Cargando…
Impact of demography and population dynamics on the genetic architecture of human longevity
The study of the genetics of longevity has been mainly addressed by GWASs that considered subjects from different populations to reach higher statistical power. The "price to pay" is that population-specific evolutionary histories and trade-offs were neglected in the investigation of gene-...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128422/ https://www.ncbi.nlm.nih.gov/pubmed/30089705 http://dx.doi.org/10.18632/aging.101515 |
_version_ | 1783353638189531136 |
---|---|
author | Giuliani, Cristina Sazzini, Marco Pirazzini, Chiara Bacalini, Maria Giulia Marasco, Elena Ruscone, Guido Alberto Gnecchi Fang, Fang Sarno, Stefania Gentilini, Davide Di Blasio, Anna Maria Crocco, Paolina Passarino, Giuseppe Mari, Daniela Monti, Daniela Nacmias, Benedetta Sorbi, Sandro Salvarani, Carlo Catanoso, Mariagrazia Pettener, Davide Luiselli, Donata Ukraintseva, Svetlana Yashin, Anatoliy Franceschi, Claudio Garagnani, Paolo |
author_facet | Giuliani, Cristina Sazzini, Marco Pirazzini, Chiara Bacalini, Maria Giulia Marasco, Elena Ruscone, Guido Alberto Gnecchi Fang, Fang Sarno, Stefania Gentilini, Davide Di Blasio, Anna Maria Crocco, Paolina Passarino, Giuseppe Mari, Daniela Monti, Daniela Nacmias, Benedetta Sorbi, Sandro Salvarani, Carlo Catanoso, Mariagrazia Pettener, Davide Luiselli, Donata Ukraintseva, Svetlana Yashin, Anatoliy Franceschi, Claudio Garagnani, Paolo |
author_sort | Giuliani, Cristina |
collection | PubMed |
description | The study of the genetics of longevity has been mainly addressed by GWASs that considered subjects from different populations to reach higher statistical power. The "price to pay" is that population-specific evolutionary histories and trade-offs were neglected in the investigation of gene-environment interactions. We propose a new “diachronic” approach that considers processes occurred at both evolutionary and lifespan timescales. We focused on a well-characterized population in terms of evolutionary history (i.e. Italians) and we generated genome-wide data for 333 centenarians from the peninsula and 773 geographically-matched healthy individuals. Obtained results showed that: (i) centenarian genomes are enriched for an ancestral component likely shaped by pre-Neolithic migrations; (ii) centenarians born in Northern Italy unexpectedly clustered with controls from Central/Southern Italy suggesting that Neolithic and Bronze Age gene flow did not favor longevity in this population; (iii) local past adaptive events in response to pathogens and targeting arachidonic acid metabolism became favorable for longevity; (iv) lifelong changes in the frequency of several alleles revealed pleiotropy and trade-off mechanisms crucial for longevity. Therefore, we propose that demographic history and ancient/recent population dynamics need to be properly considered to identify genes involved in longevity, which can differ in different temporal/spatial settings. |
format | Online Article Text |
id | pubmed-6128422 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-61284222018-09-10 Impact of demography and population dynamics on the genetic architecture of human longevity Giuliani, Cristina Sazzini, Marco Pirazzini, Chiara Bacalini, Maria Giulia Marasco, Elena Ruscone, Guido Alberto Gnecchi Fang, Fang Sarno, Stefania Gentilini, Davide Di Blasio, Anna Maria Crocco, Paolina Passarino, Giuseppe Mari, Daniela Monti, Daniela Nacmias, Benedetta Sorbi, Sandro Salvarani, Carlo Catanoso, Mariagrazia Pettener, Davide Luiselli, Donata Ukraintseva, Svetlana Yashin, Anatoliy Franceschi, Claudio Garagnani, Paolo Aging (Albany NY) Research Paper The study of the genetics of longevity has been mainly addressed by GWASs that considered subjects from different populations to reach higher statistical power. The "price to pay" is that population-specific evolutionary histories and trade-offs were neglected in the investigation of gene-environment interactions. We propose a new “diachronic” approach that considers processes occurred at both evolutionary and lifespan timescales. We focused on a well-characterized population in terms of evolutionary history (i.e. Italians) and we generated genome-wide data for 333 centenarians from the peninsula and 773 geographically-matched healthy individuals. Obtained results showed that: (i) centenarian genomes are enriched for an ancestral component likely shaped by pre-Neolithic migrations; (ii) centenarians born in Northern Italy unexpectedly clustered with controls from Central/Southern Italy suggesting that Neolithic and Bronze Age gene flow did not favor longevity in this population; (iii) local past adaptive events in response to pathogens and targeting arachidonic acid metabolism became favorable for longevity; (iv) lifelong changes in the frequency of several alleles revealed pleiotropy and trade-off mechanisms crucial for longevity. Therefore, we propose that demographic history and ancient/recent population dynamics need to be properly considered to identify genes involved in longevity, which can differ in different temporal/spatial settings. Impact Journals 2018-08-08 /pmc/articles/PMC6128422/ /pubmed/30089705 http://dx.doi.org/10.18632/aging.101515 Text en Copyright © 2018 Giuliani et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Giuliani, Cristina Sazzini, Marco Pirazzini, Chiara Bacalini, Maria Giulia Marasco, Elena Ruscone, Guido Alberto Gnecchi Fang, Fang Sarno, Stefania Gentilini, Davide Di Blasio, Anna Maria Crocco, Paolina Passarino, Giuseppe Mari, Daniela Monti, Daniela Nacmias, Benedetta Sorbi, Sandro Salvarani, Carlo Catanoso, Mariagrazia Pettener, Davide Luiselli, Donata Ukraintseva, Svetlana Yashin, Anatoliy Franceschi, Claudio Garagnani, Paolo Impact of demography and population dynamics on the genetic architecture of human longevity |
title | Impact of demography and population dynamics on the genetic architecture of human longevity |
title_full | Impact of demography and population dynamics on the genetic architecture of human longevity |
title_fullStr | Impact of demography and population dynamics on the genetic architecture of human longevity |
title_full_unstemmed | Impact of demography and population dynamics on the genetic architecture of human longevity |
title_short | Impact of demography and population dynamics on the genetic architecture of human longevity |
title_sort | impact of demography and population dynamics on the genetic architecture of human longevity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128422/ https://www.ncbi.nlm.nih.gov/pubmed/30089705 http://dx.doi.org/10.18632/aging.101515 |
work_keys_str_mv | AT giulianicristina impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT sazzinimarco impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT pirazzinichiara impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT bacalinimariagiulia impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT marascoelena impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT rusconeguidoalbertognecchi impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT fangfang impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT sarnostefania impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT gentilinidavide impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT diblasioannamaria impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT croccopaolina impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT passarinogiuseppe impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT maridaniela impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT montidaniela impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT nacmiasbenedetta impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT sorbisandro impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT salvaranicarlo impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT catanosomariagrazia impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT pettenerdavide impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT luisellidonata impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT ukraintsevasvetlana impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT yashinanatoliy impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT franceschiclaudio impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity AT garagnanipaolo impactofdemographyandpopulationdynamicsonthegeneticarchitectureofhumanlongevity |