The demographic and social changes of the past decades have determined improvements in public health and
longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their
attention on centenarians as optimal model to address the biological mechanisms of “successful and unsuccessful
ageing”. They are equipped to reach the extreme limits of human life span and, most importantly, to show
relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such
as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background
and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based
on results obtained, we suggest longevity as the result of an optimal performance of immune system and an overexpression
of anti-inflammatory sequence variants of immune/inflammatory genes. However, as well known,
genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity.
Epigenetics is associated with ageing, as demonstrated in many studies. In particular, ageing is associated with a
global loss of methylation state. Thus, the aim of future studies will be to analyze the weight of epigenetic
changes in ageing and longevity