What is inflammageing? The Silent Fire That Ages You From the Inside Out

If you are over 40 and feel like your body is ageing faster than it should — more joint stiffness, slower recovery, brain fog that was not there five years ago, stubborn weight around the middle — there is a very good chance something is happening beneath the surface that no one has explained to you.

It is called inflammageing.

Not a disease. Not a diagnosis your GP will hand you. It is something more insidious than that: a slow, chronic, low-grade inflammatory state that builds silently across decades, accelerating every single hallmark of biological ageing. And the uncomfortable truth is that most people over 40 are already experiencing it without knowing. Their blood work might look "normal." They might not have any named condition. But the fire is burning.

I have spent over fifteen years working in functional health, and inflammageing is the pattern I see more than any other. It shows up in the bloods, in the symptoms, in the way people describe feeling older than their years. Once you understand it, you cannot unsee it. And once you know how to measure it and intervene, the trajectory can change dramatically.

Let me walk you through what is actually going on.

Where the Term Comes From

Inflammageing was first described in 2000 by Italian immunologist Claudio Franceschi and his research team at the University of Bologna. They published a landmark paper in the Annals of the New York Academy of Sciences arguing that a progressive increase in proinflammatory status is a core characteristic of the ageing process — not a side effect of it. They called this phenomenon "inflamm-aging" and framed it as the result of a lifetime of accumulated antigenic load and stress.

What Franceschi identified was not acute inflammation — the kind you get from a cut or an infection, which resolves. It was something different: a chronic, low-grade, sterile inflammation that operates systemically, without a clear infectious trigger, and never fully resolves. A two- to fourfold elevation in circulating inflammatory mediators that persists year after year, gradually degrading tissue function and immune competence.

More than two decades of research since then has confirmed and expanded this framework. Inflammageing is now recognised as one of the central mechanisms connecting immune decline with the broader biology of ageing.

The Self-Reinforcing Loop

What makes inflammageing so difficult to escape once it takes hold is that it operates as a self-amplifying cycle. Multiple systems feed into it, and it feeds right back into them.

Senescent cells accumulate as you age. These are damaged cells that have stopped dividing but refuse to die. Instead, they sit in your tissues secreting a cocktail of proinflammatory cytokines, chemokines, and proteases — collectively called the senescence-associated secretory phenotype, or SASP. A young immune system clears these cells efficiently. An ageing immune system does not. So they pile up, and the inflammatory signalling they produce becomes a constant background hum.

Gut permeability increases. The intestinal barrier, which is supposed to be selectively permeable, becomes compromised — what many people know as "leaky gut." Bacterial endotoxins like lipopolysaccharide (LPS) translocate into the bloodstream, triggering immune activation that has nothing to do with an actual infection. This is one of the key mechanisms behind the "sterile" part of sterile inflammation.

Mitochondrial dysfunction accelerates the problem. As mitochondria become less efficient, they generate more reactive oxygen species and release fragments of mitochondrial DNA into the cytoplasm. These fragments are recognised by the innate immune system as danger signals — because mitochondrial DNA is ancient bacterial DNA — and they activate inflammatory pathways, particularly the NLRP3 inflammasome. So your own cellular power plants are now generating inflammatory signals.

Immune dysregulation completes the loop. The adaptive immune system becomes less precise. T-cell diversity narrows. Natural killer cell function declines. Meanwhile, the innate immune system becomes hyperactivated — primed to fire but less able to resolve. The result is more inflammation with less ability to clean it up.

Each of these systems amplifies the others. Senescent cells damage the gut lining. A permeable gut drives further immune activation. Immune activation damages mitochondria. Damaged mitochondria promote cellular senescence. Round and round it goes.

Inflammageing and the Hallmarks of Ageing

If you follow longevity science, you will have come across the hallmarks of ageing — a framework published in 2013 and updated in 2023 that categorises the biological processes driving ageing into interconnected pillars. Inflammageing does not sit neatly in one pillar. It cuts across almost all of them.

Genomic instability: chronic inflammation generates reactive oxygen species that damage DNA directly, accelerating the accumulation of mutations and epigenetic drift.

Telomere attrition: inflammatory cytokines, particularly TNF-alpha and IL-6, accelerate telomere shortening in immune cells and other proliferating tissues.

Mitochondrial dysfunction: as described above, damaged mitochondria both cause and are caused by inflammageing, creating a bidirectional feedback loop.

