Lifespan: what can we learn from these animal-champions?

There’s a type of may­fly whose females emerge, mate, lay their eggs and die in under five minutes. At the oth­er end of the longev­ity spec­trum, sharks swim­ming in the fri­gid waters around Green­land have been estim­ated to live 400 years. The diversity of lifespans in the nat­ur­al world is as incred­ible as the range of sizes, shapes, diets and life­styles found in liv­ing creatures. So, what can we learn from anim­als about how to age well ourselves?

At around a mil­li­metre long and almost trans­par­ent, you’re prob­ably going to need a micro­scope and some help to spot C. eleg­ans, the sci­entif­ic name for an unas­sum­ing nem­at­ode worm that has become one of the stal­warts of age­ing research. These nem­at­odes were ori­gin­ally found by sci­ent­ist Sydney Bren­ner in his com­post heap¹, because he was look­ing for a new ‘mod­el organism’—a creature which shares enough bio­logy with more com­plex anim­als, includ­ing humans, to learn what makes us tick, but is easi­er to work with in the lab.

Worms have lots of advant­ages when it comes to longev­ity research: being so tiny, you can grow hun­dreds of them on a tiny plate in the lab, and their nat­ur­al lifespan is just two weeks, mean­ing detailed exper­i­ments which would take years or dec­ades in longer-lived anim­als can be con­cluded in just a few months.

Of their many con­tri­bu­tions to bio­logy research, the most remark­able thing that these worms have taught us is that even chan­ging a single gene can be enough to dra­mat­ic­ally extend lifespan. The first worm ‘longev­ity gene’ was dis­covered in the late 1980s, and added about 50% to worm lifespan²—but the idea that a single genet­ic change in a creature with 20,000 genes could extend lifespan was so out­land­ish that the res­ults didn’t gain much trac­tion. A few years later, anoth­er gene was found that doubled worm life expect­ancy, from two weeks to four³—and this even more strik­ing res­ult, in a totally unre­lated gene, caused sci­ent­ists to sit up and take notice.

There’s now a huge back-cata­logue of genes that can increase lifespan: over 600 in C. eleg­ans, and hun­dreds more in oth­er organ­isms⁴. For example, the world’s longest-lived mouse didn’t have the per­fect diet and exer­cise regime, or some mir­acle drug—the ‘Laron mouse’ has a single muta­tion in a gene related to growth hor­mone, and the reign­ing longev­ity cham­pi­on died just a week short of its fifth birth­day, where nor­mal mice rarely live more than three years⁵.

Why do worms only live for 14 days and mice a few years, while Green­land sharks can live to 400? Indeed, why do creatures grow frail and die at all? Evol­u­tion is often sum­mar­ised as ‘sur­viv­al of the fittest’—so why does it per­mit us to grow old and die? Enter the opos­sum, an Amer­ic­an mar­supi­al that looks like a mouse the size of a cat, that provided a serendip­it­ous con­firm­a­tion of how this can hap­pen in the wild.

Eco­lo­gist Steve Aus­tad star­ted study­ing these crit­ters when they kept wan­der­ing into a colleague’s traps inten­ded for trop­ic­al foxes. He decided not to let the unin­ten­ded cap­tives go to waste, and tagged them with radio col­lars. But, as he con­tin­ued to study them, noticed some­thing remark­able: the incred­ible speed at which they aged. Anim­als would turn from fully-func­tion­al adults to decrep­it or deceased over a mat­ter of months.

Why do opos­sums suf­fer such a rap­id fall from fit­ness? The answer, unfor­tu­nately for them, is that they’re deli­cious. Ima­gine life from the per­spect­ive of one of those fast-age­ing opos­sums: as a docile, cat-sized mouse, you’d make a great snack for a pred­at­or (like those trop­ic­al foxes Austad’s col­league was try­ing to catch). As a res­ult, more than half of wild opos­sums meet their end in the claws or talons of anoth­er creature. Opos­sums, then, age so rap­idly because of an evol­u­tion­ary trade-off⁶: there’s no point stay­ing fit and healthy until the age of 10 if you’re almost cer­tain to be eaten in your first three or four years. Instead, evol­u­tion con­cen­trates an opossum’s ener­gies on hav­ing lots of babies before pred­at­ors devour it, not wor­ry­ing about wheth­er its body will fall apart should it some­how dodge becom­ing someone’s dinner.

