Abstract
Human longevity is a complex trait in which genetics, epigenetics, environmental and stochasticity differently contribute. To disentangle the complexity, our studies on genetics of longevity were, at the beginning, mainly focused on the extreme phenotypes, i.e. centenarians who escaped the major age-related diseases compared with cross sectional cohorts. Recently, we implemented this model by studying centenarians’ offspring and offspring of non-long lived parents. In association, during studies on many candidate genes SNPs, positively or negatively correlated with longevity have been identified. The results obtained on Insulin-like Growth Factor 1 Receptor (IGF1R) polymorphisms showed a correlation between specific genetic variants combinations and the low plasma level of IGF1 in centenarians, suggesting an impact of the IGF-I/insulin pathway on human longevity. This pathway together with mammalian target of rapamycin (mTOR) will be reviewed as being the most promising for longevity. Further, we will summarise the role of apolipoprotein E (APOE) variants in human longevity since the results of the large European project GEHA (Genetics of Healthy Aging) indicate APOE among the chromosomal loci associated with longevity. On the other hand, the identification of longevity-related genes does not explain the mechanisms of healthy aging and longevity rather pose questions on epigenetic contribution, gene regulation and the interactions with essential genomes, i.e. mitochondrial DNA and microbiota. To fully disentangle what appears to be an endless quest, all the components of the complexity of human longevity genetics are taken into account.
| Original language | English |
|---|---|
| Pages (from-to) | 707-717 |
| Number of pages | 11 |
| Journal | Current Vascular Pharmacology |
| Volume | 12 |
| Issue number | 5 |
| Publication status | Published - 2014 |
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Keywords
- APOE
- ELOVL2
- Epigenetics
- IGF-1
- Longevity
- Microbiota
- mtDNA
- mTOR
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Pharmacology
- Medicine(all)
Cite this
Genes of human longevity : An endless quest? / Capri, Miriam; Santoro, Aurelia; Garagnani, Paolo; Bacalini, Maria Giulia; Pirazzini, Chiara; Olivieri, Fabiola; Procopio, Antonio; Salvioli, Stefano; Franceschi, Claudio.
In: Current Vascular Pharmacology, Vol. 12, No. 5, 2014, p. 707-717.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genes of human longevity
T2 - An endless quest?
AU - Capri, Miriam
AU - Santoro, Aurelia
AU - Garagnani, Paolo
AU - Bacalini, Maria Giulia
AU - Pirazzini, Chiara
AU - Olivieri, Fabiola
AU - Procopio, Antonio
AU - Salvioli, Stefano
AU - Franceschi, Claudio
PY - 2014
Y1 - 2014
N2 - Human longevity is a complex trait in which genetics, epigenetics, environmental and stochasticity differently contribute. To disentangle the complexity, our studies on genetics of longevity were, at the beginning, mainly focused on the extreme phenotypes, i.e. centenarians who escaped the major age-related diseases compared with cross sectional cohorts. Recently, we implemented this model by studying centenarians’ offspring and offspring of non-long lived parents. In association, during studies on many candidate genes SNPs, positively or negatively correlated with longevity have been identified. The results obtained on Insulin-like Growth Factor 1 Receptor (IGF1R) polymorphisms showed a correlation between specific genetic variants combinations and the low plasma level of IGF1 in centenarians, suggesting an impact of the IGF-I/insulin pathway on human longevity. This pathway together with mammalian target of rapamycin (mTOR) will be reviewed as being the most promising for longevity. Further, we will summarise the role of apolipoprotein E (APOE) variants in human longevity since the results of the large European project GEHA (Genetics of Healthy Aging) indicate APOE among the chromosomal loci associated with longevity. On the other hand, the identification of longevity-related genes does not explain the mechanisms of healthy aging and longevity rather pose questions on epigenetic contribution, gene regulation and the interactions with essential genomes, i.e. mitochondrial DNA and microbiota. To fully disentangle what appears to be an endless quest, all the components of the complexity of human longevity genetics are taken into account.
AB - Human longevity is a complex trait in which genetics, epigenetics, environmental and stochasticity differently contribute. To disentangle the complexity, our studies on genetics of longevity were, at the beginning, mainly focused on the extreme phenotypes, i.e. centenarians who escaped the major age-related diseases compared with cross sectional cohorts. Recently, we implemented this model by studying centenarians’ offspring and offspring of non-long lived parents. In association, during studies on many candidate genes SNPs, positively or negatively correlated with longevity have been identified. The results obtained on Insulin-like Growth Factor 1 Receptor (IGF1R) polymorphisms showed a correlation between specific genetic variants combinations and the low plasma level of IGF1 in centenarians, suggesting an impact of the IGF-I/insulin pathway on human longevity. This pathway together with mammalian target of rapamycin (mTOR) will be reviewed as being the most promising for longevity. Further, we will summarise the role of apolipoprotein E (APOE) variants in human longevity since the results of the large European project GEHA (Genetics of Healthy Aging) indicate APOE among the chromosomal loci associated with longevity. On the other hand, the identification of longevity-related genes does not explain the mechanisms of healthy aging and longevity rather pose questions on epigenetic contribution, gene regulation and the interactions with essential genomes, i.e. mitochondrial DNA and microbiota. To fully disentangle what appears to be an endless quest, all the components of the complexity of human longevity genetics are taken into account.
KW - APOE
KW - ELOVL2
KW - Epigenetics
KW - IGF-1
KW - Longevity
KW - Microbiota
KW - mtDNA
KW - mTOR
UR - http://www.scopus.com/inward/record.url?scp=84924091788&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924091788&partnerID=8YFLogxK
M3 - Article
C2 - 24350927
AN - SCOPUS:84924091788
VL - 12
SP - 707
EP - 717
JO - Current Vascular Pharmacology
JF - Current Vascular Pharmacology
SN - 1570-1611
IS - 5
ER -