Cellular senescence: SASP from senescent cells is one of the primary engines of chronic inflammation in ageing tissues, and chronic inflammation in turn promotes the senescent phenotype in neighbouring cells.

Altered intercellular communication: inflammageing is, at its core, a disorder of cellular communication — inflammatory signalling that should be transient becomes permanent, reprogramming tissue behaviour across the body.

This is why inflammageing is not just one more item on a list of things that go wrong as you age. It is the connective tissue between them. Address inflammageing and you create downstream benefits across multiple hallmarks simultaneously.

How to Measure Inflammageing

One of the most empowering things about inflammageing is that it is measurable. You do not have to guess whether it is happening. A combination of standard and functional blood markers can give you a clear picture of your inflammatory trajectory.

High-sensitivity C-reactive protein (hs-CRP) is the most widely available marker. It reflects systemic inflammation and is easily ordered through any GP. Optimal is below 1.0 mg/L. Between 1.0 and 3.0 indicates moderate chronic inflammation. Above 3.0 is a red flag.

Interleukin-6 (IL-6) is one of the key proinflammatory cytokines in the inflammageing cascade. Elevated IL-6 is associated with accelerated biological ageing, sarcopenia, insulin resistance, and cognitive decline. This one typically requires a functional or integrative practitioner to order.

Tumour necrosis factor-alpha (TNF-alpha) is another central driver. Elevated TNF-alpha is implicated in virtually every age-related inflammatory condition.

The neutrophil-to-lymphocyte ratio (NLR) is a powerful and underused tool that can be calculated from a standard complete blood count — something nearly everyone has had done. It reflects the balance between innate immune activation (neutrophils) and adaptive immune competence (lymphocytes). An NLR above 3.0 suggests a proinflammatory shift. Above 4.0 and you are looking at significant immune dysregulation.

This is actually one of the reasons we developed MyImmuneAge (myimmuneage.life) — to give people a way to track their immune resilience over time using a composite Immune Resilience Index built from six CBC-derived biomarker ratios, including NLR. It takes data most people already have from routine blood tests and turns it into a meaningful, trackable score. No exotic testing required.

What Accelerates Inflammageing

The inflammatory load on your body is not fixed. It is shaped by how you live. Several factors reliably accelerate the inflammageing process.

Poor sleep is one of the most potent drivers. Even a few nights of short or disrupted sleep measurably elevates IL-6 and CRP. Chronic sleep restriction fundamentally alters immune function toward a proinflammatory phenotype.

Metabolic syndrome — the cluster of insulin resistance, central obesity, elevated triglycerides, hypertension, and low HDL — is both a cause and a consequence of inflammageing. Visceral fat is not inert storage tissue. It is an endocrine organ that actively secretes inflammatory cytokines. The more visceral fat you carry, the higher your baseline inflammatory load.

Gut dysbiosis disrupts the intestinal barrier and shifts the microbiome toward proinflammatory species that produce more LPS and fewer short-chain fatty acids. The gut-immune axis is arguably the single most important interface in the inflammageing story because roughly 70 percent of your immune system is gut-associated.

Chronic psychological stress activates the HPA axis and the sympathetic nervous system in ways that directly upregulate NF-kB, the master transcription factor for inflammatory gene expression. Stress does not just feel bad — it is literally proinflammatory at the molecular level.

Sedentary behaviour allows inflammatory mediators to accumulate unopposed. Skeletal muscle is an anti-inflammatory organ when used — contracting muscles release myokines like IL-10 and IL-1 receptor antagonist that actively dampen inflammation. Stop moving and you lose that counterbalance.

Ultra-processed food delivers a combination of excess omega-6 fatty acids, advanced glycation end products, emulsifiers that damage the gut lining, and caloric excess that drives metabolic dysfunction — all of which feed the inflammageing fire.

What Slows Inflammageing Down

The good news is that every one of those accelerators has a corresponding intervention. And because inflammageing is a loop, breaking the cycle at any point creates cascading benefits.

Exercise is the single most powerful anti-inflammageing intervention available. Regular moderate-to-vigorous physical activity reduces hs-CRP, IL-6, and TNF-alpha while increasing anti-inflammatory myokines. Resistance training is particularly important because it builds the muscle mass that serves as your primary anti-inflammatory organ. I have run more than 70,000 kilometres in my career as an ultra-endurance athlete, and while I would not recommend that volume to anyone, I can tell you from personal experience and clinical observation that consistent, intelligent movement is non-negotiable for anyone serious about slowing biological ageing.

