Centenarians and the Secret of a Youthful Immune System: Nat Rev Immun | May 2026

Introduction

Ageing is typically associated with declining immune function (immunosenescence) and chronic low-grade inflammation (inflammageing), leading to increased susceptibility to infections, cancer, and metabolic diseases. However, centenarians—individuals aged 100 years or more—represent a unique population that defies this paradigm by maintaining relatively preserved immune function and delaying major age-related diseases.

Problem Statement

The key question is:

Why do centenarians escape the typical trajectory of immune decline seen in ageing?

Understanding the mechanisms behind their preserved immunity could unlock strategies to improve healthspan and prevent age-related diseases in the general population.

Summary

This review highlights that centenarians maintain a balanced and resilient immune system across both innate and adaptive compartments. Unlike typical ageing, they demonstrate reduced chronic inflammation, partly due to lower activation of inflammatory pathways such as the NLRP3 inflammasome and a more controlled senescence-associated secretory phenotype.

Protective mechanisms include enhanced autophagy, which helps clear damaged cellular components, and preservation of immune cell function resembling that of younger individuals. Omics studies reveal youth-like gene expression patterns, favourable epigenetic profiles, and beneficial gut microbiome composition, all contributing to immune stability.

Interestingly, semi-supercentenarians and supercentenarians show even stronger preservation of these features, suggesting that successful ageing involves active biological adaptation rather than passive decline.

Overall, centenarians achieve longevity through immune homeostasis, reduced inflammageing, and coordinated molecular adaptations, offering a potential blueprint for therapies aimed at extending healthy lifespan.