What Polynucleotides Actually Do to Your Skin
Updated: Aug 20
Someone sits down and says their face hasn't really changed, but their skin looks different. No obvious volume loss, no real sagging. Just duller, finer, less resilient, sometimes crepey where it wasn't before. And the things that used to visibly help don't seem to do quite as much anymore.
That distinction matters more than most people assume, because skin ageing isn't just a story about losing collagen. It's also a story about what's happening to the cells responsible for making it in the first place. That's the territory polynucleotides sit in, and it's worth understanding properly before you decide whether they're relevant to you.
"Regenerative" tells you nothing
I'll say something that probably isn't good for business. Almost everything in aesthetics gets called regenerative now, and the word has stopped meaning anything specific. It describes a hope, not a mechanism. It tells you someone expects a tissue to function better afterwards. It doesn't tell you how.
Polynucleotides get lumped in with fillers for the same lazy reason, and it's worth untangling because the confusion leads people toward the wrong treatment. They don't restore a hollow temple. They don't replace lost cheek volume. They don't lift a lax lower face. They're aimed at a different problem entirely, which is skin quality rather than facial volume, and once that distinction is clear the whole conversation gets easier.
What's actually happening in ageing skin
Collagen decline is the answer everyone reaches for, and it's real, but it's only part of the picture.
Your dermis is maintained by fibroblasts, the cells responsible for producing much of the collagen, elastin and surrounding structure that gives skin its resilience. As skin ages, particularly after years of cumulative ultraviolet exposure, fibroblast activity changes. The cells haven't vanished. They've become less productive and less responsive to the signals that used to keep the surrounding tissue in good order, which is a genuinely different problem from a hollow where volume used to be.
That reframes the question. Instead of asking what you could add to replace what's missing, you start asking whether you can influence the cells still responsible for maintaining what's there. That's the biological ground polynucleotides are trying to occupy.
What they are, and what actually happens once they're in
Polynucleotides are purified DNA-derived polymers. Some aesthetic products use salmonid-derived material, which is where the "salmon DNA" description comes from, though the origin story matters far less than what happens to the molecule once it's in tissue.
Unlike a conventional filler, whose job is to occupy space and provide structural support, polynucleotides are proposed to work through biological signalling. Once administered, the long DNA chains break down progressively into smaller fragments, and those fragments have been studied for their interaction with cellular pathways including the adenosine A2A receptor. In laboratory and preclinical research, that's been associated with increased fibroblast activity, extracellular matrix production, and some modulation of inflammatory signalling, alongside a proposed salvage pathway supporting cellular repair.
Here's where I want to be honest rather than impressive. This isn't hydration in a syringe. The theory is that you're changing the environment the skin's own cells operate in, and that's a genuinely more interesting proposition than most injectables offer. But most of that mechanistic literature is laboratory, cellular or preclinical work. It explains how something might work. It doesn't prove the size of effect a patient will actually notice, and those are two different questions I try never to blur together in a consultation.
Two things I won't let a skin-quality conversation ignore
Sun exposure is the first. Ultraviolet radiation accelerates the breakdown of dermal collagen and drives most of what we call photoageing, which is why two people with identical birthdays can have remarkably different skin. Their cumulative exposure was never identical, even if their years were. If UV is continually degrading collagen, treating skin quality while ignoring the exposure causing the damage is a fairly inefficient way to spend money. Daily broad-spectrum SPF remains one of the highest-return things anyone can do for how their skin looks in a decade, and it's never going to sound glamorous enough to compete with a syringe.
Glycation is the second, and it's the one I find genuinely fascinating, because it sits exactly on the border between aesthetics and the longevity work I've trained in more recently. When sugars react with long-lived proteins like collagen, they form advanced glycation end products, glucosepane being one of the better-studied examples, and over time those cross-links stiffen the tissue and change its physical properties. Collagen quantity was never the whole story. The condition of the collagen already there matters just as much, and that's a real limitation for any treatment built purely around stimulating more of it. Stimulating fibroblasts to lay down new collagen doesn't undo cross-linking that's already formed, and I'd rather say that plainly than let a patient assume otherwise.
What polynucleotides can't do
They're not a substitute for lost volume. A hollow temple stays hollow no matter how much you influence fibroblast activity. They're not a facelift, and improving skin quality is not the same thing as repositioning tissue that has genuinely descended. And they don't reverse every molecular consequence of ageing. Established collagen cross-linking isn't undone simply because you've stimulated the cells around it.
That matters because the best treatment is never the one with the most impressive description. It's the one whose mechanism actually matches the problem in front of you.
