Delivered-To: tjphuhs@gmail.com Received: by 2002:a5d:649e:0:b0:439:fcfb:30e with SMTP id o30csp670974wri; Sun, 5 Apr 2026 10:05:43 -0700 (PDT) X-Received: by 2002:a05:620a:2a04:b0:8cd:b617:6522 with SMTP id af79cd13be357-8d41c6aa4ecmr1358362985a.29.1775408742839; Sun, 05 Apr 2026 10:05:42 -0700 (PDT) ARC-Seal: i=1; a=rsa-sha256; t=1775408742; cv=none; d=google.com; s=arc-20240605; b=Z9nX+Vrh15x7ws7sODMrgpLJMbdzsx66nSCoAa0v+6DpnvDWf2z+ru3m6C3gdqg455 DTNg2fEpKGQKF06s3djOucIMlFVNuYNvzKKP4OeR4n2R8+348Li/PuOtlKMvSpvGmuCV z8TfMcrJ5DptFpWvtYVQXVV9OMbZKsgPKg2xaIGdAlPwJELOYl0PThlQxmd40MJhy22D zLCLfn/QnCJVMARVWUJzsBHTrpWuKqk41n2PlzG+RsBR0ITt1OJ0hSAmUgKU+uDHW2UM PHBvJeAb/CJL3dr6WWDd9dxsdBmktuZHB3SqBTBmAnVwqyR8sALQ4tqUT+ju+1dH71I+ 9CMQ== ARC-Message-Signature: i=1; a=rsa-sha256; c=relaxed/relaxed; d=google.com; s=arc-20240605; h=list-unsubscribe-post:list-unsubscribe:list-post:list-id :list-archive:list-url:list-owner:reply-to:in-reply-to:references :sender:feedback-id:date:message-id:to:from:subject:mime-version :dkim-signature:dkim-signature; bh=eyTkdmS+lzAx46xlxDL8iJHd2x7OLypvdVQT1+odZ6I=; fh=9zP21OW67FFZD2VV42mGudo540Qp4aalMWxJB5kMYug=; b=hziXtDZ8o/GFFL7hfPBjZvrliCG6hRZKrCmuDu9vU9cbOEpzUmfhef2bdB/V+eOyCc Q9W7vrMiKLLiUDRyh78+WWMsnaN0QnKG1AZH6G2o/XLAllchCG7T2BXieDO2l7WQGA2M EPuseklr6OFJTv8IyVl4Rz7nkAD4pYUKW2LH0bipjf3sTwOgUyoeWzHLLS2PkVgVqXzi xAc5bPMFwCrXFPWr1qpPJuouCydVg2I7zI61CHuCyiVxcNGfTDrQKK56mwixzK+uQnLc MkB+K/eUjcGOHW+GE91uz+55pxxA+Eo3CEsWd/dzJr4TeHBCaOr6rnWJ+9b+3916XNat TOpg==; dara=google.com ARC-Authentication-Results: i=1; mx.google.com; dkim=pass header.i=@mg-d1.substack.com header.s=k1 header.b=V4RgYo7F; dkim=pass header.i=@mailgun.org header.s=mg header.b=aIzvFLzd; spf=pass (google.com: domain of bounce+30b528.39b08c6-tjphuhs=gmail.com@mg-d1.substack.com designates 159.112.244.3 as permitted sender) smtp.mailfrom="bounce+30b528.39b08c6-tjphuhs=gmail.com@mg-d1.substack.com"; dmarc=pass (p=REJECT sp=REJECT dis=NONE) header.from=substack.com Return-Path: Received: from v53.v5375b7fa.use4.send.mailgun.net (v53.v5375b7fa.use4.send.mailgun.net. [159.112.244.3]) by mx.google.com with UTF8SMTPS id af79cd13be357-8d2a4eb51f8si1228254485a.144.2026.04.05.10.05.42 for (version=TLS1_2 cipher=ECDHE-ECDSA-AES128-GCM-SHA256 bits=128/128); Sun, 05 Apr 2026 10:05:42 -0700 (PDT) Received-SPF: pass (google.com: domain of bounce+30b528.39b08c6-tjphuhs=gmail.com@mg-d1.substack.com designates 159.112.244.3 as permitted sender) client-ip=159.112.244.3; Authentication-Results: mx.google.com; dkim=pass header.i=@mg-d1.substack.com header.s=k1 header.b=V4RgYo7F; dkim=pass header.i=@mailgun.org header.s=mg header.b=aIzvFLzd; spf=pass (google.com: domain of bounce+30b528.39b08c6-tjphuhs=gmail.com@mg-d1.substack.com designates 159.112.244.3 as permitted sender) smtp.mailfrom="bounce+30b528.39b08c6-tjphuhs=gmail.com@mg-d1.substack.com"; dmarc=pass (p=REJECT sp=REJECT dis=NONE) header.from=substack.com DKIM-Signature: a=rsa-sha256; v=1; c=relaxed/relaxed; d=mg-d1.substack.com; q=dns/txt; s=k1; t=1775408742; x=1775415942; h=List-Unsubscribe-Post: List-Unsubscribe: List-Post: List-Id: List-Archive: List-Owner: Reply-To: In-Reply-To: References: Sender: Sender: