Latest / The Peptide Research Podcast / Episode 86 SS-31 as hardware, MOTS-C as software, NAD+ as fuel [Mitochondrial Trio]

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Episode 86 SS-31 as hardware, MOTS-C as software, NAD+ as fuel [Mitochondrial Trio] · The Peptide Research Podcast

• 0:45
  SPEAKER_02: Todd, a question most people get backwards.
• 0:47
  SPEAKER_02: If a cell is running low on energy, is that a fuel problem?
• 0:51
  SPEAKER_00: Almost never only a fuel problem.
• 0:53
  SPEAKER_02: Okay, that's not the answer I had queued up.
• 0:55
  SPEAKER_00: Nobody does.
• 0:56
  SPEAKER_00: When your car won't move, you think about the tank, but a cell has three separate things that all have to be working.
• 1:02
  SPEAKER_00: The structure doing the converting, the instructions telling it how hard to run, and the fuel itself.
• 1:08
  SPEAKER_00: And three compounds keep getting studied together because each asks about a different layer.
• 1:13
  SPEAKER_02: So it's not three versions of one idea.
• 1:16
  SPEAKER_00: Three different questions that happen to share a room.
• 1:18
  SPEAKER_02: Then let's take them one at a time.
• 1:20
  SPEAKER_02: I'm Amy Andrews, and this is the PeptideResearch.us podcast.
• 1:24
  SPEAKER_02: Today it's SS Spirity1, MOTS C, and NAD Plus hardware, software, and fuel.
• 1:31
  SPEAKER_02: Todd Collins is with me.
• 1:32
  SPEAKER_02: Todd, what does somebody walk away with?
• 1:35
  SPEAKER_00: You'll know why a fat molecule ends up being structural, why a peptide written in mitochondrial DNA travels upstairs to the nucleus, what a cofactor actually does, and why none of the three stands in for another.
• 1:47
  SPEAKER_00: One note before we get going.
• 1:49
  SPEAKER_00: All peptides discussed in this podcast relate to research use only.
• 1:53
  SPEAKER_00: Any references to data from animals, cells, or human studies relate exclusively to scientific literature and not to products from NRG biolabs.
• 2:02
  SPEAKER_00: These compounds are not approved drugs or dietary supplements and are not for human consumption.
• 2:08
  SPEAKER_00: Nothing in this podcast is medical advice.
• 2:10
  SPEAKER_02: Hardware first, what's the actual machine?
• 2:13
  SPEAKER_00: Inside every mitochondrion, there's an inner membrane, and it isn't smooth, it's folded over and over into pleats called cristae.
• 2:20
  SPEAKER_00: Those folds are where the electron transport chain sits, the row of protein complexes that hand electrons down a line and build ATP at the end.
• 2:29
  SPEAKER_00: ATP being the currency every process in your body spends.
• 2:33
  SPEAKER_02: Why fold it at all?
• 2:34
  SPEAKER_00: Surface area.
• 2:35
  SPEAKER_00: More pleats means more room for the assembly line, so the shape isn't decoration, the shape is capacity.
• 2:41
  SPEAKER_00: And what holds a pleat and a pleat?
• 2:43
  SPEAKER_00: Cardiolipin.
• 2:44
  SPEAKER_00: It's a fat molecule and an odd one.
• 2:46
  SPEAKER_00: It carries four tails instead of the usual two, which gives it a cone shape that lets a membrane curve.
• 2:52
  SPEAKER_00: It lives almost exclusively in that inner membrane, and the transport complexes don't merely sit near it, they're organized by it.
• 3:00
  SPEAKER_02: So this is a construction site.
• 3:02
  SPEAKER_02: Cardiolipin isn't a worker, it's the scaffolding.
• 3:05
  SPEAKER_02: Every trade can be on site with all their tools.
• 3:07
  SPEAKER_02: If the scaffolding sags, nobody reaches the wall they're meant to be working on.
• 3:11
  SPEAKER_00: That's exactly the geometry problem.
• 3:13
  SPEAKER_02: So where does SS-31 come in?
• 3:16
  SPEAKER_00: SS-31 is a small peptide studied for one specific property.
• 3:20
  SPEAKER_00: It concentrates in that inner membrane and associates with cardiolipin.
• 3:24
  SPEAKER_00: The research interest is membrane organization, whether the pleats stay tidy and the transport chain stays lined up.
• 3:31
  SPEAKER_02: Give me the lab view.
