Inflammation rises with age in modern societies, but two Indigenous groups broke the pattern

Key takeaways

• In a 2025 study in Nature Aging, a blood signature of age-related inflammation held up in Italy and Singapore but barely tracked age in two Indigenous groups, where inflammation followed infections instead¹².
• In a 2014 study of 17,182 people, about 1 in 10 people in their 70s and nearly 1 in 5 people 90 and older had mutated blood stem cells, called CHIP, and carriers had about twice the risk of coronary heart disease⁵.
• No cardiology society recommends routine CHIP testing for people without symptoms; most cases are found by chance, by blood or cancer specialists checking something else⁷.
• Exercise lowered the inflammation marker CRP across 83 trials, more so when weight came down, but in adults 60 and older the average drop was tiny⁹¹⁰.
• In 2023, the FDA approved low-dose colchicine, first approved for gout in 1961, to cut heart risk; in its main trial in stable coronary disease, major heart events fell from 9.6% to 6.8%¹²¹⁴.

In the Bolivian Amazon, about two in three Tsimane in one study carried at least one intestinal parasite¹. Their immune systems stay busy, and their blood shows it¹.

Yet when scientists checked how inflammation changed with age, the Tsimane broke a pattern seen in industrialized countries¹². So did the Orang Asli of Peninsular Malaysia, more than 70% of whom had a current infection¹.

The team, which included Alan Cohen of Columbia University, built an inflammation score from 19 immune-signaling proteins measured in an Italian aging study¹². In Singapore, the score behaved much the same way. Among the Tsimane and the Orang Asli, it had little or no link to age and none to the diseases of aging².

Diabetes, heart disease and Alzheimer’s were rare or largely absent in those two groups¹. The authors concluded that age-related inflammation, measured this way, looks “largely a byproduct of industrialized lifestyles”².

If modern living drives much of the rise, some of it may be changeable. Here is what drives it, a surprising source inside your own blood, and what has lowered it in trials.

Inflammaging is a slow burn, and IL-6 is its best-known signal

Scientist Claudio Franceschi coined the word “inflammaging” in a paper published in 2000⁴. It describes chronic, low-grade inflammation that tends to build in older people and is tied to illness and death⁴.

Short bursts of inflammation fight infection and heal injuries. Our article on anti-inflammatory claims explains that difference, along with the CRP blood test doctors use to gauge heart risk. The concern here is a quieter rise that lasts for years.

Researchers track it through cytokines, the small proteins immune cells use to signal one another. Interleukin-6, or IL-6, is the one most often tied to aging and death, according to a 2022 review in Frontiers in Aging by Carey Shive and Pushpa Pandiyan⁴. CRP and a signal called TNF-alpha also tend to run higher⁴.

The review gathers several warning signs. Among 1,293 older adults with no disability, those with higher IL-6 and CRP levels had higher death rates, heart deaths in particular⁴. A study of older veterans found that frailty lined up better with inflammation than with birthdays⁴. And in people past 80 who were in fairly good health, high IL-6 signaled a shorter life⁴.

These observational studies show that inflammation travels with decline, not that it causes it. Illness can raise inflammation, too.

Many forces feed the burn. The review lists aging cells that stop dividing but keep sending inflammatory signals, lifelong viral infections such as cytomegalovirus, DNA damage and a less diverse gut microbiome⁴. A companion article in this series covers those aging “zombie cells” in depth.

The Amazon result is a clue, not a recipe

The 2025 study has real limits. It appeared as a short letter, which leaves little room to discuss weaknesses, noted immunologist Antonio J. Ruiz Alcaraz of Spain’s University of Murcia, though he judged the work good quality³. It tested just two nonindustrialized groups².

The authors also stressed that there’s no agreed way to measure inflammaging with blood proteins². Keep that in mind if a company offers you a consumer “inflammation panel,” and see our article “When the company reading your labs also sells the fix.”

Nor is life in the Amazon something to copy wholesale. Tsimane inflammation runs high partly because infections are so common¹. Cohen suggested that the pattern in rich countries may reflect a mismatch between immune systems shaped in one world and the modern one we live in now¹.

That idea fits what many natural-health readers already sense: some of what we call “normal aging” may be the cost of modern habits. Cohen pointed to factors such as high physical activity and a very low-fat diet as possible influences on how immune systems age¹. Notably, Franceschi, who coined the term, is a coauthor of the study questioning how universal it is².

A hidden driver: blood stem cells that collect mutations

The second surprise came from cancer research. Your bone marrow holds stem cells that make every blood cell. Over a lifetime, some pick up DNA changes, called mutations, that let them out-copy their neighbors.

