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Subject: Fwd: MOTS-c & Morning Workout Timing =?utf-8?Q?=E2=80=94_?=A
 Beginner-Friendly Breakdown
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---------- =46orwarded message ----------
=46rom: Derek from Peptide Price <derekpruski=40substack.com>
Date: Mar 21, 2026 at 8:24=E2=80=AFAM -0400
To: tjphuhs=40gmail.com
Subject: MOTS-c & Morning Workout Timing =E2=80=94 A Beginner-=46riendly =
Breakdown

> Not medical advice, not personal advice.
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> =46orwarded this email=3F Subscribe here for more
> MOTS-c & Morning Workout Timing =E2=80=94 A Beginner-=46riendly Breakdo=
wn
> Derek
> Mar 21
>
> READ IN APP
>
> Not medical advice, not personal advice. =46or educational purposes onl=
y. All use cases discussed are strictly research use only.
> If a researcher is using MOTS-c and also hitting the gym in the morning=
, timing matters. Here=E2=80=99s why =E2=80=94 broken down in plain langu=
age.
> =46irst, What Is MOTS-c=3F
> MOTS-c is a small peptide encoded in mitochondrial DNA, which makes it =
unique among peptides. Most peptides are encoded in the cell=E2=80=99s nu=
cleus. Mitochondria are the energy-producing organelles inside your cells=
 =E2=80=94 often called the =E2=80=9Cpowerhouse of the cell.=E2=80=9D MOT=
S-c is essentially a signal that mitochondria send out to communicate wit=
h the rest of the body about energy status.
> In research, it has shown strong effects on metabolism, insulin sensiti=
vity, fat utilization, and cellular energy regulation.
> Two Pathways You Need to Understand
> To understand why timing matters, a researcher needs to understand two =
opposing biological pathways. Think of them like two switches in the body=
 that generally can=E2=80=99t both be fully on at the same time.
> AMPK =E2=80=94 The Low =46uel Switch
> AMPK stands for adenosine monophosphate-activated protein kinase. Just =
think of it as the body=E2=80=99s low-energy alarm system. When cellular =
energy is running low =E2=80=94 during fasting, cardio, or caloric restri=
ction =E2=80=94 AMPK activates. Once on, it tells the body to:
>
> =E2=80=A2 > Burn fat for fuel
> =E2=80=A2 > Improve how cells use glucose
> =E2=80=A2 > Build new mitochondria
> =E2=80=A2 > Conserve energy by slowing down expensive biological proces=
ses =E2=80=94 including building new muscle tissue
>
> MOTS-c is a potent AMPK activator. That=E2=80=99s largely where its met=
abolic benefits originate.
> mTOR =E2=80=94 The Build and Grow Switch
> mTOR stands for mechanistic target of rapamycin. Think of this as the b=
ody=E2=80=99s anabolic =E2=80=94 or growth =E2=80=94 signal. When mTOR is=
 activated, the body ramps up muscle protein synthesis, drives hypertroph=
y (muscle growth), and invests resources into repair and building.
> Resistance training is one of the most powerful ways to stimulate mTOR.=
 Eating adequate protein and carbohydrates after training also helps keep=
 it elevated.
> Why They Conflict
> Here=E2=80=99s the key point: AMPK and mTOR are opposing signals. When =
AMPK is highly active, it puts the brakes on mTOR. Biologically this make=
s sense =E2=80=94 the body doesn=E2=80=99t want to be building expensive =
new muscle tissue when it thinks it=E2=80=99s in an energy-deficient stat=
e. These two pathways actively suppress each other, which is why administ=
ering a potent AMPK activator right before resistance training creates a =
potential conflict worth thinking about.
> The Important Nuance
> Before getting into scenarios, this needs to be stated clearly because =
it gets misunderstood constantly.
> Activating AMPK does not completely shut off mTOR. It does not eliminat=
e muscle growth.
> The relationship between these two pathways is nuanced =E2=80=94 it dep=
ends on how strongly each is activated, the researcher=E2=80=99s nutritio=
n status, training intensity, recovery, and a range of other factors. A r=
esearch subject is not going to lose all their gains because MOTS-c was a=
dministered before a workout. The effect is more of a partial dampening u=
nder certain conditions, not a complete block.
