Highlights of Comparative and Evolutionary Aging

Author’s Note: the pur­pose of this se­quence is gears, i.e. phys­iol­ogy and molec­u­lar/​cel­lu­lar-level mechanisms, not evolu­tion. This post con­tains only some bare-min­i­mum back­ground in­for­ma­tion as con­text for the rest; check out Will Brad­shaw’s se­ries for a short in­tro which does bet­ter jus­tice to evolu­tion­ary the­o­ries of ag­ing in their own right.

Many species do not age: hy­dra, some tur­tles, rough­eye rock­fish, naked mole rats, and prob­a­bly many oth­ers which we just haven’t sat around and watched long enough yet. This does not mean these or­ganisms are im­mor­tal—in the wild, they get eaten or in­fected sooner or later. But their phys­iol­ogy does not change with age; post-de­vel­op­ment, older or­ganisms look phys­iolog­i­cally iden­ti­cal to younger or­ganisms. They don’t get more wrin­kles, or weaker mus­cles, or in­flamed joints. In par­tic­u­lar, non-ag­ing species are not more likely to die soon as they get older. We call it “neg­ligible senes­cence”.

Con­trast to hu­mans:

This is the Gom­pertz-Make­ham Law of mor­tal­ity: af­ter de­vel­op­ment, hu­mans’ an­nual death rate in­creases ex­po­nen­tially with age (dou­bling time ~8 years). For naked mole rats and other non-ag­ing species, this curve would be com­pletely flat af­ter child­hood. (Side note: that bump around age 20 is the car-ac­ci­dent bump).

This raises an evolu­tion­ary puz­zle: ag­ing ob­vi­ously en­tails loss of func­tion­al­ity and in­creased death rate. Surely those things can’t be benefi­cial to or­ganism fit­ness. But we know it’s phys­iolog­i­cally pos­si­ble for or­ganisms to not age, so if ag­ing isn’t evolu­tion­ar­ily benefi­cial, why do or­ganisms ever age? Why haven’t all or­ganisms evolved neg­ligible senes­cence?

Well, once an or­ganism has re­pro­duced, evolu­tion doesn’t re­ally care what hap­pens any more. Sure, slowly break­ing down over time won’t be benefi­cial, but it’s not a sig­nifi­cant dis­ad­van­tage ei­ther, as long as the kids are grown. And in na­ture, the vast ma­jor­ity of or­ganisms will die to pre­da­tion or dis­ease or star­va­tion pretty quickly any­way. So, when­ever there’s an op­por­tu­nity to gain some early-life ad­van­tage in ex­change for ag­ing later in life, that’s go­ing to be an evolu­tion­ar­ily ad­van­ta­geous trade-off. This is the “an­tag­o­nis­tic pleiotropy” evolu­tion­ary the­ory of ag­ing: most or­ganisms age be­cause there’s lit­tle se­lec­tive pres­sure not to, and there are ad­van­tages to be had from trade-offs in fa­vor of early life.

This ties in to the gen­eral the­ory of “life his­tory strate­gies”: some crea­tures pro­duce large num­bers of offspring but don’t in­vest much in rais­ing the chil­dren, while oth­ers pro­duce just a few offspring and in­vest heav­ily in them. Crea­tures which in­vest heav­ily in their chil­dren will be more evolu­tion­ar­ily use­ful post-re­pro­duc­tion, so we should ex­pect them to have longer lives; crea­tures which don’t in­vest much won’t gain as much fit­ness by liv­ing longer. At the ex­treme, we see or­ganisms which spend their en­tire metabolic re­sources on re­pro­duc­tion, max­i­miz­ing the num­ber of young pro­duced, and die shortly af­ter.

There is some im­pres­sive ev­i­dence in fa­vor of an­tag­o­nis­tic pleiotropy in com­par­a­tive (i.e. cross-species) ag­ing—life his­tory strate­gies do turn out to cor­re­late quite heav­ily with lifes­pan, by mul­ti­ple mea­sures, and the mea­sures which we’d ex­pect to bet­ter re­flect life his­tory tend to screen off those which re­flect it less well. I’m not go­ing to go into the de­tails here, but Robert Ark­ing’s “The Biol­ogy of Aging” has a de­cent chap­ter on it (chap­ter 4).

For hu­mans speci­fi­cally, there’s some ev­i­dence that we have higher-than-usual evolu­tion­ary pres­sure against ag­ing. In par­tic­u­lar, hu­mans are quite long-lived for an­i­mals our size. In gen­eral, larger an­i­mals have longer lifes­pans—mice live ~3 years, li­ons and gazel­les live 10-15 years, elephants live 50-70… yet hu­mans out­live elephants. Our long life span is typ­i­cally at­tributed to very long ges­ta­tional pe­ri­ods com­bined with a very high de­gree of parental in­vest­ment in chil­dren. In the an­tag­o­nis­tic pleiotropy <-> life his­tory pic­ture, high-parental-in­vest­ment strate­gies are gen­er­ally as­so­ci­ated with long species life-spans, and vice-versa: when or­ganisms don’t in­vest in their progeny, they are less evolu­tion­ar­ily use­ful in old age. Since we hu­mans in­vest ex­tremely heav­ily in our offspring, we are un­usu­ally use­ful in old age, and thus have un­usu­ally long lifes­pans.