• 3:32
  SPEAKER_00: When cardiolipin is damaged and it's exposed because it sits right where reactive oxygen species get produced, researchers observe the cristae losing that tight structure, complexes drift apart, handoffs get sloppier, and more electrons leak out early.
• 3:46
  SPEAKER_00: Where the organization holds, the handoffs stay clean.
• 3:49
  SPEAKER_02: So what they're watching isn't a fuel gauge, it's whether the line is still straight.
• 3:54
  SPEAKER_02: Level two, why does one leaked electron matter?
• 3:57
  SPEAKER_00: Because a leaked electron becomes a reactive oxygen species, and those damage cardiolipin.
• 4:03
  SPEAKER_00: A sloppy line makes the line sloppier.
• 4:05
  SPEAKER_02: Wait, so that's a feedback loop.
• 4:08
  SPEAKER_02: That's not decline, that's a spiral.
• 4:10
  SPEAKER_00: Researchers describe it in almost those words, which is why structure gets studied on its own terms, rather than lumped in with supply.
• 4:17
  SPEAKER_02: Software next.
• 4:18
  SPEAKER_02: MOTS C.
• 4:19
  SPEAKER_00: Right.
• 4:20
  SPEAKER_00: Your mitochondria carry their own small circular genome separate from the DNA in the nucleus, a leftover from a bacterial ancestor.
• 4:28
  SPEAKER_00: MOTS C is a peptide encoded in that genome.
• 4:31
  SPEAKER_02: And it does what?
• 4:32
  SPEAKER_00: Under metabolic stress, it moves into the nucleus and influences which genes get expressed there.
• 4:37
  SPEAKER_00: The best described route runs through AMPK, AMPK activated protein kinase, the cell's low-fuel sensor.
• 4:45
  SPEAKER_00: When available energy drops, AMPK activates and shifts priorities towards producing energy and away from expensive building projects.
• 4:54
  SPEAKER_02: Okay, that's air traffic control.
• 4:56
  SPEAKER_02: The runway hasn't changed and the planes haven't changed, but somebody in the tower is deciding what lands first when the weather turns.
• 5:02
  SPEAKER_00: And when the tower goes quiet, the planes don't disappear.
• 5:05
  SPEAKER_00: They just stack up badly.
• 5:07
  SPEAKER_02: What does that look like in a lab?
• 5:08
  SPEAKER_00: Suppress MOT C signaling in cells, and you see a blunted response to a metabolic challenge.
• 5:13
  SPEAKER_00: The shift towards energy production that should follow is muted.
• 5:17
  SPEAKER_00: Leave the signaling intact, and that adaptation shows up clearly.
• 5:21
  SPEAKER_00: So nobody's measuring how much energy is present.
• 5:24
  SPEAKER_00: They're measuring reaction time.
• 5:25
  SPEAKER_02: And reaction time isn't something more fuel buys you.
• 5:29
  SPEAKER_00: Which brings us neatly to fuel.
• 5:30
  SPEAKER_00: NAD plus.
• 5:31
  SPEAKER_00: NAD plus is nicotinamide adenine dinucleotide, and it's a cofactor, a helper molecule certain enzymes can't function without.
• 5:40
  SPEAKER_00: It isn't fuel exactly.
• 5:41
  SPEAKER_00: It's the shuttle.
• 5:42
  SPEAKER_00: It picks up electrons from the breakdown of food and hands them to that transport chain.
• 5:47
  SPEAKER_01: So it's carrying the cargo.
• 5:49
  SPEAKER_01: It isn't the cargo.
• 5:50
  SPEAKER_00: And it flips between two forms, doing it, over and over, which means the interesting variable isn't the total amount sitting around, it's how briskly it's cycling.
• 5:59
  SPEAKER_01: I always hear Sirtuans in the same breath.
• 6:01
  SPEAKER_00: Because certuins spend it.
• 6:03
  SPEAKER_00: They're a family of enzymes tied to DNA repair and to how cells manage stress, and they consume NAD plus doing that work.
• 6:10
  SPEAKER_00: So one pool serves two demands.
• 6:13
  SPEAKER_00: The energy line and the repair crew both draw on it.
• 6:16
  SPEAKER_02: That's a bank account with two people spending from it.
• 6:19
  SPEAKER_02: Everything is fine right up until the month a big repair bill and payroll land on the same day.
• 6:24
  SPEAKER_00: And neither party knew the other was withdrawing.
• 6:26
  SPEAKER_00: It's also why NAD Plus turns up in the aging conversation.