> There=E2=80=99s also a compelling wrinkle specific to MOTS-c: research =
has shown it can suppress myostatin. Myostatin is a protein the body prod=
uces that actively limits how much muscle can grow =E2=80=94 it functions=
 as a biological brake on muscle development. Lower myostatin means that =
brake is loosened, which can support greater skeletal muscle growth poten=
tial.
> Whether this effect is enough to fully offset any mTOR dampening from A=
MPK activation is still an open research question =E2=80=94 but it makes =
the picture considerably more complex than simply writing off MOTS-c as c=
ounterproductive to muscle growth.
> Scenario 1 =E2=80=94 The Optimal Approach (If Schedule Allows)
> This is the approach that theoretically extracts the most from both MOT=
S-c and resistance training by keeping the two signals separated.
> Step 1 =E2=80=94 Administer MOTS-c fasted, first thing in the morning.
> Step 2 =E2=80=94 =46ollow with low-to-moderate intensity movement. A wa=
lk, steady state cardio, a light bike ride. Not resistance training. In a=
 fasted state with low-intensity activity, AMPK is heavily biased and sub=
strate availability is low =E2=80=94 the body is primed to respond to MOT=
S-c=E2=80=99s metabolic signals. This is the environment where its effect=
s on mitochondrial function, fat oxidation, glucose metabolism, and metab=
olic flexibility are operating at full capacity with no interference.
> Step 3 =E2=80=94 Remain in a fasted or semi-fasted state for roughly 2=E2=
=80=934 hours. This gives the acute AMPK signaling window time to normali=
ze.
> Step 4 =E2=80=94 Break the fast with a solid meal. Protein, carbohydrat=
es, adequate calories. This refuels glycogen stores, raises circulating a=
mino acid availability, and shifts the hormonal environment toward anabol=
ism.
> Step 5 =E2=80=94 Train. With MOTS-c out of the acute signaling window a=
nd the body adequately refueled, resistance training can potently stimula=
te mTOR without meaningful AMPK interference. The anabolic response to tr=
aining is uncompromised.
> The end result is two clean, well-supported signaling environments =E2=80=
=94 one optimized for metabolic and mitochondrial adaptation in the morni=
ng, one optimized for muscle growth later in the day. Both get their mome=
nt.
> Scenario 2 =E2=80=94 Morning Administration Before Resistance Training
> Not every researcher has the schedule flexibility for Scenario 1, and t=
hat=E2=80=99s completely fine.
> =46or a researcher who can only train in the morning: administer MOTS-c=
, train, and don=E2=80=99t overthink it.
> The mechanistic concern around AMPK and mTOR is real, but it is not cat=
astrophic in a practical context. The research subject is still going to =
produce a meaningful training stimulus, still going to drive muscle prote=
in synthesis, and still going to see adaptation over time. The myostatin =
suppression effect from MOTS-c also adds a layer that may partially compe=
nsate for any attenuation of mTOR signaling.
> Compared to Scenario 1, outcomes on the muscle growth side may be margi=
nally less optimal =E2=80=94 but results are still being produced on both=
 fronts. This is not a failure mode. It is a practical, workable approach=
 for researchers whose schedules demand it.
> The Simple Version
> Maximum benefit: Administer MOTS-c fasted in the morning, do light card=
io, eat a solid meal a few hours later, then train.
> Constrained schedule: Administer MOTS-c and train in the morning anyway=
. Still worth it.
> =46or research use only, not for human consumption. This is not medical=
 advice or personal advice =E2=80=94 strictly educational.
> I want to give a huge shoutout to Coach Cam because he provided a lot o=
f different perspectives on this through his research as well.
> Questions or thoughts=3F Drop them in the comments.
> Upgrade to paid
> You're currently a free subscriber to Peptide Price. =46or the full exp=
erience, upgrade your subscription.