Date: Message-Id: To: To: From: From: Subject: Subject: Content-Type: Mime-Version: X-Feedback-Id; bh=eyTkdmS+lzAx46xlxDL8iJHd2x7OLypvdVQT1+odZ6I=; b=V4RgYo7F9qV/W5fSkAwkOqRRLOSQV20iIwzdz1hvZ2qx10Y1VlKmKA5abIL/4sa4NebfTMdvSHpqfJr3CzPMa7Fx+ujmctFC09vYFsieyQwX0GJe81/PwWGyCFGgZv1sTgX2CKM98JvnAdqu7/QH1jHxQjDuxzp+gL8n+DmRd0o= DKIM-Signature: a=rsa-sha256; v=1; c=relaxed/relaxed; d=mailgun.org; q=dns/txt; s=mg; t=1775408742; x=1775415942; h=List-Unsubscribe-Post: List-Unsubscribe: List-Post: List-Id: List-Archive: List-Owner: Reply-To: In-Reply-To: References: Sender: Sender: Date: Message-Id: To: To: From: From: Subject: Subject: Content-Type: Mime-Version: X-Feedback-Id; bh=eyTkdmS+lzAx46xlxDL8iJHd2x7OLypvdVQT1+odZ6I=; b=aIzvFLzdKx4YcJdZk+YhPCsZoun/ky7EFL4C1ABNr+Fq/GprBxHxeZxz/ZeFpycdgspCd4PghkOrc4sAmDiJ0/L4SwRYj7fJllkz/PCz02IW/ZluOdPEGMO8g9P77CjAFb/3qZxhJSGHqb429wqh75t5DI7PTVVcHpMKe7Tj+aE= X-Mailgun-Sid: WyIxMWU0ZSIsInRqcGh1aHNAZ21haWwuY29tIiwiMzliMDhjNiJd X-Feedback-Id: postmaster@mg-d1.substack.com:post:614a1297c57bbbe25fa40e08:mailgun Received: by 24fe46eb3c968da621db8bf9f73777188b0bfdb2e7dee603a9dc60a6d662bc1c with HTTP id 69d29666f2f7fa4308430002; Sun, 05 Apr 2026 17:05:42 GMT X-Mailgun-Sending-Ip: 159.112.244.3 Mime-Version: 1.0 Content-Type: multipart/alternative; boundary="5eef767f7e0c864d8ed1cd6166c278d58f5b84627501d1ce5c73c1be8c3c" Subject: Does SS-31 Still Make Sense If MOTS-C Improves Mitochondria? From: Derek from Peptide Price To: tjphuhs@gmail.com X-Mailgun-Tag: post X-Mailgun-Track-Clicks: false Message-Id: <20260405170535.3.4c1c0ee9704a5a86@mg-d1.substack.com> Date: Sun, 5 Apr 2026 17:05:35 +0000 Feedback-Id: post-193269178:cat-post:pub-3365367:substack Sender: Derek from Peptide Price References: In-Reply-To: Reply-To: Derek from Peptide Price List-Owner: List-Url: List-Archive: List-Id: List-Post: List-Unsubscribe: List-Unsubscribe-Post: List-Unsubscribe=One-Click X-Mailgun-Variables: {"category": "post", "email_generated_at": "1775408742425", "is_freemail": "true", "post_audience": "everyone", "post_id": "193269178", "post_type": "newsletter", "pub_community_enabled": "true", "publication_id": "3365367", "subdomain": "derekpruski", "user_id": "273622398"} --5eef767f7e0c864d8ed1cd6166c278d58f5b84627501d1ce5c73c1be8c3c Content-Type: text/plain; charset="utf-8" Content-Transfer-Encoding: quoted-printable View this post on the web at https://derekpruski.substack.com/p/does-ss-31-= still-make-sense-if-mots This is a follow-up to my three-part breakdown of the January 9th MOTS-c st= udy out of the University of Copenhagen. A great question came up in the co= mments after Part 1 =E2=80=94 if both MOTS-c and SS-31 improve existing mit= ochondria rather than building new ones, what=E2=80=99s the point of resear= ching both? It=E2=80=99s a fair question, and the answer actually makes the= case for SS-31 stronger, not weaker. Want to read the full study? https://= pubmed.ncbi.nlm.nih.gov/41520850/ [ https://substack.com/redirect/06992678-= 21c5-4b57-873c-e90bba839eb2?j=3DeyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRX= GMy3p768BWtuZifRB-Zs ] For research purposes only. Not for human consumption. Quick Recap =E2=80=94 