Sleep optimisation — seven to eight hours of quality sleep in a dark, cool room with consistent timing — is foundational. Nothing else works properly if your sleep is broken.

Gut health restoration through dietary fibre, fermented foods, polyphenol-rich plants, and strategic probiotic and prebiotic support rebuilds the intestinal barrier and shifts the microbiome toward anti-inflammatory species.

Stress management — and I mean genuine nervous system regulation, not just "trying to relax" — directly reduces NF-kB activation and HPA axis overdrive. Breathwork, meditation, cold exposure, time in nature: pick what works for you and do it consistently.

Targeted Supplementation for Inflammageing

Beyond lifestyle, there are specific compounds with strong mechanistic rationale for targeting the inflammageing cascade directly. I want to highlight the ones I use in my own practice and in my own protocol.

Kawakawa (Piper excelsum) is a native New Zealand plant that has been used in traditional Maori rongoā for centuries and is now backed by emerging clinical research. Kawakawa modulates COX-2, the inflammatory enzyme that is chronically upregulated in ageing tissues, while preserving the normal prostaglandin signalling the body needs. It also regulates key cytokines — research has shown it downregulates IL-6 and TNF-alpha while upregulating the anti-inflammatory cytokine IL-10. That cytokine shift — from a proinflammatory to a regulated immune profile — is exactly what we are trying to achieve in addressing inflammageing. I have written extensively about the research on kawakawa here: lisatamati.com/blog/post/163229/kawakawa-benefits-research/

Carnosic acid, derived from rosemary, is a potent activator of the NRF2 pathway — the master switch governing more than 200 cytoprotective and antioxidant genes. NRF2 activity declines with age and is suppressed by chronic inflammation, so restoring it helps break the inflammageing loop from the oxidative stress side.

Colostrum extract (Immunel) at clinical dosing provides immunoglobulins, lactoferrin, and growth factors that support intestinal barrier integrity and modulate gut-associated immune function — directly addressing the gut permeability component of the inflammageing cascade.

Immune Defense Protein (IDP) supports innate immune surveillance, helping the body maintain efficient clearance of senescent cells and damaged tissue — one of the key failure points in the ageing immune system.

Fisetin and quercetin are two of the most researched senolytic compounds — meaning they selectively promote the clearance of senescent cells. By reducing the senescent cell burden, they reduce the SASP-driven inflammatory signalling that is one of the primary engines of inflammageing.

This is exactly why we formulated Re:juvenate Pro the way we did. Rather than targeting a single pathway, it was designed to address the inflammageing cascade across the gut-immune axis — combining kawakawa for COX-2 modulation and cytokine regulation, carnosic acid for NRF2 activation, Immunel at clinical dose for gut barrier and immune support, and IDP for innate immune function. It was developed with a US-based longevity medicine specialist specifically to intervene across the mechanisms that matter, not just tick a marketing box.

To my knowledge, it is the only supplement formulated and manufactured in New Zealand that specifically targets inflammageing across these interconnected pathways. You can learn more about Re:juvenate Pro here: shop.lisatamati.com/pages/rejuvenate (link opens in new window).

Where to Start

If inflammageing is new to you, here is what I would suggest:

Get a baseline. Ask your GP for an hs-CRP and a full CBC. Calculate your NLR from the results. If you want a more complete picture, work with a functional health practitioner who can order IL-6, TNF-alpha, and a comprehensive metabolic panel.

Track it over time. A single snapshot tells you less than a trend. This is where tools like MyImmuneAge can be genuinely useful — turning routine blood work into a trackable immune resilience score that shows you whether your interventions are actually working.

Address the foundations first. Sleep, movement, gut health, stress management. These are not nice-to-haves. They are the non-negotiable base layer.

Add targeted supplementation. Once the foundations are in place, compounds that directly modulate inflammatory signalling, support gut barrier integrity, and promote senescent cell clearance can meaningfully accelerate your progress.

Inflammageing is not inevitable. It is a biological process with identifiable drivers and measurable markers. The earlier you catch it and the more precisely you intervene, the more leverage you have over how you age. That is the real promise of longevity science — not adding years to your life, but adding life to your years.

Lisa Tamati
Functional Health Practitioner, Co-founder Aevum Labs, Host of Pushing the Limits Podcast