> Upgrade to paid
>
> Share
>
>
> Like
> Comment
> Restack
>
> =C2=A9 2026 Derek Pruski
> 548 Market Street PMB 72296, San =46rancisco, CA 94104
> Unsubscribe

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<div name=3D=22messageReplySection=22>---------- =46orwarded message ----=
------<br />
<b>=46rom:</b> Derek from Peptide Price &lt;derekpruski=40substack.com&gt=
;<br />
<b>Date:</b> Mar 21, 2026 at 8:24=E2=80=AFAM -0400<br />
<b>To:</b> tjphuhs=40gmail.com<br />
<b>Subject:</b> MOTS-c &amp; Morning Workout Timing =E2=80=94 A Beginner-=
=46riendly Breakdown<br />
<br />
<blockquote type=3D=22cite=22><img src=3D=22https://eotrx.substackcdn.com=
/open=3Ftoken=3DeyJtIjoiPDIwMjYwMzIxMTIyNDIwLjMuM2Q3NWQ5ZTM3ZDU4M2RlN0BtZ=
y1kMC5zdWJzdG=46jay5jb20-IiwidSI6MjczNjIyMzk4LCJyIjoidGpwaHVoc0BnbW=46pbC=
5jb20iLCJkIjoibWctZDAuc3Vic3RhY2suY29tIiwicCI6MTkxNjY3OTk2LCJ0IjoibmV3c2x=
ldHRlciIsImEiOiJldmVyeW9uZSIsInMiOjMzNjUzNjcsImMiOiJwb3N0IiwiZiI6dHJ1ZSwi=
cG9zaXRpb24iOiJ0b3AiLCJpYXQiOjE3NzQwOTU4NjQsImV4cCI6MTc3NjY4Nzg2NCwiaXNzI=
joicHViLTAiLCJzdWIiOiJlbyJ9.RBgZZ-pGn2T581pXUbi33fQBHVWGzgpA2iP3z=46878uc=
=22 alt=3D=22=22 width=3D=221=22 height=3D=221=22 border=3D=220=22 style=3D=
=22height:1px =21important;width:1px =21important;border-width:0 =21impor=
tant;margin-top:0 =21important;margin-bottom:0 =21important;margin-right:=
0 =21important;margin-left:0 =21important;padding-top:0 =21important;padd=
ing-bottom:0 =21important;padding-right:0 =21important;padding-left:0 =21=
important;=22 />
<div class=3D=22preview=22 style=3D=22display:none;font-size:1px;color:=23=
333333;line-height:1px;max-height:0px;max-width:0px;opacity:0;overflow:hi=
dden;=22>Not medical advice, not personal advice.</div>
<div class=3D=22preview=22 style=3D=22display:none;font-size:1px;color:=23=
333333;line-height:1px;max-height:0px;max-width:0px;opacity:0;overflow:hi=
dden;=22>=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23=
160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=
=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD=
=CD=8F &=23160; =E2=80=87 =C2=AD=CD=8F &=23160; =E2=80=87 =C2=AD</div>
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https://open.substack.com/pub/derekpruski/p/mots-c-and-morning-workout-ti=
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ight: 500;border: 1px solid rgb(0,0,0,.1);border-radius: 9999px;text-tran=
sform: uppercase;font-size: 12px;line-height: 12px;padding: 9px 14px;text=
-decoration: none;color: rgb(119,119,119);=22>
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ight: 26px;display: inline-block;vertical-align: middle;max-width: 0;min-=
height: 18px;=22></div>
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argin-right: 4px=22>READ IN APP</span><img class=3D=22icon text-icon=22 s=
rc=3D=22https://substackcdn.com/image/fetch/=24s=5F=21ET-=5F=21,w=5F36,c=5F=
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<td height=3D=2216=22 style=3D=22font-size:0px;line-height:0;=22>&=23160;=
</td>
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<div class=3D=22post typography=22 dir=3D=22auto=22 style=3D=22--image-of=
fset-margin: -120px;padding: 32px 0 0 0;font-size: 16px;line-height: 26px=
;=22>
<div class=3D=22body markup=22 dir=3D=22auto=22 style=3D=22text-align: in=
itial;font-size: 16px;line-height: 26px;width: 100%;word-break: break-wor=
d;margin-bottom: 16px;=22>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;margin-top: 0;=22><em>Not medical advice, not personal adv=
ice. =46or educational purposes only. All use cases discussed are strictl=
y research use only.</em></p>
<div style=3D=22font-size: 16px;line-height: 26px;=22>
<hr style=3D=22margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,=
0,.1);border: none;=22 /></div>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>If a researcher is using MOTS-c and also hitting the g=
ym in the morning, timing matters. Here=E2=80=99s why =E2=80=94 broken do=
wn in plain language.</p>
<div class=3D=22captioned-image-container-static=22 style=3D=22font-size:=
 16px;line-height: 26px;margin: 32px auto;=22>
<figure style=3D=22width: 100%;margin: 0 auto;=22>
<table class=3D=22image-wrapper=22 width=3D=22100%=22 border=3D=220=22 ce=
