Limone sul Garda, a quaint location with less than one thousand inhabitants on the western side of Lake Garda, is famous all over the world for the presence of a beneficial protein that eliminates cholesterol in the blood of some of its inhabitants: it is a true “elixir of long life”. The small town, surrounded by between mountains and the lake used to be isolated from the rest of the world. This isolation and a series of fortuitous coincidences, allowed for the diffusion of the protein in the village. The discovery of the protein took place in 1979 when an employee of the state railroads was hospitalised. He was born in Limone but had been living in Milan for over 20 years, The clinical results of the tests were astonishing: even though the values of the patient’s cholesterol and triglycerides were very high, there weren’t considerable signs or serious damage to the arteries and heart. The doctors decided proceed with further examinations and they discovered an anomalous protein in the patient’s blood. They called it: Apolipoproteina A-1 Milano, because of where it was discovered. The researchers discovered the same strange protein in the blood of the patient’s father and daughter. The protein A-1 Milano behaves in an anomalous but beneficial way. It quickly removes fat from the arteries and takes it to the liver where it is ultimately eliminated. The discovered protein A-1 Milano is an extremely effective measure against arteriosclerosis and heart attack. The challenge for the researchers became to reveal why the genetic mutation took place only in Limone and to discover the influence of hereditary and climatic factors in its diffusion. All the inhabitants of the village had their blood tested. The results were very interesting and showed that a great number of residents were carriers of the gene. The next step was the reconstruction of the genealogical tree of the carriers through a careful investigation in the communal and parochial archives. All the carriers were descendants of a couple who married in the first half of the 17th century (1644), the date of the possible appearance of the protein. The diffusion of the gene was due to the numerous marriages between kinsmen, which characterized the history of the village until 1932 when the Gardesana road was built. The beautiful road characterised by the long tunnels dug into the mountains on the lake shore, interrupted the long period of isolation and opened the village up to the world. Thanks to the precious collaboration of all of Limone’s inhabitants, who accepted to have many blood tests taken, the researchers in the following years were able to synthesize the A1-Milano. They managed to transfer the capability to reproduce the protein in some bacteria. In the early nineties the researchers injected the cloned protein into animals. They obtained exceptional results for decreasing plaques in coronary arteries. In November 2003, the news that a team led by Steven Nissen reproduced the protein in an experimental drug finally arrived from the United States. The drug has been given to 47 heart disease patients for six weeks and the results have been surprising.

The plaque volume reduced by an average of 4,2%. It could be the most important discovery of the decade and people of Limone are proud that “the elixir of long life” started from their small village on the shore of Lake Garda. The Nissen synthesis of the protein should lead to a revolutionary drug for the cure of the most serious cardiovascular pathologies (first cause of death in the world). This news brings Limone back to the centre of world attention, with the arrival of many journalists and television troupes which come to shoot in the narrow streets of the village in “search of the protein”. The world attention reached the highest degree in may 2004 with the 5th International Scientific Congress on Apolipoprotein. The most important researchers responsible for the development in treating cardiovascular diseases met in Limone.

The meeting was an occasion for discussing 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 a gift that nature has given to the lucky inhabitants of Limone. It is also thanks to the healthy Mediterranean diet (rich of fish from the lake, oil and local citrus) and to the favourable and unique climate. Limone is in fact the most northern place where citrus cultivation is possible. People here have a very long life expectancy. Today the inhabitants of Limone share these gifts with tourists, mainly from Germany, who spend their holidays in this quiet resort on Lake Garda, maybe without knowing how much they are taking care of their health.

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

This is a story 300 years old, a story which Limone’s residents are proud of because of it is fundamental to the cure of cardiovascular disease (the first cause of death in the world). It has been given special attention in the new Tourism Documentation Centre which was inaugurated in March 2011 in the former Town Hall. On 26th May 2007 the Bocconi University of Milan chose Limone as the site for holding the ninth annual convention of the Rodolfo Debenedetti Foundation on the theme “Health, Longevity and Productivity”. Limone was selected because of this magic elixir of long life in the blood of so many residents which is portrayed in the long life expectancy of its inhabitants.

In the meantime trials continued and the protein has again become the centre of attention in the world of cardiovascular medicine. In October 2012 the Carlo Sirtori Foundation of Milan organised an international scientific conference in Limone sul Garda called “Present status of HDL Therapy”. Thanks to the tests taken, on this occasion, new carriers of the protein were identified. The greatest world experts in this sector, who participated at the conference, discussed the current status of the HDL therapy and also announced that in a few years time innovative medicines deriving from Limone’s apolipoprotein will be put on the market.