What Did the MOTS-c Study Tell Us? The study confirmed that MOTS-c improves mitochondrial performance without = increasing the number of mitochondria. It does this by activating two signa= ling pathways =E2=80=94 AMPK and PGC-1=CE=B1 =E2=80=94 which turn up genes = related to energy production efficiency, structural integrity, and oxidativ= e stress management. It=E2=80=99s a top-down signal. The mitochondria recei= ve an instruction to operate better, and they do. So What Does SS-31 Do? SS-31 (also called Elamipretide) works at a completely different layer of m= itochondrial function. To understand it, you need to know about one specifi= c structure inside your mitochondria. Inside every mitochondrion there=E2=80=99s an inner membrane =E2=80=94 thin= k of it as the production floor where energy actually gets made. Embedded i= n that membrane is a series of proteins called the electron transport chain= , which is the assembly line that converts fuel into ATP (usable energy). F= or that assembly line to work properly, it needs to stay organized and inta= ct. That organization depends heavily on a lipid called cardiolipin. Cardiolipi= n is found almost exclusively on the inner mitochondrial membrane, and its = job is to hold the electron transport chain together and keep it functionin= g efficiently. Here=E2=80=99s the problem. With age, oxidative stress, and cellular damage= , cardiolipin gets damaged and disorganized. When that happens: The electron transport chain starts to fall apart Energy production becomes inefficient Electrons start leaking out of the assembly line Those leaked electrons become ROS =E2=80=94 the cellular waste that damages= proteins, DNA, and the mitochondria themselves over time SS-31 binds directly to cardiolipin and stabilizes it. It=E2=80=99s a physi= cal repair and protection mechanism at the membrane level. The Key Difference Between the Two This is the part that answers the original question. Both MOTS-c and SS-31 improve existing mitochondria and reduce ROS. On the = surface that looks redundant. But the way they do it couldn=E2=80=99t be mo= re different: MOTS-c works like software =E2=80=94 it sends a signal through AMPK and PGC= -1=CE=B1 that reprograms how mitochondria operate at the gene expression le= vel. It=E2=80=99s a top-down instruction. SS-31 works like hardware repair =E2=80=94 it goes directly to the inner me= mbrane, stabilizes the physical structure, and prevents the assembly line f= rom falling apart at the source. It=E2=80=99s a bottom-up structural fix. One is optimizing the system through signaling. The other is repairing and = protecting the physical components the system runs on. They=E2=80=99re work= ing on the same machine from completely opposite directions. The ROS Reduction =E2=80=94 Why Both Still Matter Both compounds reduce ROS, which at first glance also seems redundant. But = again the mechanism is different: SS-31 reduces ROS by physically stabilizing the membrane so fewer electrons= escape during energy production =E2=80=94 it=E2=80=99s preventing the leak= at the source MOTS-c reduces ROS by upregulating the genes that manage the cell=E2=80=99s= internal oxidative