Stress Ages You. Not as a Metaphor.
At the ends of your chromosomes, repeated sequences of DNA called telomeres are quietly fraying every time your cells divide. Stress accelerates that process.
Could omega-3s slow that damage? To find out, Ohio State assembled a scientific dream team: a Nobel laureate, a pioneering psychoneuroimmunologist, and the world’s leading telomere researchers. Across two NIH-funded trials, the data came back clear: Yes.
But the mechanism behind that result is even more compelling than the answer itself.
The Research Team
Janice K. Kiecolt-Glaser is a Distinguished University Professor at The Ohio State University and directs the Institute for Behavioral Medicine Research. She is one of the most cited researchers in psychoneuroimmunology, a field she helped define — the study of how what happens in our psychological lives shows up in our immune systems. Over decades of research, she has demonstrated that caregiving stress, loneliness, marital conflict, and even the slow grind of daily worry alter wound healing, shift immune function, and raise inflammatory markers. Her work has made the case, paper by paper, that what happens in our lives changes what happens in our cells.
For the 2013 telomere trial, Kiecolt-Glaser brought in Elizabeth Blackburn, Elissa Epel, and Jue Lin from the University of California, San Francisco. Blackburn had won the 2009 Nobel Prize in Physiology or Medicine for co-discovering how telomeres protect chromosomes and how the enzyme telomerase rebuilds them. Epel had collaborated with Blackburn on the landmark research linking chronic psychological stress to shorter telomeres. Lin developed the assays that measure telomere length and telomerase activity in blood samples. Blackburn is a co-author on the 2013 paper.
The 2021 follow-up was led by Annelise Madison, then a researcher in Kiecolt-Glaser’s lab. Kiecolt-Glaser served as senior author. Epel and Lin contributed again from UCSF.
Both trials used one omega-3 formulation: OmegaBrite 7010MD, which has a unique 7:1 EPA-to-DHA ratio. OmegaBrite supplied the supplements and placebos as an unrestricted gift but played no role in study design, data collection, analysis, or publication. Funding came from the NIH.
What Are Telomeres and Telomerase?
Every chromosome in every cell in your body is a long thread of DNA encoding your genes. At the tips of each chromosome sit telomeres — repeated stretches of a six-letter DNA sequence (TTAGGG, if you’re curious) that serve as protective caps. Think of the plastic tip on a shoelace. Without it, the lace unravels. Without telomeres, chromosomes fuse, degrade, and malfunction.
Here is the problem. Every time a cell divides, its telomeres get a little shorter. The molecular machinery that copies DNA simply cannot replicate the very end of a linear chromosome — it’s a geometric limitation, first described by the molecular biologist Alexei Olovnikov in 1971 and independently by James Watson. Over a lifetime of cell divisions, telomeres erode. When they get critically short, the cell either stops dividing — entering a dormant state called senescence — or dies.
Shortened telomeres have been linked in the research literature to cardiovascular disease, type 2 diabetes, certain cancers, weakened immune function, and earlier death. Researchers now treat telomere length as a biomarker of biological aging, which can diverge significantly from chronological age. Two people born the same year can have very different telomere lengths, and those differences correlate with health outcomes.
Telomerase is the enzyme that fights back. Elizabeth Blackburn and Carol Greider discovered it in 1984. It adds those TTAGGG repeats back onto the telomere ends, rebuilding the caps. It is the only enzyme in the body that can lengthen telomeres. That discovery — understanding how chromosomes protect themselves and how one enzyme can reverse their erosion — is what earned Blackburn the Nobel Prize.
The 2013 Trial: Omega-3, Oxidative Stress, and Telomere Length
Kiecolt-Glaser JK, Epel ES, Belury MA, Andridge R, Lin J, Glaser R, Malarkey WB, Hwang BS, Blackburn EH. Brain, Behavior, and Immunity. 2013;28:16–24. PubMed | Free full text
The question
Kiecolt-Glaser’s group had spent years documenting that psychological stress drives up inflammation and oxidative stress. Blackburn and Epel had shown those same forces chew away at telomeres. Could omega-3 supplementation — known to dampen inflammation — reduce oxidative stress enough to protect telomere length in actual humans, in a rigorous controlled trial?
The design
They ran a double-blind, placebo-controlled, randomized clinical trial at Ohio State — the gold standard. A hundred and six healthy but sedentary, overweight, middle-aged and older adults were randomly assigned to one of three groups for four months. The high-dose group took six capsules a day of OmegaBrite 7010MD, delivering 2,085 mg EPA and 348 mg DHA. The low-dose group took three capsules. The placebo group received capsules designed to mirror the fatty acid proportions of the typical American diet. All capsules were coated with fuchsia dye so participants couldn’t tell which group they were in.
The researchers chose OmegaBrite 7010MD specifically for its unique high 7:1 EPA-to-DHA ratio. Each 500 mg gel capsule contained 347.5 mg EPA and 58 mg DHA. They selected this ratio because the scientific literature pointed to EPA as having relatively stronger anti-inflammatory effects than DHA.
