Think of these ordinary experiences: a sore throat, a sunburn, and the aching legs two days after your first marathon (delayed onset muscle soreness, or DOMS). These are effects of inflammation (acute) and your body is just doing its job.

These experiences share a shape. Pain and swelling rise, peak within a day or two, and fade. DOMS, for example, typically peaks around day two and is gone in about a week or so.

This shape is what makes acute inflammation useful: a short-term, helpful reaction to injury or infection that starts, does its work and stops.

Chronic inflammation is what happens when the stopping part fails. It is a prolonged, low-grade immune response that lasts for extended periods and quietly damages healthy cells, tissues and organs.

A single point on the curve cannot tell the two apart. A blood marker, CRP, that is high today could be the rising edge of a sprain, or part of a flat line that has been there for years.

"Is your CRP high today?" and "Is your CRP persistently drifting up?" are different questions. The second is about chronic inflammation, and only repeated measurement can answer it.

Why it matters: three long-term risks

Chronic inflammation is not a disease on its own. It is a background condition that is linked to the diseases that most shape how long, and how well, people live (healthy). Some of the common ailments:

1. Cardiovascular disease

2. Type 2 diabetes and insulin resistance

3. Neurodegenerative disorders

   
   

Inflammation can be a driver, a passenger or both, depending on the disease and the person. What makes it a useful target for measurement is that it sits upstream of several conditions at once, and that markers of it can be measured in blood.

How we measure inflammation today

Inflammation is one of the few ageing-related processes you can read from an ordinary blood draw. Three tests do most of the work:

CRP and hs-CRP are often described as two markers: they are one molecule. hs-CRP is simply the assay that works at the low end.

All three share the same limitation. Each is a snapshot, and each is non-specific. A cold, a hard training week, a vaccination, an injury or a bad night's sleep can all move them. Clinical practice already reflects this: an hs-CRP taken during an acute illness is generally not interpreted, and clinicians repeat it after recovery and a standard blood test for an athlete is preferred after at least 24 hours of rest period.

That habit of repeating the test is the point. The medical system already knows a single reading is not enough.

The Hallmarks of Aging, in brief

Hallmarks of Aging is a framework most ageing researchers use to organise the field: introduced by Carlos López-Otín and colleagues in Cell. The 2013 paper proposed nine hallmarks. A 2023 update (López-Otín et al., Cell 186:243–278) expanded the list to twelve, adding disabled macroautophagy, chronic inflammation and dysbiosis.

A proposed hallmark has to meet three criteria: it appears during normal ageing; experimentally worsening it accelerates ageing; and experimentally improving it slows ageing or extends healthy lifespan.

The twelve are grouped into three tiers, from initial cause to downstream consequence:

Chronic inflammation sits in the integrative tier. In the paper's words, integrative hallmarks arise when the damage from the primary and antagonistic hallmarks "cannot be compensated any more", and together they "dictate the pace of aging". Inflammation is not where ageing starts. It is where accumulated damage becomes a system-wide problem.

What the 2023 paper says about inflammation

The review makes four points that matter, in my opinion, for anyone building measurement around inflammation.

Inflammation rises with age, and you can see it in blood. The paper calls this "inflammaging" and notes that circulating inflammatory cytokines and biomarkers, CRP among them, increase with ageing.

It is a hallmark in its own right. Although systemic inflammation is linked to all the other alterations, the authors write that it "constitutes a hallmark on its own", because manipulating the inflammatory and immune system can speed up or slow down ageing across organ systems.

It is the end of a long chain. Inflammaging, they explain, results from derangements that stem from all the other hallmarks: DNA leaking into the cell's cytoplasm, senescent cells releasing inflammatory signals, clonal changes in blood stem cells, and immune cells that wear out.

Time and rhythm are part of the mechanism. The paper states that inflammaging is also exacerbated by perturbations of circadian rhythms and by intestinal barrier dysfunction. Hold on to that sentence. It comes back in the section on the hallmarks of health.

The other half of the picture: hallmarks of health

The hallmarks of ageing describe what goes wrong. The same paper also points to a second framework, the hallmarks of health, which describes what the body loses as a result. The authors, in earlier work, proposed eight, in three groups:

Here is what I find useful about them. Four of the eight describe how the body behaves over time or after a challenge:

• Rhythmic oscillations. Loss shows as de-synchronisation of daily and longer biological rhythms. A pattern across days cannot be read from one point.

• Homeostatic resilience. The ability to return to baseline after a perturbation. It needs a before and an after.

• Hormetic regulation. Responding adaptively to low-dose stress, such as exercise. It shows in how the response changes with dose and repetition.

• Repair and regeneration. Time-to-recovery and in whether recovery is complete.

The grouping of these four as time-dependent is my reading of the framework, not the authors' claim. But it connects directly back to the earlier point: the same paper says circadian disruption exacerbates inflammaging. Inflammation is not only a level. It is entangled with timing, rhythm and recovery.

What a health trajectory looks like

If chronic is a statement about time, what would a health trajectory need? To me, this has five parts.

1. Inputs. Serial hs-CRP, plus routine-panel markers such as albumin, white cell and lymphocyte counts (and the neutrophil-lymphocyte ratio derived from them). Metabolic companions like glucose and lipids add context. These are tests people already take, so the data is cheap to collect and clinically familiar.

2. Context events. Illness, vaccination, injury, travel, stress, training load and sleep (quality and quantity). These let the system explain a spike instead of alarming on it. A raised hs-CRP the week after a flu shot is not the same finding as one that appears in three consecutive quiet months.

3. Wearable signals. Resting heart rate, heart-rate variability and sleep, used as between-test proxies. They also bring rhythm and recovery into view, which connects back to the hallmarks of health.

4. Outputs. A personal baseline; the slope of the trend; a persistence flag, meaning elevation across several draws with no acute explanation; recovery after a logged perturbation; and intervention response, for example the CRP trend before and after a 12-week programme (indicative) for hormonal health management or rheumatoid arthritis.

5. Action. A clinician review queue. The clinical platform should surface patterns, and thresholds are set by medical advisors. It supports clinical judgment and does not diagnose.

Mapped back to the four hallmarks of health, the design is deliberately modest. Wearable rhythms speak to rhythmic oscillations. Time-to-baseline after a logged event speaks to homeostatic resilience and to repair. The response to exercise or a structured programme speaks to hormetic regulation. Each mapping is a hypothesis to test, not an established clinical metric.

What I am confident of is the narrower point. Chronic inflammation is defined by time, a single blood test is a single point in time, and a health system that wants to see chronic processes has to learn to read lines instead of dots.

This is not a new instinct. In From Lifespan to Healthspan (Part 1, Part 2), our medical advisor, Dr. Krishnamurthy, shows that ageing is measurable, and what has the strongest evidence for extending healthy years. Part 2 also describes phenotypic flexibility: how fully the body’s metabolism and inflammation return to baseline after a standard meal. That is a trajectory measured over a few hours.

The open question is what the same view looks like over months or years, in everyday life. That is the gap we are building OHUE-SIRA to close. A trajectory tells a clinician when to look, not what to do.

Sources

• López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell 186:243–278 (2023).

• López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 153:1194–1217 (2013).

• CIHW, From Lifespan to Healthspan, Part 1 and Part 2.