stress response =E2=80=94 it=E2=80=99s improving the cl= eanup system One is stopping the problem from happening. The other is improving the body= =E2=80=99s ability to deal with it when it does. Addressing oxidative stres= s from two different angles simultaneously is more comprehensive than eithe= r approach alone. The Simple Analogy Think of a car engine running poorly. SS-31 is like replacing worn gaskets and stabilizing the internal component= s so the engine doesn=E2=80=99t leak and lose pressure MOTS-c is like reprogramming the engine=E2=80=99s computer to optimize fuel= delivery, timing, and efficiency Both improve performance. But one is working at the hardware level and the = other at the software level. You wouldn=E2=80=99t say one makes the other p= ointless =E2=80=94 if anything, fixing both layers together gets you furthe= r than either one alone. The Bottom Line The MOTS-c study actually reinforces why SS-31 is worth researching, not th= e opposite. MOTS-c having a well-defined signaling mechanism makes it clear= er that SS-31 is filling a different role entirely =E2=80=94 structural sta= bilization at the membrane level that MOTS-c doesn=E2=80=99t address. They= =E2=80=99re not competing compounds. They=E2=80=99re targeting different la= yers of the same problem, which is exactly why they=E2=80=99re frequently d= iscussed together in mitochondrial health research. As always =E2=80=94 for research purposes only, not for human consumption. =E2=80=94 Derek Unsubscribe https://substack.com/redirect/2/eyJlIjoiaHR0cHM6Ly9kZXJla3BydXN= raS5zdWJzdGFjay5jb20vYWN0aW9uL2Rpc2FibGVfZW1haWw_dG9rZW49ZXlKMWMyVnlYMmxrSW= pveU56TTJNakl6T1Rnc0luQnZjM1JmYVdRaU9qRTVNekkyT1RFM09Dd2lhV0YwSWpveE56YzFOR= EE0TnpReUxDSmxlSEFpT2pFNE1EWTVORFEzTkRJc0ltbHpjeUk2SW5CMVlpMHpNelkxTXpZM0lp= d2ljM1ZpSWpvaVpHbHpZV0pzWlY5bGJXRnBiQ0o5LldUdTJVc1dSRE96OUpUaFlTdlViM0ROWTh= RWWlyNF9rcUc4dzliQ3lmR1UiLCJwIjoxOTMyNjkxNzgsInMiOjMzNjUzNjcsImYiOnRydWUsIn= UiOjI3MzYyMjM5OCwiaWF0IjoxNzc1NDA4NzQyLCJleHAiOjIwOTA5ODQ3NDIsImlzcyI6InB1Y= i0wIiwic3ViIjoibGluay1yZWRpcmVjdCJ9.Mut_dvw5miVIx_qHjSz_gbx1CfIXYY46agYjpZA= tfE0? --5eef767f7e0c864d8ed1cd6166c278d58f5b84627501d1ce5c73c1be8c3c Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable = Does SS-31 Still Make Sense If MOTS-C Improves Mitochondria?3D""
This is a follow-up to my three-part breakdown of the January 9th M= OTS-c study out of the University of Copenhagen.
͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­͏     ­͏     = ­͏     ­͏     ­͏  =   ­͏     ­͏     ­T= 7;     ­͏     ­͏     &= #173;͏     ­͏     ­͏   =   ­͏     ­͏     ­͏= ;     ­͏     ­͏     &#= 173;͏     ­͏     ­͏   &= #8199; ­͏     ­͏     ­͏=     ­͏     ­͏     = 73;͏     ­͏     ­͏   &#= 8199; ­͏     ­͏     ­͏ =     ­͏     ­͏     = 3;͏     ­͏     ­͏   = 199; ­͏     ­͏     ­͏ &= nbsp;   ­͏     ­͏     ­= ;͏     ­͏     ­͏   Q= 99; ­͏     ­͏     ­͏ &n= bsp;   ­͏     ­͏     ­= ͏     ­͏     ­͏   ̳= 9; ­͏     ­͏     ­͏ &nb= sp;   ­͏     ­͏     ­&= #847;     ­͏     ­͏    = ; ­͏     ­͏     ­͏ &nbs= p;   ­͏     ­͏     ­&#= 847;     ­͏     ­͏    = ­͏     ­͏     ­͏  = ;   ­͏     ­͏     ­= 47;     ­
Forwarded t= his email? Subscribe here f= or more
<= td>
 