llspacing=3D=220=22 cellpadding=3D=220=22 data-component-name=3D=22Image2=
ToDOMStatic=22 style=3D=22mso-padding-alt: 1em 0 1.6em;=22>
<tbody>
<tr>
<td style=3D=22text-align: center;=22></td>
<td class=3D=22content=22 align=3D=22left=22 width=3D=221456=22 style=3D=22=
text-align: center;=22><a class=3D=22image-link=22 target=3D=22=5Fblank=22=
 href=3D=22https://substack.com/redirect/d6baeeff-39df-4a22-bfb7-e176393e=
ac0e=3Fj=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Z=
s=22 rel=3D=22=22 style=3D=22position: relative;flex-direction: column;al=
ign-items: center;padding: 0;width: auto;height: auto;border: none;text-d=
ecoration: none;display: block;margin: 0;=22><img class=3D=22wide-image=22=
 data-attrs=3D=22=7B&quot;src&quot;:&quot;https://substack-post-media.s3.=
amazonaws.com/public/images/87862b7b-1ce5-45e4-9f52-ab548e11cec5=5F1536x1=
024.png&quot;,&quot;srcNoWatermark&quot;:null,&quot;fullscreen&quot;:null=
,&quot;imageSize&quot;:null,&quot;height&quot;:971,&quot;width&quot;:1456=
,&quot;resizeWidth&quot;:null,&quot;bytes&quot;:3000903,&quot;alt&quot;:n=
ull,&quot;title&quot;:null,&quot;type&quot;:&quot;image/png&quot;,&quot;h=
ref&quot;:null,&quot;belowThe=46old&quot;:false,&quot;topImage&quot;:true=
,&quot;internalRedirect&quot;:&quot;https://derekpruski.substack.com/i/19=
1667996=3Fimg=3Dhttps%3A%2=46%2=46substack-post-media.s3.amazonaws.com%2=46=
public%2=46images%2=4687862b7b-1ce5-45e4-9f52-ab548e11cec5=5F1536x1024.pn=
g&quot;,&quot;isProcessing&quot;:false,&quot;align&quot;:null,&quot;offse=
t&quot;:false=7D=22 alt=3D=22=22 width=3D=22550=22 height=3D=22366.792582=
4175824=22 src=3D=22https://substackcdn.com/image/fetch/=24s=5F=21eNnx=21=
,w=5F1100,c=5Flimit,f=5Fauto,q=5Fauto:good,fl=5Fprogressive:steep/https%3=
A%2=46%2=46substack-post-media.s3.amazonaws.com%2=46public%2=46images%2=46=
87862b7b-1ce5-45e4-9f52-ab548e11cec5=5F1536x1024.png=22 style=3D=22border=
: none =21important;vertical-align: middle;display: block;-ms-interpolati=
on-mode: bicubic;height: auto;margin-bottom: 0;width: auto =21important;m=
ax-width: 100% =21important;margin: 0 auto;=22 /></a></td>
<td style=3D=22text-align: center;=22></td>
</tr>
</tbody>
</table>
</figure>
</div>
<div style=3D=22font-size: 16px;line-height: 26px;=22>
<hr style=3D=22margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,=
0,.1);border: none;=22 /></div>
<h2 class=3D=22header-anchor-post=22 style=3D=22position: relative;font-f=
amily: 'S=46 Pro Display',-apple-system-headline,system-ui,-apple-system,=
BlinkMacSystem=46ont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit=
-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit=
-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);li=
ne-height: 1.16em;font-size: 1.625em;=22>=46irst, What Is MOTS-c=3F</h2>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>MOTS-c is a small peptide encoded in mitochondrial DNA=
, which makes it unique among peptides. Most peptides are encoded in the =
cell=E2=80=99s nucleus. Mitochondria are the energy-producing organelles =
inside your cells =E2=80=94 often called the =E2=80=9Cpowerhouse of the c=
ell.=E2=80=9D MOTS-c is essentially a signal that mitochondria send out t=
o communicate with the rest of the body about energy status.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>In research, it has shown strong effects on metabolism=
, insulin sensitivity, fat utilization, and cellular energy regulation.</=
p>
<div style=3D=22font-size: 16px;line-height: 26px;=22>
<hr style=3D=22margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,=
0,.1);border: none;=22 /></div>
<h2 class=3D=22header-anchor-post=22 style=3D=22position: relative;font-f=
amily: 'S=46 Pro Display',-apple-system-headline,system-ui,-apple-system,=
BlinkMacSystem=46ont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit=
-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit=
-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);li=
ne-height: 1.16em;font-size: 1.625em;=22>Two Pathways You Need to Underst=
and</h2>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>To understand why timing matters, a researcher needs t=
o understand two opposing biological pathways. Think of them like two swi=
