Why inflammation quietly shifts after 40

Recovery takes a little longer. The joints that once shrugged off a long run or a difficult travel week now register the effort for days. Energy dips arrive earlier in the afternoon. Most people over 40 put this down to pace of life — but there is a quieter biological explanation running underneath all of it.

Researchers call it inflammaging: the chronic, sterile, low-grade inflammation that accumulates with age even in people who appear perfectly healthy. The term was coined by immunologist Claudio Franceschi, and in 2023 López-Otín and colleagues formally elevated it to a true Hallmark of Aging. Measurable levels of pro-inflammatory markers — IL-6, TNF-α, and C-reactive protein — rise reliably in healthy adults past 40, and elevated IL-6 in particular has been associated with disability and all-cause mortality in older populations.

The picture sharpens further for women in perimenopause: declining oestrogen removes one of the body's natural anti-inflammatory buffers, while a slowing metabolism makes the system less efficient at clearing inflammatory load. The compound effect is real, even when no single symptom feels alarming.

Here is the critical point: a 2025 study from Columbia University, published in Nature Aging, found that in non-industrialised populations inflammation simply did not rise with age — and chronic diseases such as heart disease, diabetes, and Alzheimer's were largely absent. Inflammaging, it turns out, appears to be a product of how people live, not an inescapable feature of growing older. That distinction matters, because it makes the next question a practical one: what, specifically, can you put on your plate to start shifting the signal?

The colour rule: what it is and why it works

Colour is not decoration on a plant — it is chemistry. The pigments that give blueberries their deep blue, tomatoes their red, and kale its dark green are not incidental; they are distinct phytochemical families, each operating through different anti-inflammatory mechanisms. Eating a narrow, beige palette means those mechanisms go largely unactivated.

Blues and purples — blueberries, blackberries, red cabbage — get their hue from anthocyanins, a class of flavonoids that may inhibit the signalling pathways responsible for releasing pro-inflammatory cytokines, including IL-6. The Arthritis Foundation specifically recommends blueberries, blackberries, and cherries for this reason.

Reds — tomatoes, watermelon, red peppers — are rich in lycopene, a fat-soluble antioxidant associated with reduced CRP in several observational studies. Because lycopene is fat-soluble, a drizzle of extra-virgin olive oil on roasted tomatoes is more than habit: it improves absorption meaningfully.

Oranges and yellows — sweet potato, carrots, turmeric — deliver carotenoids and, in turmeric's case, curcumin. Curcumin's multi-pathway activity (inhibiting NF-κB transcription, suppressing COX-2 and LOX enzymes, and activating the Nrf2 antioxidant defence system) has attracted considerable research interest. However, the evidence remains investigational: clinical readiness for specific conditions has not been established, and curcumin's bioavailability is inherently low without piperine — the compound found in black pepper — to aid absorption.

Greens — broccoli, spinach, kale — supply vitamin K, folate, and chlorophyll, each contributing to cellular repair processes and systemic inflammatory regulation through overlapping but distinct routes.

The practical upshot is that variety does the work that any single food cannot: every colour band activates a different part of the anti-inflammatory toolkit.

How to build the plate

The plate itself is straightforward once the proportions are fixed. Think of it in three zones, with fat as the fourth element that ties them together.

Half the plate: vegetables and fruit

Fill this zone with colour variety rather than volume of any single item — the colour logic already mapped in the previous section applies directly. The Arthritis Foundation sets a practical benchmark: aim for 2–3 cups of vegetables and 1.5–2 cups of fruit per meal. Spinach, kale, broccoli, peppers, and tomatoes are reliable anchors; the colours rotated through the week determine which anti-inflammatory pathways stay active.

A quarter: protein

Twice weekly, 3–4 oz of oily fish — salmon, mackerel, or sardines — delivers EPA and DHA, the omega-3 fatty acids that actively inhibit inflammatory signalling and help redress the omega-6-heavy balance many modern diets carry. On other days, eggs, legumes, tofu, or lean poultry fill the zone without adding the saturated-fat load that sustains the inflammatory cycle.

A quarter: complex carbohydrates

Sweet potato, quinoa, brown rice, and lentils release glucose slowly, avoiding the insulin spikes that drive systemic inflammation. Refined white carbohydrates do the opposite: replacing them with high-fibre alternatives is one of the most direct levers available at any meal.