When one of these mutated cell families grows large without causing blood cancer, doctors call it clonal hematopoiesis of indeterminate potential, or CHIP⁷. The line sits at 2%: the mutation has to turn up in at least that share of the gene copies a lab reads from the blood. Cleveland Clinic authors of a 2026 review note that the cutoff is arbitrary⁷.

In 2014, Jaiswal and colleagues reported on blood DNA from 17,182 people in the New England Journal of Medicine⁵. These mutations were very rare before 40. They appeared in 5.6% of people in their 60s, 9.5% in their 70s, 11.7% in their 80s and 18.4% of those 90 and older⁵.

Later estimates run higher. The 2026 review puts CHIP at about 17% of people in their 60s and about 30% by age 80⁷. Studies read blood DNA with different methods and depths, which likely explains much of the gap (our reading).

Carriers in the 2014 study had 11 times the risk of blood cancer⁵. In absolute terms, that came to about 0.5% a year, and about 4% of carriers developed a blood cancer during the study⁵. Most carriers never do.

The bigger surprise was the heart. Carriers had about twice the risk of coronary heart disease, 2.6 times the risk of the most common type of stroke and a 40% higher risk of death from any cause⁵.

Mutated blood cells may inflame artery walls

In 2017, Jaiswal’s group tested the heart link more directly⁶. Across four studies with 4,726 people who had coronary heart disease and 3,529 who didn’t, CHIP came with about 1.9 times the risk of coronary disease⁶. In people who had a heart attack at a young age, it came with about 4 times the risk⁶.

Then the team turned to mice prone to clogged arteries. Mice given bone marrow with a disabled Tet2 gene, the second most commonly mutated CHIP gene, grew larger artery plaques⁶. Their immune cells made more of the signals that promote plaque⁶.

The suspected chain runs through inflammation. TET2 mutations switch on an inflammatory alarm inside immune cells, called the NLRP3 inflammasome, which ramps up IL-1 beta and IL-6⁷.

People offer a natural experiment, too. Some inherit a gene version that dampens IL-6 signaling. Among CHIP carriers with DNMT3A or TET2 mutations, that built-in dampening went with substantially lower heart risk, a 2022 review in Current Cardiology Reports notes⁸.

The Cleveland Clinic review gives absolute numbers from the Women’s Health Initiative. Over 10 years, coronary heart disease struck 13.6% of women with TET2 CHIP and 9.0% of women without it⁷. By our arithmetic, that’s about 4.6 more cases per 100 women.

Should you get tested for CHIP? Not routinely, for now

No cardiology group currently tells doctors to screen symptom-free adults for CHIP, the Cleveland Clinic review says⁷. Spotting it requires deep DNA sequencing of a blood sample, and that test isn’t part of standard care yet⁸.

Most people learn they have CHIP by chance, from a blood or cancer specialist checking something else⁷. Some academic centers now run CHIP clinics, where hematologists watch for blood cancer and cardiologists manage heart risk⁷.

For people with CHIP, the review’s advice sounds familiar: regular activity, a Mediterranean-style diet, weight loss if needed and quitting smoking, plus closer attention to cholesterol, blood pressure and blood sugar⁷. Whether intensive cholesterol-lowering helps these patients more than others is still unknown⁷.

Researchers are testing targeted treatments, including colchicine in people with CHIP and coronary disease, and drugs that block the NLRP3 alarm⁷. The review also says people with TET2 CHIP may discuss vitamin C with their doctors, citing lab evidence that it helps TET2-mutant cells remove chemical tags from their DNA⁷. That’s an idea under study, not a reason to buy high-dose vitamin C.

Can habits affect who develops CHIP? Smoking has been linked to it, mostly in current smokers, though not consistently⁸. In one large study, women at a normal weight had CHIP less often than women with obesity⁸. Diet studies disagree, and cancer treatments such as chemotherapy and radiation show the strongest links⁸.

The inflammaging levers you can pull

This table is our own summary of the main drivers. The rating describes how well it has been tested that changing each driver lowers inflammation markers, not whether doing so adds years of life.