"My skin has aged" isn't one sentence, clinically
It's the sentence I hear constantly, and it can mean almost anything. Volume loss, skin laxity, dynamic muscle activity, static lines, photodamage, altered texture, reduced elasticity, dehydration, or several of these running together, and none of those share a solution. Sometimes the honest answer, once I've actually looked, is that polynucleotides aren't what you need. That's not the treatment failing. That's the assessment doing its job.
The people I find most interesting to assess usually aren't asking for a dramatic change. They're saying they don't want their face to look different, they just want their skin to feel like it used to. No major volume loss, nothing structurally wrong, just a gradual change in tissue quality. That's exactly where a skin-quality treatment becomes a more logical conversation than reaching for more volume, and it only becomes obvious once someone has actually assessed what's changed rather than what's been requested.
Why I still won't start with the treatment
A photograph shows you plenty. It can't show you skin elasticity, tissue quality, facial movement, volume distribution, sun exposure history or the pattern someone's ageing is actually following. Sometimes the answer is a treatment. Sometimes it's skincare and sun protection. Sometimes it's a different modality altogether, and once in a while the most useful thing I do in an appointment is tell someone the treatment they arrived asking for isn't addressing what's actually bothering them. I'd rather have that conversation before anything gets near a syringe.
What the evidence actually supports
There's good mechanistic reason to take polynucleotides seriously, particularly around fibroblast activity, tissue repair signalling and extracellular matrix biology. There's also a growing clinical literature on their aesthetic and dermatological use. Neither of those is the same as a proven, well-quantified clinical outcome, and conflating a plausible mechanism with a demonstrated result is a mistake I see constantly in this field, where the terminology moves considerably faster than the evidence behind it.
So I don't need polynucleotides to be a miracle. What I actually want to know is whether the mechanism fits the person in front of me, and whether the evidence is strong enough to justify using it on them specifically.
The question worth asking instead
Aesthetics has become very good at asking what treatment you should have. I think the better question is what's actually changed in your skin. If it's volume, that's one conversation. If it's muscle, another. If it's laxity, another again. And if the real issue is that the skin has become less resilient and less able to maintain its own structure, that's when treatments aimed at skin biology genuinely earn their place.
That's where polynucleotides sit for me. Not a miracle, and I'd rather say that once than three times. An attempt to work with the biology of ageing skin rather than simply mask what it's doing.
Frequently asked questions
Are polynucleotides a filler? No. They aren't used to create the volumising or structural effect associated with dermal fillers.
What are they supposed to do? They're being investigated and used for potential effects on skin biology, including fibroblast activity, extracellular matrix production and tissue repair pathways.
How long do they take to work? Not like a filler's immediate volumising effect. Changes in skin quality, where they occur, develop over time as the underlying biological processes take place.
Are they suitable for everyone? No. Whether they're appropriate depends on what's actually driving the change in your skin, your medical history, previous treatments and an individual assessment.
Are they the same as Profhilo? No. They get discussed together because both are marketed around skin quality, but they work through different mechanisms. The useful question isn't which one is better. It's which mechanism actually matches what's happening in your skin.
Where I'd start
If what's changed is skin quality rather than facial shape, the useful starting point isn't a product. It's finding out what's actually driving it.
At Juvenology, that means looking at the skin, tissue quality, facial structure, previous treatments and the wider factors that might be contributing, before any treatment gets recommended. Book a skin assessment to find out whether polynucleotides genuinely make sense for what you're seeing, or whether something else does.
About the author
Marina Kostadinova-Yankova is an NMC-registered nurse and the founder of Juvenology Clinic in Maidstone, Kent.
Before moving into aesthetics, Marina spent six years in cardiac nursing at KIMS Hospital, followed by two years as an Aesthetics Nurse Specialist at Spencer Private Hospitals. She has led her own clinic for eight years.
She has completed the Certified Longevity Physician CME Course at the Geneva College of Longevity Science, and is a HeartMath Certified Practitioner through the HeartMath Institute Interventions Program.
Marina is a member of the British Association of Cosmetic Nurses and the Royal College of Nursing, and is JCCP verified.
Last reviewed August 2026.
References
Comparative review of PDRN and PN, PMC 2025: pmc.ncbi.nlm.nih.gov/articles/PMC12388916
A2A receptor activation, fibroblast differentiation, PMC: pmc.ncbi.nlm.nih.gov/articles/PMC8618295
Systematic review, polynucleotide injections, Journal of Cosmetic Dermatology: onlinelibrary.wiley.com/journal/14732165
PDRN and cellular senescence mitigation, PLOS ONE: journals.plos.org/plosone/article?id=10.1371/journal.pone.0321005
Polynucleotide injections for periorbital rhytides, PMC: pmc.ncbi.nlm.nih.gov/articles/PMC12905022