The fat layer: extra-virgin olive oil

Use it generously. EVOO contains oleocanthal, a polyphenol with COX-inhibiting properties — though evidence for that specific compound remains at a research stage. What is well established is the practical benefit: fat-soluble carotenoids and lycopene require dietary fat to be absorbed properly, making EVOO a functional part of the plate rather than an optional garnish. A daily handful of walnuts, pine nuts, or almonds (around 1.5 oz) adds further monounsaturated fat alongside fibre and protein.

The British Heart Foundation notes that the strongest evidence for anti-inflammatory eating comes from whole-diet population studies rather than individual foods tested in isolation. Mediterranean and DASH patterns — built on exactly these proportions of vegetables, wholegrains, unsaturated oils, and fish — show the most consistent reductions in cardiovascular risk linked to inflammation. The template above is designed to mirror those patterns, meal by meal.

What works against the plate

Signals noise up the system just as reliably as good food quietens it — and several common dietary patterns actively sustain the inflammatory environment that the colour rule works to reduce.

Refined carbohydrates and sugary drinks act most directly. A spike in blood glucose triggers a corresponding surge in insulin, which upregulates the production of pro-inflammatory cytokines including IL-6 and TNF-α. The mechanism is not vague: it is a biochemical cascade that can be repeated multiple times a day with each refined-carb meal. Replacing white bread, white-flour pasta, and sweetened drinks with the high-fibre complex carbohydrates already outlined in the plate template is the single most direct lever available.

Omega-6 excess is a ratio problem rather than a toxin problem. Industrialised seed oils — sunflower, corn, soybean — crowd out EPA and DHA by competing for the same metabolic pathways; shifting that ratio by reducing seed oil use while adding oily fish or plant omega-3 sources (chia, flaxseed, walnuts) is mechanistically grounded.

Ultra-processed foods further erode the plate by displacing the polyphenol diversity that whole foods provide; some research also suggests additives common in ultra-processed products may affect intestinal integrity, though the evidence in that area is still developing.

Alcohol, even in moderate amounts, has been associated with elevated CRP and may disrupt the overnight repair window where much of the body's restorative chemistry occurs — worth factoring in as one design variable among several.

The framing here is deliberate: these are not forbidden categories but inputs that add noise to a system trying to run clean. Reducing them creates space for the anti-inflammatory signals to register.

The Chemistry pillar in 'Regeneration by Design'

Plates built around colour and proportions produce changes that show up in biomarkers. Inflammation — described within the Regen PhD framework as 'the primary driver of biological ageing and the most actionable system to monitor and shift' — leaves a measurable trail: hs-CRP, IL-6, and related markers rise quietly with age and may fall in response to sustained dietary changes. The Regen Blood Panel targets hs-CRP among 32 markers for exactly this reason: not as a starting point for dietary choices, but as a verification step once those choices are in place. Shift the Chemistry, then check whether it registered.

What lifts this beyond a nutrition protocol is pillar interdependence. Reduced systemic inflammation benefits joints and connective tissue directly — a Physics dividend for anyone managing load or recovery from physical training. It also creates conditions that Biology requires: gut health, immune regulation, and sleep quality all respond to the same polyphenol-rich inputs the colour rule provides. These are not parallel interventions but one system moving in the same direction.

Professor Paul Lee's Practical Regeneration, published in February 2026, develops these applied connections in full — the Chemistry decisions made at each meal feeding into Physics and Biology simultaneously. The colour rule is, in that context, one of the most accessible entry points into the framework set out in Regeneration by Design.

Three things to change at your next meal

Three changes. Not ten.

Tonight: look at the plate and identify which colour zone is missing. Most people default to green and orange — that leaves blues and purples (blueberries, red cabbage, beetroot) and reds (tomatoes, red pepper) chronically absent. Add one.

This week: swap one refined-carb component for its whole-food equivalent. White rice becomes brown rice or lentils. White bread becomes sourdough rye. One swap, sustained across the week, interrupts the insulin-spike cycle that s4 describes as the most direct biochemical driver of the inflammatory signal.

Also this week: schedule oily fish into two meals. Sardines on rye toast counts. Tinned salmon stirred through lentils counts. It does not need to be elaborate to deliver EPA and DHA.

If you track biomarkers: hs-CRP is the readout you're aiming to move. Give the dietary shift 8–12 weeks before revisiting a baseline — that is long enough for a sustained pattern to register.

This is general nutrition guidance, not a substitute for personalised medical advice; anyone managing a health condition should speak with a healthcare professional before making significant dietary changes. Beyond that, the work is specific and the feedback is measurable — which is exactly how a designed change ought to behave.

1. [1] Inflammaging. https://en.wikipedia.org/?curid=59830296 https://en.wikipedia.org/?curid=59830296