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January 23, 2020 - Image 2

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The Michigan Daily

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Exciting news for exercise
Exciting news for exercise

enthusiasts and casual gym-
enthusiasts and casual gym-
goers:
researchers
at
the
goers:
researchers
at
the

University of Michigan have
University of Michigan have
found a protein called Sestrin
found a protein called Sestrin
that has the potential to induce
that has the potential to induce
some of the most positive effects
some of the most positive effects
of exercise without any training
of exercise without any training
or conditioning.
or conditioning.

The laboratory of Jun Hee
The laboratory of Jun Hee

Lee, an associate professor
Lee, an associate professor
of molecular and integrative
of molecular and integrative
physiology, is conducting the
physiology, is conducting the
research. His work focuses
research. His work focuses
on Sestrin, which is produced
on Sestrin, which is produced
naturally by cells in response to
naturally by cells in response to
various environmental stresses,
various environmental stresses,
including exercise.
including exercise.

In the future, researchers
In the future, researchers

hope the protein can be used
hope the protein can be used
to combat muscle decline in
to combat muscle decline in
the elderly or people who are
the elderly or people who are
immobile.
immobile.

According to Lee, previous
According to Lee, previous

research has shown that Sestrin
research has shown that Sestrin
is linked to metabolism and his
is linked to metabolism and his
lab has been investigating its
lab has been investigating its
role in different stress responses
role in different stress responses
for more than 10 years. Recently,
for more than 10 years. Recently,
research into the protein has
research into the protein has
linked it to the benefits of
linked it to the benefits of
exercise-induced stress.
exercise-induced stress.

“It has been known that this
“It has been known that this

protein has various metabolic
protein has various metabolic
functions, so our idea was
functions, so our idea was
that this protein somehow can
that this protein somehow can
connect how cells respond to
connect how cells respond to
different stresses, so we have
different stresses, so we have
been studying this molecule in
been studying this molecule in
various stress contexts,” Lee
various stress contexts,” Lee
said. “It is known that exercise
said. “It is known that exercise
induces physical and oxidative
induces physical and oxidative
stress inside muscles, so we
stress inside muscles, so we
thought that maybe Sestrin, as
thought that maybe Sestrin, as
a stress response molecule, can
a stress response molecule, can
be beneficial for organisms.”
be beneficial for organisms.”

Lee said previous research
Lee said previous research

demonstrated exercise training
demonstrated exercise training
increases synthesis of Sestrin.
increases synthesis of Sestrin.
His team tested this idea in fruit
His team tested this idea in fruit
flies as well.
flies as well.

“We saw more Sestrin after
“We saw more Sestrin after

exercise,”
Lee
said.
“Our
exercise,”
Lee
said.
“Our

research showed that more
research showed that more
physical activity increases the
physical activity increases the
Sestrin and no physical activity
Sestrin and no physical activity
decreases the Sestrin.”
decreases the Sestrin.”

Lee’s lab also collaborated with
Lee’s lab also collaborated with

researchers in Spain to investigate
researchers in Spain to investigate
the potential role of Sestrin in
the potential role of Sestrin in
muscle atrophy as people age.
muscle atrophy as people age.

“When we performed those
“When we performed those

studies in flies and mice we also
studies in flies and mice we also
had a chance to collaborate with
had a chance to collaborate with
a Spanish school who actually
a Spanish school who actually
focused on the muscle-wasting
focused on the muscle-wasting
condition, so their focus is
condition, so their focus is
muscle
atrophy,”
Lee
said.
muscle
atrophy,”
Lee
said.

“What they found is whenever
“What they found is whenever
they immobilize the muscle …
they immobilize the muscle …
they see this Sestrin protein
they see this Sestrin protein
expression is diminished.”
expression is diminished.”

Lee said the collaborators
Lee said the collaborators

found a correlation between
found a correlation between
induced Sestrin expression and
induced Sestrin expression and
preventing muscle loss in aging
preventing muscle loss in aging
populations.
populations.

“(Sestrin) very dramatically
“(Sestrin) very dramatically

attenuated muscle loss during
attenuated muscle loss during
disuse and even after aging,”
disuse and even after aging,”
Lee said. “So combined with
Lee said. “So combined with
these two stories we think
these two stories we think
that
Sestrin
plays
a
very
that
Sestrin
plays
a
very

important
role
in
muscle
important
role
in
muscle

biology, especially in the focus
biology, especially in the focus
of physical movement.”
of physical movement.”

LSA senior Eric Mettetal worked
LSA senior Eric Mettetal worked

in Lee’s lab for two years and
in Lee’s lab for two years and
contributed to this project. Mettetal
contributed to this project. Mettetal
said it is important to understand
said it is important to understand
the mechanisms behind Sestrin
the mechanisms behind Sestrin
expression now that its potential
expression now that its potential
benefits are known.
benefits are known.

“Understanding
the
“Understanding
the

mechanisms will help us learn
mechanisms will help us learn
ways of potential therapeutic
ways of potential therapeutic

approaches
in
the
future,”
approaches
in
the
future,”

Mettetal
said.
“If
Sestrin
Mettetal
said.
“If
Sestrin

has been shown to be this
has been shown to be this
important component of how
important component of how
our body responds positively
our body responds positively
with regards to exercise and if
with regards to exercise and if
Sestrin has all these beneficial
Sestrin has all these beneficial
effects regarding metabolism,
effects regarding metabolism,
if we can find a way to harness
if we can find a way to harness
the power of Sestrin in a sense
the power of Sestrin in a sense
and its therapeutic potential,
and its therapeutic potential,
this could have really great
this could have really great
implications
for
potential
implications
for
potential

therapies in the future.”
therapies in the future.”

