The secret to healthy ageing: clues from the immune system of centenarians 

Understanding why some people reach the age of 100 with remarkable functional capacity and greater resistance to age-related diseases, including cancer, is one of the major questions facing biomedical science today.

A new science review, published last week (April 24) in Nature Reviews Immunology, examines why many centenarians – people who live to 100 years old – retain a functional immune system and greater resistance to age-related diseases.

The international study involving researchers from Universidad Europea suggests that many centenarians retain immune characteristics typical of much younger people.

Professor at the Faculty of Medicine, Health and Sport at Universidad Europea, Alejandro Lucía, said:

“The immune systems of many centenarians display characteristics that help explain not only their longer lifespan, but also their greater resistance to age-related diseases.”

Professor Lucía is funded by Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme. In his view, the reviewed evidence suggests that “extreme longevity is not due to a single mechanism, but rather to a coordinated adaptation of the body that allows key immune functions to be preserved for longer”.

Preserving immune function

The study reviews the available scientific evidence on the immune system of centenarians. Despite their advanced age, many of them show relatively well-preserved immune function and greater resistance to processes linked to immune system ageing and low-grade chronic inflammation. These characteristics are even more pronounced in semi-supercentenarians (people aged 105-109 years old) and supercentenarians (people who reach 110 years old), whose immune profiles may resemble, in some respects, those of much younger adults.

The research team highlights that a review of international studies indicate that cancer incidence and mortality reduce markedly after 90 years old, with rates falling to 0-4% in people over 100.

Among the most significant findings, Professor Lucía’s review highlights reduced activation of inflammatory mechanisms linked to disease development, enhanced cellular recycling, and DNA signatures consistent with better preservation of immune function. It also points to improved immune surveillance, better-preserved gut microbial diversity, and gene expression patterns in circulating immune cells reminiscent of those in younger individuals.

Overall, the findings reinforce the idea that extreme longevity does not depend on a single factor, but rather on a coordinated adaptation of the body that enables it to maintain immune balance and greater resistance to disease.

World Cancer Research Fund International Executive Director of Research and Policy, Dr Giota Mitrou said:

“This unique review paper is providing much needed insight into the immune system of centenarians, particularly as this demographic continues to grow. Cancer is often considered a disease of ageing, but evidence from this population suggests that it does not increase indefinitely, and that cancer incidence begins to decline at a certain age.

Keeping the immune system balanced may be important for helping it work properly and avoid long-term inflammation. More research is needed to better understand how immune function could help improve health as people get older.”

The study highlights that significant questions remain in this novel area of research, such as the need to expand longitudinal studies and to better understand what occurs at the tissue and organ level, beyond the analyses carried out on blood circulating the body.