Driver	Evidence it raises inflammation	What lowers it	Rating
Industrialized way of life	The age-linked pattern appeared in Italy and Singapore, not in two Indigenous groups12	Not tested as a package	Not enough evidence
Extra body fat	CRP fell more in exercise trials when weight dropped9; obesity was tied to more CHIP in women8	Diet-driven weight loss lowered CRP, IL-6 and a TNF marker over 18 months11	Strong evidence, for markers
Inactivity	Exercise training lowered CRP across 83 trials9	Regular aerobic or strength training910	Strong evidence, small effect
Smoking	Linked to CHIP, mostly in current smokers; not every study agrees8	Quitting; its effect on CHIP is untested	Not enough evidence, for CHIP
Chronic infections	Inflammation tracked infection in the Tsimane and Orang Asli1; lifelong viral infections are a listed driver4	Not tested as an anti-aging strategy	Not enough evidence
Mutated blood cells (CHIP)	Tied to heart disease through IL-1 beta and IL-667	Drug trials under way7	Not enough evidence

Diet, the gut barrier and sleep have their own articles in this library, and a later article in this series covers belly fat.

Exercise and weight loss move the markers, but only a little

A 2017 analysis in the British Journal of Sports Medicine pooled 83 trials with 3,769 people⁹. Exercise training lowered CRP regardless of age or sex⁹. The drop was larger when body mass index came down, but it still showed up without weight loss⁹.

For older adults, the numbers are humbler. A 2026 review of 19 randomized trials in people 60 and older found that exercise cut CRP by an average of 0.07 mg/L, with small drops in IL-6 and TNF-alpha¹⁰. Results varied widely between studies, and no trial could hide from people whether they were exercising¹⁰.

One 18-month trial is especially telling. Researchers randomly assigned 316 sedentary adults 60 and older, all with overweight or obesity and knee arthritis, to diet-driven weight loss, exercise, both, or a healthy-lifestyle control group¹¹.

Weight loss lowered CRP, IL-6 and a TNF receptor marker more than no weight loss did¹¹. Exercise alone, an hour of walking and weight training three times a week, didn’t significantly change any of them¹¹.

None of this means exercise is wasted on aging bodies. Our article on activity doses covers its links to lower risk of cancer, depression, dementia and early death. But in that trial, losing excess fat did more for the inflammation numbers than workouts alone.

One anti-inflammatory pill earned FDA approval for the heart

In June 2023, the FDA approved Lodoco, a low-dose colchicine tablet, to cut the risk of heart attack, stroke, artery-opening procedures and heart-related death¹². It’s meant for adults who already have artery disease or several heart risk factors¹².

The approval rested on one large trial, LoDoCo2, in 5,522 people with stable coronary disease who took 0.5 mg a day or a placebo¹². Over a median of 28.6 months, major heart events struck 9.6% of the placebo group and 6.8% of the colchicine group¹⁴¹⁵. By our arithmetic, that’s about 3 fewer events per 100 people, or roughly 36 people treated to prevent one.

There was a worrying signal. Deaths not caused by heart disease numbered 53 on colchicine and 35 on placebo, a gap just short of statistical significance¹⁴. Deaths from any cause didn’t differ meaningfully¹⁴.

Other trials have been less encouraging. In two large trials in stroke patients, CONVINCE and CHANCE-3, colchicine didn’t significantly reduce events¹⁵. A large trial in heart attack patients was also neutral, as our article on anti-inflammatory claims describes.

Colchicine’s label rules it out for people with kidney failure, severe liver disease or existing blood disorders¹³. It also rules out strong drugs that block the liver enzyme CYP3A4 or a drug pump called P-gp, because deadly colchicine toxicity has been reported with them¹³. The label warns of blood disorders and nerve and muscle toxicity, and lists diarrhea, vomiting, cramps and muscle pain as the most common side effects¹³.

So colchicine is a heart medicine for people with heart disease, prescribed and monitored by a clinician. It hasn’t been tested as a way to slow aging in healthy people.

How strong is the evidence?

Claim	Rating	Why
Inflammation markers rise with age in industrialized countries and track with frailty and death	Strong evidence (observational)	Consistent links in cohort studies4
Age-related inflammation is mostly a product of industrialized life	Promising but early	One four-population study in a short format23
CHIP raises the risk of heart disease	Strong evidence (observational, with animal experiments)	Large genetic studies and mouse tests56
Routine CHIP testing helps people without symptoms	Not enough evidence	No guideline recommends it7
Exercise lowers CRP	Strong evidence of a small effect	83 trials; a tiny average drop in older adults910
Weight loss lowers inflammation markers in older adults with obesity	Strong evidence (for markers)	An 18-month randomized trial; pooled exercise trials also saw bigger CRP drops when weight fell911
Colchicine cuts heart events in stable coronary disease	Strong evidence	One large placebo-controlled trial, accepted by the FDA1214
Colchicine prevents repeat events after a stroke	Evidence says no, or unsafe	Two large stroke trials missed their main goals15

Questions readers ask

The bottom line

Inflammation that creeps up with age is real, measurable and tied to frailty, heart disease and death in industrialized countries. A 2025 study suggests much of that rise reflects how modern people live rather than aging itself, though that evidence is early. Part of it also comes from mutated blood stem cells, a common finding with age that roughly doubles heart risk but doesn’t call for routine testing.

