Ageing and the lymphatic system: implications for immunity, brain health, and possible therapeutic interventions

Apr 5, 2026Ageing research reviews

How Ageing Affects the Lymphatic System and Its Impact on Immunity, Brain Health, and Treatments

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Lymphatic vessel and immune organ decline with age is associated with impaired transport and chronic inflammation.

Age-related changes in the lymphatic system may disrupt immune cell movement and fluid balance.
Chronic low-grade inflammation linked to lymphatic dysfunction is increasingly associated with cardiovascular disease and metabolic issues.
In the brain, deterioration of lymphatic systems may impair the clearance of harmful substances, potentially accelerating cognitive decline.
Molecular mechanisms of lymphatic ageing include changes in cell junctions, stiffening of surrounding tissue, and altered signaling pathways.
Current gaps in research include the role of lymphatic changes as primary drivers of disease and limitations in existing animal models.

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The lymphatic system is essential for maintaining interstitial fluid balance, supporting immune surveillance, and clearing metabolic waste, yet its role in ageing has only recently come into focus. With age, lymphatic vessels and lymphoid organs undergo structural and functional decline, leading to impaired transport, disrupted immune cell trafficking, and chronic low-grade inflammation. These changes contribute to systemic inflammaging and are increasingly implicated in cardiovascular disease, metabolic dysfunction, and neurodegenerative disorders. In the central nervous system, deterioration of the glymphatic and meningeal lymphatic systems compromises cerebrospinal fluid circulation and the clearance of amyloid-β, tau, and other metabolites, thereby accelerating cognitive decline. In this review, we examine the molecular and cellular mechanisms that underline lymphatic ageing, including junctional remodeling, extracellular matrix stiffening, altered lymphangiogenic signaling, and endothelial senescence. We critically assess the consequences of lymphatic dysfunction for systemic and brain health, highlighting unresolved controversies such as the extent to which lymphatic changes are primary drivers of pathology, the limitations of rodent models and indirect imaging readouts, and the lack of ageing-resolved single-cell maps in human tissues. Finally, we discuss therapeutic avenues ranging from antioxidant and pro-lymphangiogenic strategies to lifestyle interventions and reconstructive microsurgery. Together these insights position the lymphatic system as a central, yet underexplored, determinant of resilience in ageing and a promising target for future gerotherapeutic interventions.

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Ageing and the lymphatic system: implications for immunity, brain health, and possible therapeutic interventions

Abstract

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