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

Andrew Steele
Andrew Steele
PhD in physics from the University of Oxford, Science Writer and Presenter

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?

1. Worms

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.

2. Opossums

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.

3. Whales

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.

1Mark G. Sterken et al., The lab­o­ra­to­ry domes­ti­ca­tion of Caenorhab­di­tis ele­gans, Trends Genet. 31, 224–31 (2015). DOI: 10.1016/j.tig.2015.02.009
2D. B. Fried­man andT. E. John­son, Three mutants that extend both mean and max­i­mum life span of the nema­tode, Caenorhab­di­tis ele­gans, define the age‑1 gene J. Geron­tol. 43, B102–9 (1988)
3C. Keny­on et al., A C. ele­gans mutant that lives twice as long as wild type, Nature 366, 461–4 (1993). DOI: 10,103 8/366 461 a 0
4GenAge data­base of age­ing-relat­ed genes
5Hol­ly M. Brown-Borg and Andrzej Bartke, GH and IGF1: Roles in ener­gy metab­o­lism of long-liv­ing GH mutant mice, J. Geron­tol. A Biol. Sci. Med. Sci. 67, 652–60 (2012). DOI: 10.1093/gerona/gls086
6Thomas Flatt and Lin­da Par­tridge, Hori­zons in the evo­lu­tion of aging, BMC Biol. 16, 93 (2018). DOI: 10.1186/s12915-018‑0562‑z
7Steven N. Aus­tad, Retard­ed senes­cence in an insu­lar pop­u­la­tion of Vir­ginia opos­sums (Didel­phis vir­gini­ana), J. Zool. 229, 695–708 (1993)
81. J. C. George et al., Age and growth esti­mates of bow­head whales (Bal­ae­na mys­tice­tus) via aspar­tic acid racem­iza­tion, Can. J. Zool. 77, 571–580 (1999)
9Insights into the evo­lu­tion of longevi­ty from the bow­head whale genome, Cell Rep. 10, 112–22 (2015). DOI: 10.1016/j.celrep.2014.12.008
101. D. Borch­man, R. Stim­mel­mayr and J. C. George, Whales, lifes­pan, phos­pho­lipids, and cataracts, J. Lipid Res. 58, 2289–2298 (2017)

Contributors

Andrew Steele

Andrew Steele

PhD in physics from the University of Oxford, Science Writer and Presenter

After a PhD in physics from the University of Oxford, Andrew Steele decided that ageing was the single most important scientific challenge of our time, and switched fields to computational biology. After five years using machine learning to investigate DNA and NHS medical records, he is now a full-time writer, author of Ageless: The new science of getting older without getting old, presenter and campaigner.