Thus, Aus­tad the­or­ised, if he could find a pop­u­la­tion of opos­sums some­where without pred­at­ors, evol­u­tion might take a dif­fer­ent tack: grow up and grow old at a more leis­urely pace, not rush­ing to lit­er­ally and meta­phor­ic­ally out­run pred­at­ors by hav­ing kids as fast as pos­sible. He did indeed find such a place: Sapelo Island, just north of Flor­ida, which, after sep­ar­at­ing from US main­land 4,000 years ago, lost its big car­ni­vores. And 4,000 years may be a long time by human stand­ards, but it’s brief enough evol­u­tion­ar­ily that this provides an oppor­tun­ity to watch nat­ur­al selec­tion in action.

What he dis­covered on Sapelo was a pop­u­la­tion of fear­less opossums—unlike their main­land coun­ter­parts who were nervous and noc­turn­al, they’d walk around in plain sight dur­ing the day. And, where main­land opos­sums had a max­im­um lifespan of 2.5 years, Sapelo’s fear­less ver­sions could live for nearly four⁷. Over per­haps a couple of thou­sand opos­sum gen­er­a­tions, an eleg­ant nat­ur­al exper­i­ment had shown us why we age: because thrifty evol­u­tion won’t invest the resources to keep you alive if you’re likely to be dead from anoth­er cause anyway.

While mov­ing to a pred­at­or-free island and gradu­ally breed­ing longer lived humans over thou­sands of years might sound like some­thing from a dysto­pi­an sci-fi nov­el, the les­son from opos­sums can lead us to some­thing more action­able. If you want to find really long-lived anim­als, find those at low risk from predators—and per­haps we can learn some­thing about longev­ity from their biology.

A great example is the bowhead whale. At 100 tonnes, these are some of the largest anim­als ever to have lived and, cor­res­pond­ingly, very rarely eaten—a hand­ful of reports doc­u­ment pods of orcas attack­ing bowheads, but their main threat was the bar­bar­ic whal­ing industry, which is thank­fully now largely a thing of the past. As a res­ult, these ocean giants evolved one of the longest lifespans in nature—the old­est whale ever recor­ded was estim­ated to be 211 years old⁸.

Anim­als so huge as to be effect­ively ined­ible also hav­ing incred­ible lifespans accords pre­cisely with evol­u­tion­ary expectations—but presents some­thing of a para­dox when con­sidered on a cel­lu­lar scale. The size of a cell is more or less con­stant wheth­er you’re a human, a mouse, or a 100-tonne whale, which means a bowhead has approx­im­ately 1000 times as many cells as a per­son does, and they also live at least twice as long. The conun­drum this leads to is simple: why aren’t all bowhead whales abso­lutely riddled with cancer?

Can­cer is caused by ran­dom mis­takes appear­ing in a cell’s genet­ic code. That’s one reas­on that can­cer is a dis­ease of age­ing: the longer you’ve been alive, the more time these genet­ic typos have to accrue. It also means that every cell is a risk, so hav­ing 1000 times as many cells should sub­stan­tially increase your chances. And yet, whales don’t seem to be giant, swim­ming tumours. What’s their secret? One sug­ges­tion has come from rum­ma­ging around in the bowhead whale’s genet­ic code: they have addi­tion­al cop­ies and subtle vari­ations on genes respons­ible for DNA repair⁹, per­haps mean­ing that their cells are more vigil­ant to muta­tions that could give rise to can­cer. As well as being can­cer-res­ist­ant, bowheads also don’t seem to get catar­acts, the cloud­ing of the lens of the eye that affects many anim­als (includ­ing humans) as we age, per­haps due to anti­ox­id­ant chem­ic­als in their lenses¹⁰. And mak­ing it to such incred­ible ages requires that whales dodge or post­pone all the major ail­ments that make our lives miser­able long before we reach 200 years old. Whales are a tough anim­al to study in the lab, but their bio­logy almost cer­tainly har­bours a few longev­ity tips and tricks that we’d do well to go fish­ing for.