=3D""
= 3D""
3D""
 

This is a follow-up to my three-part breakdow= n of the January 9th MOTS-c study out of the University of Copenhagen. A gr= eat question came up in the comments after Part 1 — if both MOTS-c an= d SS-31 improve existing mitochondria rather than building new ones, what&#= 8217;s the point of researching both? It’s a fair question, and the a= nswer actually makes the case for SS-31 stronger, not weaker. Want to read = the full study? For researc= h purposes only. Not for human consumption.

Upgrade to paid

Quick Recap — What Did the MOTS-c Stu= dy Tell Us?

The study confirmed that MOTS-c improv= es mitochondrial performance without increasing the number of mitochondria.= It does this by activating two signaling pathways — AMPK and PGC-1&#= 945; — which turn up genes related to energy production efficiency, s= tructural integrity, and oxidative stress management. It’s a top-down= signal. The mitochondria receive an instruction to operate better, and the= y do.

So What Does SS-31 Do?

SS-31 (also called Elamipretide) works at a completely different layer of = mitochondrial function. To understand it, you need to know about one specif= ic structure inside your mitochondria.

Inside every mitocho= ndrion there’s an inner membrane — think of it as the productio= n floor where energy actually gets made. Embedded in that membrane is a ser= ies of proteins called the electron transport chain, which is the assembly = line that converts fuel into ATP (usable energy). For that assembly line to= work properly, it needs to stay organized and intact.

That organization depends heavily on a lipid called cardio= lipin. Cardiolipin is found almost exclusively on the inner = mitochondrial membrane, and its job is to hold the electron transport chain= together and keep it functioning efficiently.

Here&= #8217;s the problem. With age, oxidative stress, and cellular damage, cardi= olipin gets damaged and disorganized. When that happens:

SS-31 binds directly to cardiolipin and stabilize= s it. It’s a physical repair and protection mechanism = at the membrane level.

The Key Difference Betw= een the Two

This is the part that answers the orig= inal question.

Both MOTS-c and SS-31 improve existing mitoc= hondria and reduce ROS. On the surface that looks redundant. But the way th= ey do it couldn’t be more different:

=

One is optimizing the system through signaling. The other is r= epairing and protecting the physical components the system runs on. They= 217;re working on the same machine from completely opposite directions.

=
The ROS Reduction — Why Both Still Matter=

Both compounds reduce ROS, which at first glance also seem= s redundant. But again the mechanism is different:

  • SS-31 reduces ROS by physically stabilizing the membrane s= o fewer electrons escape during energy production — it’s preven= ting the leak at the source

  • MOTS-c reduces ROS by upregulating= the genes that manage the cell’s internal oxidative stress response = — it’s improving the cleanup system

One is stopping the problem from happening. The other is improving th= e body’s ability to deal with it when it does. Addressing oxidative s= tress from two different angles simultaneously is more comprehensive than e= ither approach alone.

=

The Simple Analogy

=

Think of a car engine running poorly.

  • SS-31 is like replacing worn gaskets and stabilizing the i= nternal components so the engine doesn’t leak and lose pressure

  • MOTS-c<= /strong> is like reprogramming the engine’s computer to optimiz= e fuel delivery, timing, and efficiency

Bo= th improve performance. But one is working at the hardware level and the ot= her at the software level. You wouldn’t say one makes the other point= less — if anything, fixing both layers together gets you further than= either one alone.

The Bottom Line

The MOTS-c study actually reinforces why SS-31 is worth researching,= not the opposite. MOTS-c having a well-defined signaling mechanism makes i= t clearer that SS-31 is filling a different role entirely — structura= l stabilization at the membrane level that MOTS-c doesn’t address. Th= ey’re not competing compounds. They’re targeting different laye= rs of the same problem, which is exactly why they’re frequently discu= ssed together in mitochondrial health research.

As always &= #8212; for research purposes only, not for human consumption.

— Derek

Upgrade= to paid

Yo= u're currently a free subscriber to Peptide Price. For the full experience, upgrad= e your subscription.

Upgrade to= paid

3D""
 
=
3D""Share
 
&nbs= p;
3D""Like
3D"=Comme= nt
3D""Restack
 

= 9; 2026 Derek Pruski
548 Market Street PMB 72296, San Franc= isco, CA 94104
Unsubscri= be

3D"Start

3D"" --5eef767f7e0c864d8ed1cd6166c278d58f5b84627501d1ce5c73c1be8c3c--