Does the trained immune system play an important role in the extreme longevity that is seen in the Sardinian blue zone?

Abstract

Villages in the island of Sardinia in the Mediterranean that display exceptional longevity are clustered within a defined mountainous region. Because of their unique location we hypothesize that these villages had a unique infectious disease exposure relevant to the observed successful longevity. These highland villages had a significant exposure to malaria in the first half of the 20th century after which malaria was eliminated due to vector control mechanisms. In addition, there is likely a high incidence of Helicobacter pylori infections among shepherds in Sardinia, the primary occupation of many living in the LBZ, as well as helminth infections among children. This suggests that individuals living in the LBZ had a unique infectious disease exposure. Specifically, we hypothesize that the continued high exposure of residents in the LBZ to these infectious agents prior to the 1950s lead to the generation of a uniquely trained (or imprinted) immune system. Once some of these diseases were eliminated in the latter half of the century, individuals within the LBZ were equipped with a trained immune system that was uniquely capable of not only responding effectively to common infections but also responding in a manner that maximized maintaining tissue health. In addition, there are lifestyle factors that also favor such a trained immune system. This hypothesis may help explain the slow progression of chronic immune mediated diseases as well as other chronic non-transmissible age-related diseases seen in the Sardinian LBZ and serve as a template for future studies that support or refute this hypothesis.

Helicobacter pylori Infection does not Protect Against Allergic Diseases: Evidence from a Pediatric Cohort in Northern Sardinia, Italy

“…Some molecular aspects of the H. pylori-host interaction may help explain our results. Unlike other microorganisms, the bacterium does not favor the proper maturation of the immune system but, on the contrary, induces a tolerogenic phenotype in the dendritic cells, able to facilitate the persistence of the infection [55]. These tolerogenic cells, through interleukin-10 release, could inhibit the development of effector T cells, thereby creating an imbalance that induces later the appearance of exaggerated responses in the host [56].…”

Helicobacter pylori infection in humans and phytotherapy, probiotics, and emerging therapeutic interventions: a review

“…H. pylori is a pathogen that can infect both humans and animals (Duan et al, 2023). In the Tatra Mountains of Poland, the prevalence of H. pylori was particularly high among shepherds and their family members (97.6% and 86%, respectively), compared with 65.1% among farmers who were not exposed to sheep (Papież et al, 2003;Soloski et al, 2022). In addition, H. pylori has been detected in milk, meat (mutton, beef) and other fresh foods, suggesting that milk and sheep milk may be a vector for H. pylori infection in humans (Hemmatinezhad et al, 2016;Shaaban et al, 2023).…”

Worms on stage

“…6 Immunologically, this has been linked to their induction of Th2like regulatory responses. In children, helminth exposure has been proposed to have protective effects in unique isolated settings 7 and intestinal nematodes led to decreases in markers of intestinal inflammation in some studies. 8 However, due to the risk of heavier parasite burdens and other associated comorbidities, disease-specific preventative strategies in children will likely favor probiotic interventions rather than helminth infection by intention.…”