Science - USA (2021-10-29)

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528 29 OCTOBER 2021 • VOL 374 ISSUE 6567 science.org SCIENCE

THERE’S NO QUESTION that sleep benefits
the brain in creatures that have one (see
p. 550). It helps the brain consolidate
memories and flush out toxic waste. It may
also help the brain stay plastic by pruning
and strengthening connections between
nerve cells.
But if animals without brains need
sleep, those functions can’t be the whole
story, Sehgal says. “Given that sleep is
so widely conserved, it likely serves a
fundamental function to preserve basic
physiological processes.”
Some recent clues from brainless ani-
mals suggest sleep factors into energy bal-
ance and metabolism. Raizen’s team has
found the much-studied roundworm Cae-
norhabditis elegans only naps when meta-
bolic demands are high. The larvae go limp
for 1 or 2 hours when they
are molting and replacing
their exoskeletons, or when
excess heat or ultraviolet
(UV) light causes stress. An
enzyme called salt-inducible
kinase 3 provides a direct
link between sleep and me-
tabolism. Known to help reg-
ulate sleep in mammals, it
also mobilizes fat stores in C.
elegans to boost the worm’s

energy levels. In hydra, too, Itoh’s team has

found a gene that both regulates metabo-

lism and influences sleep.

Deprivation studies also point to sleep’s

metabolic role. Sehgal has found fruit flies

carrying a mutation that reduces their

sleep are less able to metabolize nitrogen,

which means they may have trouble break-

ing down and rebuilding proteins and pro-

cessing waste. The result is a buildup of

charged molecules called polyamines that

can damage DNA and RNA, Sehgal’s team

reported on 2 October on bioRxiv. “When

we are sleep-deprived, it’s not just brain

function that is affected,” she says.

Sleep deprivation also appears to attack

the gut in fruit flies and mice, by leading

to a buildup of harmful molecules known

as reactive oxygen species, Harvard Medi-

cal School biologist Dragana Rogulja and

colleagues reported last year in Cell. Some-

how, that accumulation leads to early death

in both species, the team found. Rogulja

suspects the gut, among the first organs to

evolve in multicellular animals, was one of

the original beneficiaries of sleep, and that

“a lot of [sleep’s] additional roles evolved

as animals become more complex.”

To get to the essence of why animals

sleep, however, requires studying it in spe-

cies so simple they don’t even have a gut.

Raizen decided to look at placozoans—

round, flat, transparent creatures no bigger

than a sesame seed that have just two layers

of cells, each outfitted with whiplike projec-

tions called cilia. Placozoans lack nerve cells;

their cells communicate via chemical secre-

tions that control cilia movements. Outside

of parasites that live attached

to other life forms, placozoans

“are the simplest animals on

Earth,” says Carolyn Smith, a

neuroscientist at the National

Institute of Neurological Dis-

orders and Stroke who has

studied them for more than

10 years.

Placozoans use their cilia

to crawl randomly along

rocks at the tideline until CREDITS: (PHOTO JAMES JAGGARD, PHILIPPE MOURRAIN, ADAM DOUGLASS, AND ADRIADNE PENALVA; (GRAPHIC N. DESAI/

SCIENCE

Physical

quiescence

Placozoan Sponge Hydra Jellyfish Roundworm Octopus Fruit y Sea slug Crayfish Fish

Typical posture

or sleep place

Less responsive

to stimuli

Can rapidly

wake up

Makes up for

lost sleep

Aected by

sleep drugs

Changes in brain

or cellular activity

Conservation

of genes

Follows circadian

regulation

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The see-through fish Danionella translucida may help reveal how the body controls sleep.

The signs of sleep
By looking broadly for behaviors characterizing sleep in humans and other organisms, researchers are finding that most animals, even very simple ones, have a restful state.
How well each creature satisfies these criteria is controversial, but the work is expanding our understanding of the role and control of sleep, even in humans.