Highly protective immune cells in centenarians protect against illnesses

Centenarians have unique changes in their immune cell genomes, which may explain their longevity, according to new research.

People who live to 100 years or more are extremely rare, comprising less than one percent of the population. These individuals also experience a delay in age-related diseases. Researchers at Boston University and Tufts University School of Medicine, Massachusetts, hypothesised this could be due to a high-functioning immune system, which for most people deteriorates with age. To investigate, they performed a genomic technique called single-cell sequencing on immune cells from centenarians.

'The immune profiles that we observed in the centenarians confirms a long history of exposure to infections and capacity to recover from them,' summarised senior author Professor Paola Sebastiani, a multidisciplinary biostatistician from Tufts University School of Medicine.

She explained that their findings show centenarians are 'enriched for protective factors that increase their ability to recover from infections.'

Published in eBioMedicine, part of the Lancet, the team conducted single-cell sequencing on circulating immune cells from the blood of seven centenarians, who had a mean age of 106. Researchers then integrated the immune profiles of the subjects with previously published genomic data, generating a dataset from 66 individuals ranging from 20 to 119 years old. They found changes not only in the composition but also in the genetic signature of the immune cells from centenarians.

As expected, older participants (including those over 100 years of age) showed a lower proportion of B cells and T cells compared with younger subjects. The study also confirmed that the proportion of 'cytotoxic' cell types – immune cells with the capacity to kill infected or damaged cells – increases with age. However, the study unveiled unique findings specific to centenarians which have not previously been reported.

Namely, the authors identified 25 genes which showed significant changes in expression across age groups. Of these, several genes were only expressed in immune cells from subjects over the age of 100, including genes that are known inducers of immune response pathways that help to fight infection. In contrast, some genes which have previously been linked to ageing were significantly downregulated in centenarians compared with younger age groups.

Whether these changes in the immune system are a by-product of extreme ageing, or if they are in fact driving the participants' exceptional longevity, remains unresolved. However, the authors are hopeful that with further research, they can capitalise on their findings to devise healthy ageing therapeutics.

Senior author Dr George Murphy, from Boston University School of Medicine, said: 'Centenarians, and their exceptional longevity, provide a "blueprint" for how we might live more productive, healthful lives. We hope to continue to learn everything we can about resilience against disease and the extension of one's healthspan.'