Which neutrophil metric is more informative?
| Metric | What it really tells you | When it can mis-lead |
|---|---|---|
| Absolute neutrophil count (ANC) | ||
| (cells × 10³/µL) | • Size of your myeloid “standing army.” | |
| • Correlates with bone-marrow output, innate immune capacity, and chronic low-grade inflammation (“inflammaging”). | Falls whenever total WBC falls (e.g., calorie restriction, some viral infections, myelosuppression) —so you must interpret it with context (CR, drugs, etc.). | |
| Percent neutrophils | • Fraction of total leukocytes that are neutrophils. | |
| • Useful for spotting acute shifts (e.g., a bacterial spike pushes %-neutrophils up even when total WBC stays normal). | Can look “normal” or “high” simply because lymphocytes have dropped (–> higher percentage even if neutrophils haven’t risen). |
Bottom line: For ageing biology, ANC (the raw count) plus the neutrophil-to-lymphocyte ratio (NLR) beats percentage alone.
Why ANC (and NLR) line up better with ageing phenotypes
- Myeloid skew & “inflammaging.”
- Ageing HSCs tilt toward myeloid lineages, so absolute neutrophil counts often creep upward even when lymphocytes fall. Higher ANC tracks with higher IL-6, CRP, and all-cause mortality in older cohorts.
- Predictive value in geriatrics.
- Large prospective studies (e.g., Rotterdam, UK Biobank) show that people in the highest ANC or NLR quintile have significantly higher risk of frailty, CVD, dementia, and mortality—even after adjusting for lifestyle and comorbidities.
- Calorie restriction (CR) nuance.
- CR lowers total WBC, usually by trimming both neutrophils and lymphocytes (and platelets). The drop in ANC under CR is not interpreted as immunosenescence; instead it reflects lower systemic inflammatory tone (less IL-6/G-CSF drive).
- In CR mice and in CALERIE-II humans, ANC fell ~15 % while innate responses to challenge remained intact.
- Percent neutrophils without the denominator misleads.
- In many elderly adults lymphocytes fall faster than neutrophils, so %-neutrophils may rise into “high-normal” territory even though ANC is flat or only modestly elevated. Conversely, a CR practitioner can have a low ANC but also a lower WBC, so %-neutrophils stays mid-range.
Practical take-aways
- Track ANC and lymphocyte count together; use them to compute NLR (ANC / absolute lymphocytes). NLR > 3–4 is consistently associated with worse biological-age phenotypes and higher mortality.
- If you practice moderate CR and see both ANC and lymphocytes down—but NLR unchanged or lower—that pattern aligns with reduced systemic inflammation, not immunosenescence.
- A rising ANC or rising NLR over time, especially with elevated CRP, ferritin, or IL-6, is a red flag for inflammaging and warrants a look at visceral adiposity, periodontal status, latent infection, or clonal hematopoiesis.
So, when talking about ageing and longevity, it’s the absolute numbers—and how neutrophils relate to the rest of the white-cell population—rather than the neutrophil percentage alone that carry the biologically relevant signal.