Blood was drawn at the start and after four months. The team measured leukocyte telomere length, telomerase activity, and F2-isoprostanes — a validated biomarker of oxidative stress and the current gold standard for measuring it in vivo.
What the data showed
Omega-3 supplementation lowered F2-isoprostanes by about 15 percent compared to placebo (p=0.02). That matters because oxidative stress directly damages telomeric DNA. Less oxidative stress means less telomere erosion.
The telomere finding was more nuanced and, arguably, more interesting. Group-level telomere differences did not reach statistical significance on their own. But when the researchers analyzed what actually changed in each participant’s blood — specifically, the ratio of omega-6 to omega-3 fatty acids in their plasma — a clear pattern emerged. As that ratio dropped (meaning more omega-3 relative to omega-6), telomere length went up. Each 1-unit decrease corresponded to roughly 20 additional base pairs of telomere length (p=0.02).
That may sound abstract. Here’s a way to think about it. Human white blood cell telomeres lose an estimated 15 to 30 base pairs per year of normal aging. So a 1-unit improvement in the fatty acid ratio offset approximately one year of typical telomere attrition.
In the placebo group, telomeres shortened over the four months — consistent with normal aging. Participants who took omega-3 and whose fatty acid ratio improved maintained or even lengthened theirs.
Why the ratio mattered more than the number of capsules
This is a subtle but important point. The study did not find that swallowing omega-3 capsules automatically lengthened everyone’s telomeres. What it found was that the degree of change in the omega-6-to-omega-3 ratio — which varied from person to person depending on absorption, baseline diet, metabolism, and other individual factors — was the real predictor.
The typical Western diet delivers an omega-6-to-omega-3 ratio somewhere around 15:1 to 20:1. Ancestral human diets are estimated at 2:1 to 4:1. Omega-6 fatty acids promote inflammatory signaling. Shifting the ratio toward omega-3 reduces chronic low-grade inflammation, and that reduction is what protects telomeres. The benefit is biological, not arithmetic. It depends on actually changing the fatty acid composition in your cells, not just counting pills.
The 2021 Follow-Up: Omega-3 Preserves Telomerase Under Stress
Madison AA, Belury MA, Andridge R, Renna ME, Shrout MR, Malarkey WB, Lin J, Epel ES, Kiecolt-Glaser JK. Molecular Psychiatry. 2021;26(7):3034–3042. PubMed
A harder question
The 2021 study, led by Annelise Madison with Kiecolt-Glaser as senior author and Epel and Lin as co-authors, went after something more specific. What happens to telomerase — the repair enzyme itself — when the body is under acute stress?
This matters because stress is not just an unpleasant feeling. At the cellular level, psychological stress activates the hypothalamic-pituitary-adrenal axis, flooding the body with cortisol. Pro-inflammatory cytokines like IL-6 spike. And as this study would show, telomerase activity drops. The one enzyme that can rebuild telomeres gets suppressed at exactly the moment stress is doing the most damage to them.
The stress test
Participants from the same parent trial — 138 in this analysis, drawn from a larger pool than the 106 in the telomere substudy — underwent the Trier Social Stress Test, or TSST — a validated protocol in which people must deliver an impromptu speech in front of stone-faced evaluators and then perform difficult mental arithmetic out loud. It is the gold standard for inducing acute psychological stress in a laboratory. They did it twice: once at baseline and once after four months of supplementation.
Blood was drawn at multiple time points — before, during, and after the stressor — and the researchers measured telomerase activity, IL-6, IL-10 (an anti-inflammatory cytokine), and cortisol.
The results
In the placebo group, telomerase activity plummeted about 24 percent after the stress test. The body’s only telomere-repair enzyme was being suppressed at the very moment it was most needed.
In both omega-3 groups — whether taking three or six capsules a day — telomerase held steady through the stress challenge. It simply was not suppressed. The authors described this finding as robust.
The anti-inflammatory cytokine IL-10 told a similar story. The placebo group’s IL-10 dropped about 18 percent from pre-stress levels by two hours after the stressor, leaving them with IL-10 levels 26 percent lower than the high-dose omega-3 group at that time point. Both omega-3 groups were protected — their IL-10 did not decline.
At the higher dose, the benefits extended further. Participants taking six capsules a day had cortisol levels 19 percent lower than placebo and IL-6 levels 33 percent lower. The three-capsule dose preserved telomerase and IL-10 but did not significantly move cortisol or IL-6, which suggests a dose-response relationship for the broader stress-buffering effects.
What this tells us
When you are under stress, your body suppresses the one enzyme that can repair age-related chromosomal damage. This trial showed that high-EPA omega-3 supplementation prevented that suppression. At the higher dose, it also tamped down the stress hormones and inflammatory signals doing the damage in the first place. This was not a survey or an observational study. It was a randomized, controlled, blinded trial with an objective stressor and blood-based biomarkers. Mechanistic evidence, not correlation.