What lowers inflammation markers is mostly familiar: losing excess fat and staying active, with modest effects on the numbers. For people with heart disease, one low-dose prescription drug now has FDA approval. For everyone else, the best-tested steps are still the everyday ones.

Related reading

• Inflammation can harm your heart, but an “anti-inflammatory” label proves little
• Leaky gut can be measured, but most “heal your gut” protocols haven’t been tested
• Eight healthy eating patterns faced a 30-year test and mostly agreed
• Activity tracks with lower risk of 13 cancers, and even one-minute bursts count
• When the company reading your labs also sells the fix

Sources

1. Columbia University Mailman School of Public Health. “Aging-Related Inflammation Is Not Universal Across Human Populations.” News release, June 30, 2025. publichealth.columbia.edu
2. Franck M, Tanner KT, Tennyson RL, et al., Ferrucci L, Franceschi C, Gurven M, Cohen AA. “Nonuniversality of Inflammaging Across Human Populations.” Nature Aging, 2025;5:1471–1480 (Toulouse School of Economics record). tse-fr.eu
3. Science Media Centre Spain. Expert reaction by Antonio J. Ruiz Alcaraz, University of Murcia, to Franck M, et al., Nature Aging, June 30, 2025. sciencemediacentre.es
4. Shive C, Pandiyan P. “Inflammation, Immune Senescence, and Dysregulated Immune Regulation in the Elderly.” Frontiers in Aging, 2022;3:840827. frontiersin.org
5. Jaiswal S, et al. “Age-Related Clonal Hematopoiesis Associated With Adverse Outcomes.” New England Journal of Medicine, 2014;371(26):2488–2498 (Dana-Farber Cancer Institute, Ebert Lab copy). labs.dana-farber.org
6. Jaiswal S, et al. “Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease.” New England Journal of Medicine, 2017;377 (University of Cambridge repository). repository.cam.ac.uk
7. Oren O, Laffin LJ, Singh A, Nissen SE, Carraway HE. “Clonal Hematopoiesis of Indeterminate Potential and Heart Disease: What Every Internist Needs to Know.” Cleveland Clinic Journal of Medicine, 2026;93(5):289. ccjm.org
8. Haring B, Wissel S, Manson JE. “Somatic Mutations and Clonal Hematopoiesis as Drivers of Age-Related Cardiovascular Risk.” Current Cardiology Reports, 2022 (Saarland University repository). pubmed.ncbi.nlm.nih.gov
9. Fedewa MV, Hathaway ED, Ward-Ritacco CL. “Effect of Exercise Training on C Reactive Protein: A Systematic Review and Meta-Analysis of Randomised and Non-Randomised Controlled Trials.” British Journal of Sports Medicine, 2017;51(8):670. pubmed.ncbi.nlm.nih.gov
10. Liu Y, Mao S, Xie W, et al. “Effect of Exercise on Abdominal Obesity and Inflammatory Response in the Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Frontiers in Sports and Active Living, published January 6, 2026. frontiersin.org
11. Nicklas BJ, Ambrosius W, Messier SP, et al. “Diet-Induced Weight Loss, Exercise, and Chronic Inflammation in Older, Obese Adults: A Randomized Controlled Clinical Trial.” American Journal of Clinical Nutrition, 2004;79(4):544–551 (University of Arizona record). experts.arizona.edu
12. U.S. Food and Drug Administration. “Lodoco (Colchicine) Tablets, NDA 215727: Other Reviews.” Drugs@FDA, 2023. accessdata.fda.gov
13. Agepha Pharma USA. “Lodoco (Colchicine) Tablets, for Oral Use: Full Prescribing Information” (FDA-approved label). Revised June 2023. lodoco.com
14. 2 Minute Medicine. “Colchicine May Lower the Risk of Cardiovascular Events in Patients With Coronary Disease” (on Nidorf SM, et al., LoDoCo2, New England Journal of Medicine, 2020). September 1, 2020. 2minutemedicine.com
15. Animati FM, Cappannoli L, Proietti S, et al. “Colchicine in Coronary Artery and Cerebrovascular Disease: ‘Old Skin for the New Ceremony.'” World Journal of Cardiology, 2025;17(11):110563 (Table 1). pubmed.ncbi.nlm.nih.gov