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Limone sul Garda, a nice resort with less than one thousand inhabitants on the western river of Garda lake, is famous all over the world for the presence in the blood of some of its inhabitants of a beneficial protein that eliminates cholesterol: a true “elixir of long life”.

The small town, enclosedbetween mountains and the lake, was isolated in the past from the rest of the world. Thanks to this isolation, both with a series of lucky and fortuitous coincidences, the protein could spread abroad in the village.

The history of the discovery begin in 1979 when an employee of the state railroads, born in Limone, but who has been living in Milan for over 20 years, was hospitalised for a check-up.

The clinical results were astonishing: even if the values of the patient’s cholesterol and triglycerides were very high, there weren’t considerable clinical signs or serious damage to arteries andheart. The doctors decided for a thorough examination and they discovered in the patient’s blood an anomalous protein that they called Apolipoproteina A-1 Milano (the town of the discovery). The researchers discovered the same strange protein in the blood of the patient’s father and daughter. The protein A-1 Milano behave in anomalous but beneficial way, quickly removingfat from arteries and leading it to the lever which in the end eliminates it. The discovered protein A-1 Milano is an extremely effective measure against arteriosclerosis and heart attacks. The challenge for the researchers became to reveal why the genetic mutation took place only in Limone and the influence of hereditary and climatic factors in its spread. All the inhabitants of the village have been examined by blood tests. The results were very interesting: a great number of residents were carriers of that gene.

The next step has been the reconstruction of the genealogical tree of the carriers through a careful investigation in the communal and parochial archives; all carriers were descendants of a couple who married in the first half of the XVII century (1644), date of the possible appearance of the protein. The spread of the gene was likely due to the numerous marriages between kinsmen, that have characterized the history of the country till 1932 when the building of the Gardesana, a beautiful road with long galleries dug in the deep cliff of the mountains near the lake, interrupted the millenary isolation, opening the village to the world.

Thanks to the precious collaboration of all Limone inhabitants, who accepted to have many blood tests, the researchers in the following years could try to synthesize the A1-Milano, transferring in some bacteria the capability to reproduce the protein. In the first nineties the researchers injected the cloned protein into animals getting exceptional results in the decrease of plaques in coronary arteries. In November 2003, finally arrived from the United States the news that a team led by Steven Nissen has reproduced the protein in an experimental drug. The drug has been given to 47 heart disease patients for six weeks and the results have been surprising: the plaques’ volume reduced by an average of 4,2%. It could be the most important discover of the decennium and people of Limone are proud that “the elixir of long life” started from their small village on the river of Garda lake.

The Nissen synthesis of the protein shall lead to a revolutionary drug for the cure of the most serious cardiovascular pathologies (first reason of death in the world). This news bring back Limone to the centre of world attention,with so many journalists and television troupes which come to shoot in the narrow streets of the old village at “the search of the protein”. The world attention reached the highest degree in the last may with the 5Th International Scientific Congress on Apolipoprotein, when the most important researchers responsible for the development in treating cardiovascular diseases met in Limone.

The meeting has been an occasion for discussing about medical issues but also for speaking about the peculiar longevity of the inhabitants of Limone, where a high percentage is over 80.

The protein is not the only gift given to the lucky inhabitants by Nature because, thanks to the healthy Mediterranean diet (rich of fish of lake, oil and local citrus) and to the favourable and unique climatic conditions (Limone is actually the most northern place where citrus cultivation is possible), they have a very long life expectation. Today the inhabitants of Limone share these gifts with tourists, mainly from Germany, who spend their holidays in this quiet resort on the Garda Lake, maybe without knowing how much they are taking care of their health.

In 2004 the medical equipe of Sirtori came back in Limone and researchers effected blood tests on the new-born children of carriers. They discovered that the number of the carriers of the precious protein A1-Milano was increased. Eight children have joined the group of about 40 carriers, so the history of “elixir of long life”, born fortuitously centuries ago thanks to the geographic isolation of the village, can go on.