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.