03.2020 | THE SCIENTIST 45could be adverse consequences from kill-
ing senescent cells. If cells, even those in a
state of senescence, die in large numbers
at once, they could spill intracellular con-
tents into surrounding tissue, potentially
causing organ dysfunction—a phenom-
enon observed in some cancer patients
during harsh treatments. This concern is
compounded by the idea that the immune
systems of older people may not be effi-
cient enough to clear the cellular waste
generated by killing senescent cells.^20
Both the Unity and Mayo teams consider
the chances of these issues occurring to be
low, given the relatively low numbers of
senescent cells in individual tissues. Unity
researchers estimate that less than 7 per-
cent of cells in tissue biopsies of osteoar-
thritis patients’ knees are senescent.
Campisi, meanwhile, wonders about
the consequences of losing the benefits
that senescent cells provide. Of the hun-
dreds of proteins secreted by these cells
that her group has identified over the
years, some are critical for wound heal-
ing, for instance—eliminate them all,
and the body’s ability to handle injuries
may suffer, she notes. “There will be
times where you’ll have to be cautious.
Yo u probably don’t want to take a seno-
lytic before you go into major surgery.”
Hopeful that they can overcome such
challenges, the Mayo Clinic and Unity
researchers are forging ahead. Kirkland
says his team has several more trials for
serious conditions, including osteoporo-
sis and Alzheimer’s disease, in the pipe-
line, and Unity is planning trials for age-
related eye diseases—such as macular
degeneration—with its other senolytic
compounds, UBX1967 and UBX1325.
Further in the future, the researchers
hope to explore the possibility of seno-
lytic drugs as prophylactics to help peo-
ple who are healthy, but who have high
levels of senescent cells, to delay the
onset of physical decline and disease.
Campisi, Kirkland, and Unity
researchers are quick to caution against
going down that road too quickly. Some
in the anti-aging industry have already
jumped at the prospect of marketing
supplements like quercetin as newfound
elixirs of youth. But “people should not
be taking these drugs until there’s really
clear evidence from Phase 2 trials that
they’re safe and effective,” says Kirk-
land—“and that may or may not be true.”
While early clinical trials of senolyt-
ics as anti-aging drugs are generating
guarded excitement, aging researchers
are still trying to figure out the role of
cellular senescence in the fundamental
aging process. Although it’s not in ques-
tion that senescence is a driver of aging,
it’s certainly not the only one, or even
a major one, Campisi says. If it were,
researchers would be able to make mice
live much longer by eliminating senes-
cent cells, but that isn’t the case. Exper-
iments by Kirkland and van Deursen
have increased rodents’ median lifes-
pan—meaning that fewer of the ani-
mals are dying young—but eliminating
senescent cells couldn’t extend the max-
imum lifespan of the animals.
“We have no evidence that this strat-
egy—or any strategy—will extend abso-
lute years of life,” Campisi says, “but
it’s extending years of healthy life that
might be on the horizon—if these drugs
work out in the clinic.” gKatarina Zimmer is a New York–based
freelance journalist. Find her on Twitter
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I think that our
possibilities of
translation are
pretty high.
—Felipe Sierra, National Institute on Aging