tches in the body that generally can=E2=80=99t both be fully on at the sa=
me time.</p>
<h3 class=3D=22header-anchor-post=22 style=3D=22position: relative;font-f=
amily: 'S=46 Pro Display',-apple-system-headline,system-ui,-apple-system,=
BlinkMacSystem=46ont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit=
-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit=
-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);li=
ne-height: 1.16em;font-size: 1.375em;=22>AMPK =E2=80=94 The Low =46uel Sw=
itch</h3>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>AMPK stands for adenosine monophosphate-activated prot=
ein kinase. Just think of it as the body=E2=80=99s low-energy alarm syste=
m. When cellular energy is running low =E2=80=94 during fasting, cardio, =
or caloric restriction =E2=80=94 AMPK activates. Once on, it tells the bo=
dy to:</p>
<ul style=3D=22margin-top: 0;padding: 0;=22>
<li style=3D=22margin: 8px 0 0 32px;mso-special-format: bullet;=22>
<p style=3D=22color: rgb(54,55,55);line-height: 26px;margin-bottom: 0;box=
-sizing: border-box;padding-left: 4px;font-size: 16px;margin: 0;=22>Burn =
fat for fuel</p>
</li>
<li style=3D=22margin: 8px 0 0 32px;mso-special-format: bullet;=22>
<p style=3D=22color: rgb(54,55,55);line-height: 26px;margin-bottom: 0;box=
-sizing: border-box;padding-left: 4px;font-size: 16px;margin: 0;=22>Impro=
ve how cells use glucose</p>
</li>
<li style=3D=22margin: 8px 0 0 32px;mso-special-format: bullet;=22>
<p style=3D=22color: rgb(54,55,55);line-height: 26px;margin-bottom: 0;box=
-sizing: border-box;padding-left: 4px;font-size: 16px;margin: 0;=22>Build=
 new mitochondria</p>
</li>
<li style=3D=22margin: 8px 0 0 32px;mso-special-format: bullet;=22>
<p style=3D=22color: rgb(54,55,55);line-height: 26px;margin-bottom: 0;box=
-sizing: border-box;padding-left: 4px;font-size: 16px;margin: 0;=22>Conse=
rve energy by slowing down expensive biological processes =E2=80=94 inclu=
ding building new muscle tissue</p>
</li>
</ul>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>MOTS-c is a potent AMPK activator. That=E2=80=99s larg=
ely where its metabolic benefits originate.</p>
<h3 class=3D=22header-anchor-post=22 style=3D=22position: relative;font-f=
amily: 'S=46 Pro Display',-apple-system-headline,system-ui,-apple-system,=
BlinkMacSystem=46ont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit=
-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit=
-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);li=
ne-height: 1.16em;font-size: 1.375em;=22>mTOR =E2=80=94 The Build and Gro=
w Switch</h3>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>mTOR stands for mechanistic target of rapamycin. Think=
 of this as the body=E2=80=99s anabolic =E2=80=94 or growth =E2=80=94 sig=
nal. When mTOR is activated, the body ramps up muscle protein synthesis, =
drives hypertrophy (muscle growth), and invests resources into repair and=
 building.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>Resistance training is one of the most powerful ways t=
o stimulate mTOR. Eating adequate protein and carbohydrates after trainin=
g also helps keep it elevated.</p>
<h3 class=3D=22header-anchor-post=22 style=3D=22position: relative;font-f=
amily: 'S=46 Pro Display',-apple-system-headline,system-ui,-apple-system,=
BlinkMacSystem=46ont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit=
-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit=
-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);li=
ne-height: 1.16em;font-size: 1.375em;=22>Why They Conflict</h3>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>Here=E2=80=99s the key point: AMPK and mTOR are opposi=
ng signals. When AMPK is highly active, it puts the brakes on mTOR. Biolo=
gically this makes sense =E2=80=94 the body doesn=E2=80=99t want to be bu=
ilding expensive new muscle tissue when it thinks it=E2=80=99s in an ener=
gy-deficient state. These two pathways actively suppress each other, whic=
h is why administering a potent AMPK activator right before resistance tr=
aining creates a potential conflict worth thinking about.</p>
<div style=3D=22font-size: 16px;line-height: 26px;=22>
<hr style=3D=22margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,=
