Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as ‘inflammageing’. In this Review article, we highlight how the processes of inflammation and senescence drive each other, leading to loss of immune function. To break this cycle, therapies are needed that target the interactions between the altered tissue environment and the immune system instead of targeting each component alone. We discuss the relative merits and drawbacks of therapies that are directed at eliminating senescent cells (senolytics) and those that inhibit inflammation (senomorphics) in the context of tissue niches. Furthermore, we discuss therapeutic strategies designed to directly boost immune cell function and improve immune surveillance in tissue

Biological sex is a crucial, but poorly understood variable in age-related susceptibility to infections and chronic inflammation, inflammageing. Monocytes are important immune cells responsible for in...

Centenarians — individuals aged 100 years or older — constitute a biologically distinct human population that achieves exceptional longevity while frequently retaining functional independence and avoiding major age-related diseases or postponing their onset. Despite their advanced age, many centenarians show relatively preserved immune function and resistance to conditions linked to immunosenescence and chronic low-grade inflammation (inflammageing). These features are especially pronounced in semi-supercentenarians (105–109 years) and supercentenarians (≥110 years), whose immune profiles often resemble those of much younger individuals. In this Review, we explore how centenarians modulate key hallmarks of immune ageing across innate and adaptive immune compartments. We discuss evidence that they limit the pathological effects of inflammageing, potentially through reduced NLRP3 inflammasome activation, enhanced autophagy and a tempered senescence-associated secretory phenotyp

Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as ‘inflammageing’. In this Review article, we highlight how the processes of inflammation and senescence drive each other, leading to loss of immune function. To break this cycle, therapies are needed that target the interactions between the altered tissue environment and the immune system instead of targeting each component alone. We discuss the relative merits and drawbacks of therapies that are directed at eliminating senescent cells (senolytics) and those that inhibit inflammation (senomorphics) in the context of tissue niches. Furthermore, we discuss therapeutic strategies designed to directly boost immune cell function and improve immune surveillance in tissue

Nature Reviews Immunology, Published online: 23 April 2026; doi:10.1038/s41577-026-01291-5What is unique about the immune system of people who live to extreme old age? Here the authors describe that centenarians may achieve such longevity through several mechanisms, including limiting the pathological effects of inflammageing and immunosenescence, preservation of immune surveillance, sustained gut microbial diversity and maintenance of intestinal barrier integrity.

Nature Reviews Immunology, Published online: 23 April 2026; doi:10.1038/s41577-026-01291-5What is unique about the immune system of people who live to extreme old age? Here the authors describe that centenarians may achieve such longevity through several mechanisms, including limiting the pathological effects of inflammageing and immunosenescence, preservation of immune surveillance, sustained gut microbial diversity and maintenance of intestinal barrier integrity.

ContentsAbout the JournalEditorial PoliciesSubmissionThird-Party PermissionsManuscript Preparation: Format, Structure, and Style

Background: Immune function alters with age, and is often accompanied by chronic, low-grade inflammation (inflammageing). In individuals with frailty, inflammageing is increased, reducing immune funct...

Chronic low-grade inflammation, termed “inflammageing”, accelerates many age-related diseases. C-reactive protein (CRP) is a well-validated biomarker of inflammation and is an independent predictor of...

Nature Reviews Molecular Cell Biology, Published online: 06 January 2026; doi:10.1038/s41580-025-00936-yClonal haematopoiesis of indeterminate potential (CHIP) is an ageing-related condition associated with a substantial fraction of leukocytes descending from a single somatically mutated haematopoietic stem cell. This Review discusses the molecular and cellular mechanisms that cause CHIP, its interplay with inflammageing, and the pathophysiological consequences and translational implications for older individuals.

Nature Reviews Molecular Cell Biology, Published online: 06 January 2026; doi:10.1038/s41580-025-00936-yClonal haematopoiesis of indeterminate potential (CHIP) is an ageing-related condition associated with a substantial fraction of leukocytes descending from a single somatically mutated haematopoietic stem cell. This Review discusses the molecular and cellular mechanisms that cause CHIP, its interplay with inflammageing, and the pathophysiological consequences and translational implications for older individuals.

In this study we have combined RNAseq with functional experiments to describe the phenotype of neutrophils from people with frailty. We found that frailty