Lee
said
he
planned
to
Lee
said
he
planned
to

uncover these mechanisms of
uncover these mechanisms of
Sestrin expression now that
Sestrin expression now that
their benefits are so clear.
their benefits are so clear.

“It is very exciting because
“It is very exciting because

just by altering this singular
just by altering this singular
gene and protein we were able
gene and protein we were able
to recapitulate many of the
to recapitulate many of the
benefits of exercise,” Lee said.
benefits of exercise,” Lee said.
“Our goal is to understand
“Our goal is to understand
how this protein synthesis is
how this protein synthesis is
regulated and how this protein
regulated and how this protein
activity
is
regulated

by
activity
is
regulated

by

exercise or maybe in the future
exercise or maybe in the future
pharmacologically.”
pharmacologically.”

Lee and his team investigated
Lee and his team investigated

the specific effects Sestrin has
the specific effects Sestrin has
on exercise ability by creating
on exercise ability by creating
two types of flies: a Sestrin
two types of flies: a Sestrin
knockout that produced no
knockout that produced no
protein
and
another
which
protein
and
another
which

upregulated Sestrin production
upregulated Sestrin production
automatically without exercise.
automatically without exercise.

These
flies
were
then
These
flies
were
then

exercised the same way as the
exercised the same way as the
normal wild-type group, the
normal wild-type group, the
phenotype of the fly’s natural
phenotype of the fly’s natural
form. The Sestrin knockouts
form. The Sestrin knockouts
demonstrated
no
improved
demonstrated
no
improved

endurance over time compared
endurance over time compared
to normal flies.
to normal flies.

“We put them on the same
“We put them on the same

exercise scheme,” Lee said, “but
exercise scheme,” Lee said, “but
exercise didn’t have benefits
exercise didn’t have benefits
for these knockout flies … they
for these knockout flies … they
don’t improve endurance after
don’t improve endurance after

training.”
training.”

Lee said flies that were
Lee said flies that were

engineered
to
overproduce
engineered
to
overproduce

Sestrin
out-performed
well-
Sestrin
out-performed
well-

conditioned normal flies, even
conditioned normal flies, even
before they underwent specific
before they underwent specific
exercise training.
exercise training.

“When
we
expressed
this
“When
we
expressed
this

protein inside flies, first we had
protein inside flies, first we had
full body expression, and then
full body expression, and then
we found that even without
we found that even without
exercise they were performing
exercise they were performing
much better,” Lee said. “When
much better,” Lee said. “When
it is overexpressed in muscles
it is overexpressed in muscles
specifically it was producing
specifically it was producing
exercise,
like
extension
of
exercise,
like
extension
of

endurance.”
endurance.”

Lee said his team then studied
Lee said his team then studied

Sestrin in mice, using wild-type
Sestrin in mice, using wild-type
mice and mice that did not have
mice and mice that did not have
Sestrin. Lee elaborated on the
Sestrin. Lee elaborated on the
metabolic effects exercise has
metabolic effects exercise has
on normal mice and how a lack
on normal mice and how a lack
of Sestrin severely diminishes
of Sestrin severely diminishes
these effects.
these effects.

“After
endurance
exercise
“After
endurance
exercise

training
the
(normal
mice)
training
the
(normal
mice)

are consuming oxygen in a
are consuming oxygen in a
more efficient way,” Lee said.
more efficient way,” Lee said.
“They are burning fat … only
“They are burning fat … only
after
vigorous
exercise
do
after
vigorous
exercise
do

they burn glucose, but these
they burn glucose, but these
Sestrin-deficient mice actually
Sestrin-deficient mice actually
have problems in that kind of
have problems in that kind of
switching, so even when they
switching, so even when they
are walking they cannot burn
are walking they cannot burn
the fat, they use glucose.”
the fat, they use glucose.”

Myungjin
Kim,
a
research
Myungjin
Kim,
a
research

assistant
professor
in
the
assistant
professor
in
the

department of molecular and
department of molecular and
integrative physiology, contributed
integrative physiology, contributed
to this project. Kim said the
to this project. Kim said the
researchers had to incentivize
researchers had to incentivize
exercise as part of the regiment
exercise as part of the regiment
with mice and found a lack of
with mice and found a lack of
Sestrin hinders exercise ability.
Sestrin hinders exercise ability.

2 — Thursday, January 23, 2020
The Michigan Daily — michigandaily.com
News

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annika @nnikawang
will never forget how
freshman year at umich uhs
i was told i had allergies and
when i went to my home to
my primary care he said “you
have bronchitis and a sinus
infection as well as a minor
case of tonsillitis”

RDAN @sweaty_grl
do student athletes know
they can take their umich
coats off?? serious question.

Kiernan @voidamoeba
why is umich so obsessed
with forcing everyone to have
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what, am i supposed to be
afraid of all of the people trying
to log into my canvas account
to read class syllabi??

Brian @brianthatoneguy
umich on the weekends be
like “oh you like eating lunch?
name every dining hall that
serves lunch. trick question.
they’re all closed. Starve.”

em @emilylevy1414
just had to explain to my bf,
who has attended UMich
for 3 years, what the Hill
Auditorium was🥰

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‘U’ researchers produce effects
of exercise using protein Sestrin

In the future, physiology lab hopes research discoveries can be used
to combat muscle decline in the elderly, people who are immobile

HANNAH MACKAY
Daily Staff Reporter

:-) @kaixxxisa
Ann Arbor hipsters are worse
than New York hipsters
because Ann Arbor hipsters
think they’re an oppressed
minority for wearing a
Fjallraven backpack and
thrifted clothes

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