0,.1);border: none;=22 /></div>
<h2 class=3D=22header-anchor-post=22 style=3D=22position: relative;font-f=
amily: 'S=46 Pro Display',-apple-system-headline,system-ui,-apple-system,=
BlinkMacSystem=46ont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit=
-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit=
-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);li=
ne-height: 1.16em;font-size: 1.625em;=22>The Important Nuance</h2>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>Before getting into scenarios, this needs to be stated=
 clearly because it gets misunderstood constantly.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><strong>Activating AMPK does not completely shut off m=
TOR. It does not eliminate muscle growth.</strong></p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>The relationship between these two pathways is nuanced=
 =E2=80=94 it depends on how strongly each is activated, the researcher=E2=
=80=99s nutrition status, training intensity, recovery, and a range of ot=
her factors. A research subject is not going to lose all their gains beca=
use MOTS-c was administered before a workout. The effect is more of a par=
tial dampening under certain conditions, not a complete block.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>There=E2=80=99s also a compelling wrinkle specific to =
MOTS-c: research has shown it can suppress myostatin. Myostatin is a prot=
ein the body produces that actively limits how much muscle can grow =E2=80=
=94 it functions as a biological brake on muscle development. Lower myost=
atin means that brake is loosened, which can support greater skeletal mus=
cle growth potential.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>Whether this effect is enough to fully offset any mTOR=
 dampening from AMPK activation is still an open research question =E2=80=
=94 but it makes the picture considerably more complex than simply writin=
g off MOTS-c as counterproductive to muscle growth.</p>
<div style=3D=22font-size: 16px;line-height: 26px;=22>
<hr style=3D=22margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,=
0,.1);border: none;=22 /></div>
<h2 class=3D=22header-anchor-post=22 style=3D=22position: relative;font-f=
amily: 'S=46 Pro Display',-apple-system-headline,system-ui,-apple-system,=
BlinkMacSystem=46ont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit=
-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit=
-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);li=
ne-height: 1.16em;font-size: 1.625em;=22>Scenario 1 =E2=80=94 The Optimal=
 Approach (If Schedule Allows)</h2>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>This is the approach that theoretically extracts the m=
ost from both MOTS-c and resistance training by keeping the two signals s=
eparated.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><strong>Step 1</strong> <span>=E2=80=94 Administer MOT=
S-c fasted, first thing in the morning.</span></p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><strong>Step 2</strong> <span>=E2=80=94 =46ollow with =
low-to-moderate intensity movement. A walk, steady state cardio, a light =
bike ride. Not resistance training. In a fasted state with low-intensity =
activity, AMPK is heavily biased and substrate availability is low =E2=80=
=94 the body is primed to respond to MOTS-c=E2=80=99s metabolic signals. =
This is the environment where its effects on mitochondrial function, fat =
oxidation, glucose metabolism, and metabolic flexibility are operating at=
 full capacity with no interference.</span></p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><strong>Step 3</strong> <span>=E2=80=94 Remain in a fa=
sted or semi-fasted state for roughly 2=E2=80=934 hours. This gives the a=
cute AMPK signaling window time to normalize.</span></p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><strong>Step 4</strong> <span>=E2=80=94 Break the fast=
 with a solid meal. Protein, carbohydrates, adequate calories. This refue=
ls glycogen stores, raises circulating amino acid availability, and shift=
s the hormonal environment toward anabolism.</span></p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><strong>Step 5</strong> <span>=E2=80=94 Train. With MO=