• 6:30
  SPEAKER_00: Levels are described as declining over time.
• 6:33
  SPEAKER_02: Let me pause on why sourcing matters this much.
• 6:35
  SPEAKER_02: Everything here is a subtle signal read against a noisy background.
• 6:39
  SPEAKER_02: A contaminant can look exactly like an effect.
• 6:42
  SPEAKER_02: That's the role NLG Biolabs plays as the foundational partner behind the show.
• 6:47
  SPEAKER_02: Certificates of analysis, third-party testing, batch documentation.
• 6:51
  SPEAKER_02: You can see the COAs and view the lab standards at peptideresearch.us.
• 6:55
  SPEAKER_00: Clean answers need clean inputs.
• 6:57
  SPEAKER_02: So why do these three end up on the same page?
• 6:59
  SPEAKER_00: Because each answers something the others can't.
• 7:02
  SPEAKER_00: Fuel doesn't straighten a bent assembly line, a tidy line doesn't tell a cell to adapt, and a perfect instruction doesn't help if there's nothing carrying electrons.
• 7:11
  SPEAKER_00: Researchers set them side by side to keep the layers separate, not to blur them.
• 7:16
  SPEAKER_02: Oh, so the point of the trio isn't that it's bigger, it's a way of asking three questions without confusing them.
• 7:22
  SPEAKER_00: That's why the framing stuck.
• 7:24
  SPEAKER_00: And can I tell you when it got concrete for me?
• 7:26
  SPEAKER_00: Years back, I watched a group chase a disappointing energy result for months by adding more substrate, more raw material in.
• 7:34
  SPEAKER_00: Nothing moved.
• 7:35
  SPEAKER_00: Somebody finally imaged the membranes, and the Christae were a mess.
• 7:39
  SPEAKER_02: Oh, that's painful.
• 7:40
  SPEAKER_00: We'd been topping off the tank on a car with a bent driveshaft.
• 7:43
  SPEAKER_00: Ever since I ask which layer I'm looking at before I ask how much of anything there is.
• 7:48
  SPEAKER_02: Mine's the kitchen version.
• 7:50
  SPEAKER_02: I spent an entire autumn convinced the answer was more coffee, drowning in caffeine by two and still foggy at four.
• 7:57
  SPEAKER_00: More fuel into a system that wasn't asking about fuel.
• 8:00
  SPEAKER_02: I was sleeping five hours a night and calling it a personality.
• 8:03
  SPEAKER_02: Let me recap.
• 8:04
  SPEAKER_02: Mitochondria fold their inner membrane into pleats called cristae, and cardiolipin is the unusual fat that lets those folds hold their shape.
• 8:12
  SPEAKER_02: SS31 gets studied for how it associates with cardiolipin and what that means for keeping the transport chain organized.
• 8:19
  SPEAKER_02: MOTS C is written in mitochondrial DNA and travels into the nucleus under stress.
• 8:25
  SPEAKER_02: It works largely through AMPK, the low-fuel sensor, and NAD plus is the cofactor shuttling electrons while sertuans spend it on repair.
• 8:34
  SPEAKER_02: Structure, instruction, currency.
• 8:37
  SPEAKER_00: Clean summary.
• 8:38
  SPEAKER_00: Oh, and one last thing that's easy to overlook.
• 8:40
  SPEAKER_00: Two of the three don't do any work at all.
• 8:43
  SPEAKER_00: Cardiolipin is a fat.
• 8:45
  SPEAKER_00: NAD plus is a helper molecule.
• 8:47
  SPEAKER_00: Neither one converts anything.
• 8:49
  SPEAKER_00: They make converting possible.
• 8:51
  SPEAKER_00: That's the pattern across this whole field.
• 8:53
  SPEAKER_00: The molecule worth studying is rarely the one holding the tools.
• 8:56
  SPEAKER_02: If that opened a door, there's a plain language write-up on all three waiting at peptidesearch.us.
• 9:02
  SPEAKER_02: The energy and anti aging section is where I'd start.
• 9:05
  SPEAKER_02: If you like this podcast and want to stay up to date on all the latest peptide research, you can find links to our website, Facebook page, and even our Discord channel in the podcast description below.
• 9:14
  SPEAKER_02: You can even sign up for our newsletter and get notified every time a new episode rolls out.
• 9:18
  SPEAKER_02: And that's our show.
• 9:19
  SPEAKER_02: Go get curious about your own wirings.