Three possible ways of turning back the clocks of ageing

Many of us think of the age­ing process as a fact of life. As humans, our risk of death ris­es by 10% each year thanks to the ever-tick­ing bio­log­i­cal clock of the age­ing process. Old­er peo­ple are more like­ly to suf­fer from dis­eases like can­cer and demen­tia, more like­ly to be frail, lose their sight, hear­ing or mem­o­ry, and much more besides.

How­ev­er, this process may not be so depress­ing­ly inevitable as we usu­al­ly imag­ine. Sci­en­tists now under­stand bet­ter than ever the fun­da­men­tal biol­o­gy of what caus­es us to grow old¹ and, most excit­ing­ly, how we can slow down or even reverse these bio­log­i­cal changes.

Here are three ideas to watch which could one day soon be turn­ing back your bio­log­i­cal clock.

One of the best known areas of age­ing research is study­ing ‘telom­eres’: pro­tec­tive caps which ensure the integri­ty of the ends of our DNA. How­ev­er, many cells in our bod­ies are con­stant­ly divid­ing: tis­sues like our skin, our blood and the lin­ing of our guts need to be con­stant­ly replaced due to wear and tear, and fresh­ly divid­ed new cells replace the old-timers. And unfor­tu­nate­ly, cel­lu­lar divi­sion comes at a cost to our telom­eres: they get short­er every time a cell divides.

The longer you live, the more times your cells will have divid­ed, and the short­er your telom­eres will be on aver­age. And mea­sur­ing telom­ere length isn’t just a round­about way of deter­min­ing how old you are—telomeres seem to have a causal role in age­ing too. Short­er telom­eres make age-relat­ed dis­eases more like­ly, and slight­ly mor­bid stud­ies of iden­ti­cal twins have found that the one with short­er telom­eres is like­ly to die soon­er.²

Sci­en­tists in the 1990s were thus very excit­ed by telom­erase: an enzyme which can extend telom­eres and, per­haps, make cells more youth­ful at the same time. Unfor­tu­nate­ly, its tenure as the immor­tal­i­ty enzyme didn’t last long: exper­i­ments in mice showed that telom­erase did indeed give their cells the poten­tial to divide far more times—at the cost of mas­sive­ly increas­ing the risk of the dead­ly dis­ease for whom exces­sive cell divi­sion is its modus operan­di: can­cer³.

Luck­i­ly, not all researchers aban­doned telom­erase as a poten­tial ther­a­py. In the last ten or fif­teen years, sci­en­tists have shown that it can extend the lives of mice if cou­pled with mea­sures to reduce the risk of can­cer, or if used inter­mit­tent­ly rather than acti­vat­ed con­tin­u­ous­ly as it was in ear­ly experiments.

The next step will be to try some of these ideas in humans⁴.

As we grow grey and wrin­kled on the out­side, so too the cells that make up our insides grow old. As we age, some of our cells become ‘senes­cent’ — the sci­en­tif­ic word for aged — and, in doing so, they can accel­er­ate the age­ing of the rest of our body too. We now under­stand that senes­cent cells aren’t just benign bystanders in the age­ing process, the cel­lu­lar equiv­a­lent of can­dles on a birth­day cake, but emit a tox­ic cock­tail of mol­e­cules which can increase the risk of heart dis­ease, can­cer, cog­ni­tive decline, and much more besides.

The good news is, it might not have to be this way. Sci­en­tists have come up with a num­ber of dif­fer­ent ways to kill these cells, while leav­ing the rest of the cells in the body intact. The idea fur­thest along in devel­op­ment is ‘senolyt­ic’ drugs, the first of which were dis­cov­ered in 2015⁵, and sev­er­al of which are already in human clin­i­cal trials.

A 2018 study⁶ showed the wide-rang­ing effects of giv­ing senolyt­ics to old mice: the ani­mals lived longer, which is a good start, but they also lived younger, with less chance of dis­ease, less frailty (mea­sured by per­for­mance on tiny mouse-sized gym equip­ment, from tread­mills, to tightropes, to wires to hang from), improved cog­ni­tion, and even bet­ter fur! This sug­gests that senes­cent cells aren’t just respon­si­ble for a sin­gle aspect of age­ing, but have effects on many or even all of its facets—meaning that remov­ing them could have wide­spread pre­ven­ta­tive med­i­cines for many dif­fer­ent diseases.

There are cur­rent­ly over two dozen com­pa­nies aim­ing to com­mer­cialise senolyt­ic treat­ments⁷, from drugs, to chem­i­cals called pep­tides, to encour­ag­ing our immune sys­tems to clear up these aber­rant cells. This diver­si­ty means we’ve got a lot of options in case some approach­es don’t work out—and means that senolyt­ics are a strong con­tender for our first true anti-age­ing treatment.

Its name makes it sound like sci­ence fic­tion — and, once you hear what it actu­al­ly entails, it only sounds more­so — but cel­lu­lar repro­gram­ming is prob­a­bly the hottest idea in age­ing biol­o­gy right now, with enor­mous poten­tial to improve our health. The ques­tion is, do we know enough to get it from sci­ence fact in the lab, to work­able med­ical tech­nol­o­gy in the real world?

The tech­nique was first dis­cov­ered in the mid-2000s⁸, when Japan­ese sci­en­tist Shinya Yamana­ka was try­ing to work out what enables cells in the embryo to grow up into any kind of cell in the body, from heart, to skin, to brain. He found that a com­bi­na­tion of just four genes, now known as the ‘Yamana­ka fac­tors’, was enough to revert any cell in the body to this ‘pluripo­tent’ state, mean­ing that they could turn into any type of adult cell. I could take a skin cell from your arm, use these genes to turn it into a pluripo­tent stem cell, and then ‘dif­fer­en­ti­ate’ that stem cell into any kind of cell I liked.

Yamana­ka received the Nobel Prize in 2012 for this dis­cov­ery, and it was around this time that we realised quite how exten­sive­ly this process of induc­ing pluripo­ten­cy turns back the clock in cells. Not only does it wind back the devel­op­men­tal clock, revert­ing the cell to a pluripo­tent state, but it also seems to reduce the bio­log­i­cal age of the cells, mak­ing them younger and health­i­er in a num­ber of dif­fer­ent ways.

Turn­ing all our cells into stem cells would be a ter­ri­ble idea — I’m quite fond of my brain cells being brain cells, thanks very much — but the good news is, if you acti­vate the Yamana­ka fac­tors inter­mit­tent­ly rather than con­tin­u­ous­ly, a cell can shed a few years of bio­log­i­cal age with­out turn­ing into a dif­fer­ent kind of cell⁹. Doing exact­ly this has been shown to improve the health of mice with a dis­ease that caus­es them to age pre­ma­ture­ly, and regen­er­ate tis­sues in adult mice that would nor­mal­ly only heal prop­er­ly before birth, not in an adult mouse.

The promise of this approach made head­lines when bil­lion­aires includ­ing Ama­zon founder Jeff Bezos cre­at­ed a $3bn start­up called Altos Labs¹⁰ and recruit­ed a num­ber of the top sci­en­tists work­ing on repro­gram­ming, includ­ing Yamana­ka, to work on turn­ing this idea from great news for mice, to great news for peo­ple. The ques­tion is whether we can move this from a phe­nom­e­non observed in genet­i­cal­ly mod­i­fied mice in the lab to us unmod­i­fied humans walk­ing around in the wild—and $3bn may just be enough to find out.