TS-c out of the acute signaling window and the body adequately refueled, =
resistance training can potently stimulate mTOR without meaningful AMPK i=
nterference. The anabolic response to training is uncompromised.</span></=
p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>The end result is two clean, well-supported signaling =
environments =E2=80=94 one optimized for metabolic and mitochondrial adap=
tation in the morning, one optimized for muscle growth later in the day. =
Both get their moment.</p>
<div style=3D=22font-size: 16px;line-height: 26px;=22>
<hr style=3D=22margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,=
0,.1);border: none;=22 /></div>
<h2 class=3D=22header-anchor-post=22 style=3D=22position: relative;font-f=
amily: 'S=46 Pro Display',-apple-system-headline,system-ui,-apple-system,=
BlinkMacSystem=46ont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit=
-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit=
-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);li=
ne-height: 1.16em;font-size: 1.625em;=22>Scenario 2 =E2=80=94 Morning Adm=
inistration Before Resistance Training</h2>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>Not every researcher has the schedule flexibility for =
Scenario 1, and that=E2=80=99s completely fine.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>=46or a researcher who can only train in the morning: =
administer MOTS-c, train, and don=E2=80=99t overthink it.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>The mechanistic concern around AMPK and mTOR is real, =
but it is not catastrophic in a practical context. The research subject i=
s still going to produce a meaningful training stimulus, still going to d=
rive muscle protein synthesis, and still going to see adaptation over tim=
e. The myostatin suppression effect from MOTS-c also adds a layer that ma=
y partially compensate for any attenuation of mTOR signaling.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>Compared to Scenario 1, outcomes on the muscle growth =
side may be marginally less optimal =E2=80=94 but results are still being=
 produced on both fronts. This is not a failure mode. It is a practical, =
workable approach for researchers whose schedules demand it.</p>
<div style=3D=22font-size: 16px;line-height: 26px;=22>
<hr style=3D=22margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,=
0,.1);border: none;=22 /></div>
<h2 class=3D=22header-anchor-post=22 style=3D=22position: relative;font-f=
amily: 'S=46 Pro Display',-apple-system-headline,system-ui,-apple-system,=
BlinkMacSystem=46ont,'Segoe UI',Roboto,Helvetica,Arial,sans-serif,'Apple =
Color Emoji','Segoe UI Emoji','Segoe UI Symbol';font-weight: bold;-webkit=
-font-smoothing: antialiased;-moz-osx-font-smoothing: antialiased;-webkit=
-appearance: optimizelegibility;-moz-appearance: optimizelegibility;appea=
rance: optimizelegibility;margin: 1em 0 0.625em 0;color: rgb(54,55,55);li=
ne-height: 1.16em;font-size: 1.625em;=22>The Simple Version</h2>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><strong>Maximum benefit:</strong> <span>Administer MOT=
S-c fasted in the morning, do light cardio, eat a solid meal a few hours =
later, then train.</span></p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><strong>Constrained schedule:</strong> <span>Administe=
r MOTS-c and train in the morning anyway. Still worth it.</span></p>
<div style=3D=22font-size: 16px;line-height: 26px;=22>
<hr style=3D=22margin: 32px 0;padding: 0;height: 1px;background: rgb(0,0,=
0,.1);border: none;=22 /></div>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><em>=46or research use only, not for human consumption=
. This is not medical advice or personal advice =E2=80=94 strictly educat=
ional.</em></p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22>I want to give a huge shoutout to Coach Cam because he=
 provided a lot of different perspectives on this through his research as=
 well.</p>
<p style=3D=22margin: 0 0 20px 0;color: rgb(54,55,55);line-height: 26px;f=
ont-size: 16px;=22><em>Questions or thoughts=3F Drop them in the comments=
.</em></p>
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