Inflammaging as a Target for Healthy Ageing

Ben Dugan; Jessica Conway; Niharika A. Duggal


Age Ageing. 2023;52(2):afac328 

In This Article

Abstract and Introduction


Life expectancy has been on the rise for the past few decades, but healthy life expectancy has not kept pace, leading to a global burden of age-associated disorders. Advancing age is accompanied by a chronic increase in basal systemic inflammation, termed inflammaging, contributing towards an increased risk of developing chronic diseases in old age. This article reviews the recent literature to formulate hypotheses regarding how age-associated inflammaging plays a crucial role in driving chronic diseases and ill health in older adults. Here, we discuss how non-pharmacological intervention strategies (diet, nutraceutical supplements, phytochemicals, physical activity, microbiome-based therapies) targeting inflammaging restore health in older adults. We also consider alternative existing pharmacological interventions (Caloric restriction mimetics, p38 mitogen-activated protein kinase inhibitors) and explore novel targets (senolytics) aimed at combating inflammaging and optimising the ageing process to increase healthy lifespan.


Globally, the world's population is ageing.[1] Although this might seem like good news, we spend more years in poor health towards the end of life, which is being recognised as a significant challenge faced by the National Health Service and this has prompted the UK government to set a target of improving health span in older adults by adding 5 more years of independent living by 2035. Thus, developing an understanding of these underlying biogerontological processes is vital for maintaining good health by reducing the risk of multimorbidity in old age.

An inflammatory response is a fundamental host defence mechanism elicited to maintain tissue homeostasis in response to an infection, damage or injury, and is characterised by an upregulation of inflammatory activity that resolves in the elimination of the threat.[2] In contrast to acute inflammation that triggers the healing process, long-term exposure to inflammation can negatively impact health, leaving the body in a constant state of activation and increasing the risk of developing age-related pathologies. Physiological ageing is characterised by a chronic state of elevated sub-clinical levels of inflammatory markers including tumour necrosis factor α (TNFα), IL-6, IL-1β, C reactive protein (CRP), serum amyloid A and fibrinogen, termed inflammaging,[3] and has been identified as a hallmark of ageing.[4] Importantly, a recent study has created a metric for systemic inflammation (iAge), which can predict the ageing trajectory, and CXCL9 was identified as the most robust contributor to iAge.[5]

Furthermore, a few studies have reported an age-associated increase in circulating transforming growth factor β (TGFβ), IL-4 and IL-10, which could potentially serve as a compensatory mechanism to counterbalance inflammaging.[6,7] However, these findings have been contradicted by other reports of an age-associated decline in circulating levels of IL-10.[8] Furthermore, ageing is accompanied by progressive mitochondrial dysfunction that can elicit a response that is not confined to the cell but can spread to distal tissues by means of soluble mediators, termed mitokines.[9] A systemic increase in the levels of mitokines, such as growth differentiation factor (GDF15) and fibroblast growth factor (FGF21), occurs with advancing age and can be beneficial in playing a protective role against systemic inflammation, thus could be considered as part of an 'anti-inflammaging' process.[10,11]

In this review, we will explore the existing literature to develop a better understanding of inflammaging and its negative impact on the quality of life, discuss potential intervention strategies and identify novel targets to counteract inflammaging and bridge the gap between lifespan and health span.