Centenarians are a group of individuals exhibiting extreme longevity, who are characterized by a remarkable compression of morbidity. Therefore, centenarians have been postulated as a model of healthy aging. Different approaches have been used to decipher the biology and genetics of centenarians in order to identify key anti-aging pathways. The majority of studies have taken advantage of blood samples to perform their analysis. Besides, a recent study in human brain samples deciphered the transcription factor REST (Repressor Element-1 Silencing Transcription Factor) as an important player of extreme longevity and cognitive activity. This study goes from human to animal models and revealed that REST acts as an epigenetic regulator of neuronal homeostasis, to control aging and longevity. The aim of this view point is to summarize recent literature describing genetic and epigenetic factors, as well as molecular pathways associated with centenarians and the biology of aging. We will pay particular attention to the impact of REST in centenarians and longevity.
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