Early life adversity: programming inflammation and immunosenescence through immunometabolic pathways?

Jonathan Turner*

*Corresponding author for this work

Research output: Contribution to journalMeeting Abstractpeer-review


Whatever form early life adversity (ELA) takes it has long-term health consequences, increasing the risk of many non-communicable diseases that share a significant immune component. In our EpiPath institutionalisation-adoption cohort there was no clear increase in circulating inflammatory markers, however, there was a clear increase in peripheral pro-inflammatory T-cells. Both Th and Tc cells were skewed towards a more activated and senescent state, with differences increasing as the differentiation state advanced from naïve through to terminally differentiated cells. NK cells were also more senescent and lost their cytotoxic capacity after ELA exposure. Overall, these data demonstrate a long-term shift in differentiation state and activation level toward a pro-inflammatory senescent phenotype that shares many aspects with the aged immune system. Concurrently, studies from the ALSPAC cohort have identified long-term changes in DNA methylation induced by ELA. Preliminary analysis suggests that epigenetic age, as measured by epigenetic clocks, is not associated with the immunophenotype, however, specific physiological processes identified through EWAS and gene ontology analyses explain the associations between ELA, the immunophenotype and the long-term health consequences. Several independent early life stressors converge on metabolic pathways in EWAS studies, particularly mitochondrial energy processes such as oxidative phosphorylation. As our knowledge of immunemetabolism grows, it is becoming clear that there is a natural progression of mitochondrial dysfunction with aging leading to this characteristic immunephenotype. It would appear that ELA acts as an accelerator for non-communicable diseases through inflammageing and immunosenescence, and this is most probably mediated through the epigenetic regulation of metabolic pathways.
Original languageEnglish
Article number106259
Issue numberSuppl.
Publication statusPublished - Jul 2023
Event52nd annual meeting of ISPNE - Chicago, United States
Duration: 8 Sept 202210 Sept 2022


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