Blackburn’s Book: The Telomere Effect
In The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer (Grand Central Publishing, 2017), Blackburn and Epel translate the telomere science for a general audience. They identify three cellular enemies of telomere health — inflammation, oxidative stress, and insulin resistance — and name omega-3-rich nutrition and a balanced omega-6-to-omega-3 ratio among the lifestyle tools that help protect telomeres. They place omega-3s alongside exercise, sleep, stress management, and meditation.
The Kiecolt-Glaser trials tested exactly those pathways. The 2021 study went further, demonstrating that omega-3 preserved the very enzyme Blackburn discovered under the pressure of acute stress.
Understanding the Mechanism: Why EPA?
The results from these trials — lower oxidative stress, preserved telomerase, reduced IL-6 and cortisol — trace back to well-characterized molecular pathways. Understanding them helps explain not only the telomere data but why a high-EPA omega-3 might matter for stress, mood, cognition, and inflammation more broadly.
Competing with arachidonic acid
In 1982, Sune Bergström, Bengt Samuelsson, and John Vane received the Nobel Prize in Physiology or Medicine for working out how arachidonic acid — an omega-6 fatty acid embedded in cell membranes — gets converted by COX and LOX enzymes into prostaglandins, thromboxanes, and leukotrienes. These molecules are the chemical mediators of inflammation and pain.
EPA is a structural analog of arachidonic acid. It competes for those same enzymes. When EPA displaces arachidonic acid at the enzyme’s active site, the output shifts. Instead of pro-inflammatory mediators, the body produces anti-inflammatory and inflammation-resolving molecules — series-3 prostaglandins and resolvins among them. The higher the EPA concentration in your cell membranes, the more effectively it wins that competition. This is one reason the EPA-to-DHA ratio matters: EPA is the omega-3 that directly displaces the inflammatory substrate.
PPARγ and nuclear signaling
EPA also acts inside the cell nucleus. It activates PPARγ — peroxisome proliferator-activated receptor gamma — a nuclear receptor that directly suppresses NF-κB, the master transcription factor controlling inflammatory gene expression. This is not a surface-level event. A dietary fatty acid enters the nucleus and changes which genes get turned on. It represents a second anti-inflammatory pathway, additive to the arachidonic acid competition, operating at the level of gene transcription.
The chain runs from EPA activating PPARγ to suppression of NF-κB to lower levels of IL-6 and TNF-α to reduced oxidative stress to less damage to telomeric DNA to preserved telomere length and telomerase activity. Every outcome Kiecolt-Glaser’s team measured sits downstream of these converging pathways.
The cytokine cascade and the brain
The same inflammatory molecules that damage telomeres cross the blood-brain barrier. IL-6 and TNF-α activate microglia, the brain’s resident immune cells, triggering neuroinflammation. Chronic neuroinflammation is now recognized across the psychiatric and neurological literature as a contributor to depression, anxiety, cognitive decline, and accelerated brain aging.
By reducing systemic inflammation through both arachidonic acid displacement and PPARγ-mediated gene suppression, a high-EPA omega-3 addresses neuroinflammation at its origin. That is the mechanistic basis for the clinical observations — improvements in mood, anxiety, stress resilience, and cognitive clarity — that have been associated with high-EPA supplementation across multiple lines of research.
What This Means For You
In NIH-funded trials at Ohio State, conducted in collaboration with UCSF, the high‑EPA omega‑3 formulation OmegaBrite 7010MD helped the body stay in a more anti-inflammatory, repair-supporting state during stress — improving the omega‑6:omega‑3 ratio, slowing telomere shortening, preserving telomerase and IL‑10, and, at higher doses, lowering IL‑6 and cortisol.
In practical terms, this suggests that taking OmegaBrite 7010MD as part of a healthy lifestyle may help your cells cope better with stress:
- Helps improve the omega‑6:omega‑3 balance in your blood, shifting away from a pro‑inflammatory pattern.
- Helps slow or prevent stress‑related telomere shortening, a biomarker linked to biological aging.
- Helps preserve telomerase, the enzyme that helps repair your telomeres and protect your cells.
- Helps preserve levels of IL‑10, an anti‑inflammatory molecule that supports a healthier immune response and brain environment.
- At 6 capsules a day, helps lower pro‑inflammatory IL‑6 and lower cortisol, the body’s main stress hormone that, when chronically elevated, can harm sleep, mood, metabolism, and brain health.
Used alongside sleep, exercise, and stress‑management practices, OmegaBrite 7010MD offers a science‑based way to support healthy stress resilience and cellular aging.
(Disclosure: Dr. Carol Locke, MD, is the founder and formulator of OmegaBrite. OmegaBrite supplied supplements and placebos as unrestricted gifts and had no role in study design, analysis, or publication. All studies were independently funded by the National Institutes of Health.)
