genetic defects or damage to DNA. Lucky for us we have telomeres, repeated sequences of DNA at the end of each leg of our chromosomes that lack important genetic information. Telomeres act as disposable buffer zones that protect the important DNA within our chromosomes and stop adjacent chromosomes from fusing together. Think of them as the DNA version of that handy little bit of plastic at the end of your shoelaces (they’re called aglets, by the way) that protects them and prevents fraying. Where would we be without them?

TelomeresAs they prepare to divide, cells make genetically identical copies of chromosomes, but the enzymes responsible for duplicating the DNA can’t carry out the duplication to the very end of a chromosome. A useful analogy is that of a bricklayer standing atop a wall. His task is to copy the layer of wall he’s standing on, and he does this successfully until he finds himself standing atop the last brick. Uh-oh. This last brick is analogous to the tiny bit of DNA that can’t be copied. Fortunately for us, with every cell division, instead of losing a fraction of our precious genetic instructions, we lose a little bit of the telomere at the end of the chromosome. Phew, our genetic hard drive is safe.

But, unfortunately for us, telomeres don’t last forever. Newborn babies are born with white blood cells that contain telomeres with 8000 base pairs (the bits of chemical code that make up DNA), while the same cells in the elderly are much shorter, with only 1500 base pairs. With each cell division, and with increasing age, telomeres get shorter. Eventually, they get so short that the cell can’t divide without corrupting genetic information. For the average human cell, this limit is 50 to 70 divisions, after which the cell is said to have become senescent and dies. This biological limit, known as the Hayflick limit, is one of the reasons that we don’t naturally live forever. Telomeres are nature’s built-in aging clock.

Do longer telomeres mean a longer life?

“Nature has equipped us with telomeres, and they’re both a blessing and a ticking time bomb.”tweet

Nature has equipped us with telomeres, and they’re both a blessing and a ticking time bomb. The length of telomeres varies for different animals, and, theoretically, the more telomeres an organism has, the longer its cells can safely divide. Our telomeres provide us with a tantalizing biological clue as to why natural lifespans are so variable.

A number of animal studies have shown a correlation between the length of telomeres and lifespan. A 2012 study by the University of Calgary in Canada concentrated on telomere variation in different domestic dog breeds with average lifespans ranging from six years for a bulldog to fourteen years for a miniature poodle. The study concluded that telomere length positively correlates with canine lifespan, consistent with the theory that telomere length plays a vital role in determining lifespan. It also found that canines lose telomeric DNA approximately 10 times faster than humans do, a figure strikingly similar to the ratio of average lifespans between humans and our furry friends. How many parents have explained the passing of the old family dog by claiming that a dog year is equal to ten human years? Yet these links haven’t only been observed in dogs. Evidence is emerging that suggests telomere length plays a role in determining human lifespans too. Yes, that means you.

A 2015 Danish study found a correlation between telomere length and mortality in humans. The study, involving over 64,000 individuals recruited from 1991 onwards, concluded that the shorter your telomeres, the larger your chance of dying. This was true even after factoring in lifestyle factors such as smoking, lack of exercise, BMI, and alcohol consumption, all of which have also been shown to shorten telomeres. While other studies have failed to demonstrate any correlation between telomeres and lifespan, and we can be sure that it’s a complex process with lots left to discover, the link between lifespan and telomeres is convincing enough that plenty of research now focuses on how to increase telomere length, and as a result, extend our lifespans.

Telomerase: Unlocking the power of telomeres

Telomeres
 
In a feat that is nothing short of amazing, telomere length can be extended through the action of an enzyme called telomerase. However, in most animals – including humans – telomerase is active only in germ cells and some stem cells, and this contributes to aging and, eventually, death. Our friend the lobster is a rare example of an animal that expresses this enzyme in most of their bodily tissue throughout their adult lives. It is their constant replenishment of telomeres that allows for essentially unlimited cell division, and theoretical – but, as we know, not practical – immortality. This is an extraordinary feat of nature that actively challenges the concept that age related death is “natural”. And the lobster is not alone.

The Planarian: Immortality and celibacy

Factorialist: Quest for immortality and asexual reproduction
 
Unlike the helpless earthworms that the curious among us experimented on as children, the planarian flatworm can fully regenerate into two separate worms when split in half. A piece as tiny as 1/279 of the animal can regenerate into a complete worm within weeks. This is a bit like a whole human regenerating from one of our stubby toes! But don’t try this at home! The regeneration doesn’t even have to be of a complete body; if you cut the head of a planarian flatworm in half it will simply spawn two heads and keep on living its life. They can grow new muscles, guts, and even brains. And they’re not just tiny insignificant worms. Some species measure less than a millimeter, but others (like Bipalium kewense, a predatory flatworm found in Southeast Asia) can reach a length of 60 centimeters. Magic tricks aside, most of us wouldn’t consider the ability to survive being cut in half as natural, yet for some remarkable creatures it is.

factorialist_planarian_2The planarian flatworm’s nightmarish ability to regenerate lies with self-renewing stem cells called neoblasts that replace aging cells and regenerate tissue. In most organisms, as stem cells divide (for example, to heal wounds), over time they become less capable of division and tissue replacement. This is evident in the aging of human skin. However, stem cells in asexual planarian flatworms bypass this aging process and can continue cell division indefinitely.

And researchers believe they’ve found the equivalent of the telomerase enzyme that’s responsible. Experimentally blocking the enzyme’s function resulted in shortening of the flatworm’s telomeres during regeneration, while enabling the enzyme restored telomere lengths. But this link wasn’t established for sexually reproducing flatworms. Perhaps nature chose living forever at the expense of giving up sex. Which would you choose? Regardless, it’s an exciting area of research and further studies into creatures like this could eventually reveal nature’s allusive secrets of immortality.

The more we discover about nature, the more we’re tempted to highjack nature’s processes to increase our own lifespans. Is telomere shortening a disease that we can cure, or is it a fundamental natural limit that shouldn’t be messed with? Aging and death is programmed into us by millions of years of evolution, and what we call nature is a complex mess of evolutionary traits and biological functions that vary from one species to another. While natural may not be an easy word to define, death remains an integral part of nature, at least for now. Of course, it’s not unreasonable to wonder if one day this might change, because while death may be natural, hoping for immortality is part of human nature.