title: Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring.
abstract: Given the dramatic increase in ageing populations, it is of great importance to understand the genetic and molecular determinants of healthy ageing and longevity. Semi-supercentenarians (subjects who reached an age of 105-109 years) arguably represent the gold standard of successful human ageing because they managed to avoid or postpone the onset of major age-related diseases. Relatively few studies have looked at epigenetic determinants of extreme longevity in humans. Here we test whether families with extreme longevity are epigenetically distinct from controls according to an epigenetic biomarker of ageing which is known as "epigenetic clock". We analyze the DNA methylation levels of peripheral blood mononuclear cells (PBMCs) from Italian families constituted of 82 semi-supercentenarians (mean age: 105.6 ± 1.6 years), 63 semi-supercentenarians' offspring (mean age: 71.8 ± 7.8 years), and 47 age-matched controls (mean age: 69.8 ± 7.2 years). We demonstrate that the offspring of semi-supercentenarians have a lower epigenetic age than age-matched controls (age difference=5.1 years, p=0.00043) and that centenarians are younger (8.6 years) than expected based on their chronological age. By contrast, no significant difference could be observed for estimated blood cell counts (such as naïve or exhausted cytotoxic T cells or helper T cells). Future studies will be needed to replicate these findings in different populations and to extend them to other tissues. Overall, our results suggest that epigenetic processes might play a role in extreme longevity and healthy human ageing.
authors.affiliation: Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.|Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, 40126 Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pirazzini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, 40126 Bologna, Italy.|Personal Genomics S.r.l., 37134 Verona, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Bacalini
authors.affiliation: Istituto Auxologico Italiano IRCCS, Cusano Milanino, 20095 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gentilini
authors.affiliation: Istituto Auxologico Italiano IRCCS, Cusano Milanino, 20095 Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Blasio
authors.affiliation: Personal Genomics S.r.l., 37134 Verona, Italy.|Functional Genomics Center, Department of Biotechnology, University of Verona, 37134 Verona, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Delledonne
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, 20122 Milan, Italy.|Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, 20122 Milan, Italy.|Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arosio
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50139 Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.affiliation: Department of Cell Biology, University of Calabria, 87036 Rende, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
authors.affiliation: Department of Cell Biology, University of Calabria, 87036 Rende, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Rango
authors.affiliation: Department of Cell Biology, University of Calabria, 87036 Rende, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: D'Aquila
authors.affiliation: Department of Biological, Geological and Environmental Sciences, Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, 40126 Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Giuliani
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, 40126 Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Marasco
authors.affiliation: Molecular Biomarkers, Nestlé Institute of Health Sciences SA, 1015 Lausanne, Switzerland.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Collino
authors.affiliation: Functional Genomics, Nestlé Institute of Health Sciences SA, 1015 Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, 40126 Bologna, Italy.|CRBA, Center for Applied Biomedical Research, St. Orsola-Malpighi University Hospital, 40138 Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Garagnani
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.|Interdepartmental Center "L. Galvani", University of Bologna, 40126 Bologna, Italy.|CNR, Institute of Organic Synthesis and Photoreactivity (ISOF), 40129 Bologna, Italy.|IRCCS, Institute of Neurological Sciences of Bologna, 40139 Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001683:Biological Clocks; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007558:Italy; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D008954:Models, Biological
keywords: DNA methylation; biomarker of ageing; epigenetic clock; semi-supercentenarians; semi-supercentenarians offspring