The Three Genetics (Nuclear DNA, Mitochondrial DNA, and Gut Microbiome) of Longevity in Humans Considered as Metaorganisms

Garagnani, Paolo; Pirazzini, Chiara; Giuliani, Cristina; Candela, Marco; Brigidi, Patrizia; Sevini, Federica; Luiselli, Donata; Bacalini, Maria Giulia; Salvioli, Stefano; Capri, Miriam; Monti, Daniela; Mari, Daniela; Collino, Sebastiano; Delledonne, Massimo; Descombes, Patrick; Franceschi, Claudio

doi:10.1155/2014/560340

Cited by 27 publications

(10 citation statements)

References 147 publications

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“…Intriguingly, these bacteria were found to characterize the GM in extreme longevity [ 8 ], thus reinforcing the idea of a close association with the genetic background and suggesting a possible link to the inheritable component of human longevity. Nuclear, also mitochondrial, DNA plays a major role in the aging process so the complex interaction between these two host genetics [ 159 ] should be taken into account if we are to properly address the GM remodeling occurring during the human life span.…”

Section: Gut Microbiota and Host Genetics: An Intimate Evolutionary-smentioning

confidence: 99%

“…Many variables may be responsible for GM remodeling associated with human longevity. Among these, the genetic makeup of extreme longevity [ 159 , 167 ], and the epigenetic changes associated with aging could have a deep impact together with nutrition and lifestyle habits. These lifelong interactions by variables are expected to have significant outputs in the production of specific blood/urine biomarkers or longevity-associated metabotypes.…”

Section: Gut Microbiota and Host Genetics: An Intimate Evolutionary-smentioning

confidence: 99%

See 1 more Smart Citation

Gut microbiota changes in the extreme decades of human life: a focus on centenarians

Santoro

Ostan

Candela

et al. 2017

Cell. Mol. Life Sci.

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199

103

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The gut microbiota (GM) is a complex, evolutionarily molded ecological system, which contributes to a variety of physiological functions. The GM is highly dynamic, being sensitive to environmental stimuli, and its composition changes over the host’s entire lifespan. However, the basic question of how much these changes may be ascribed to variables such as population, diet, genetics and gender, and/or to the aging process per se is still largely unanswered. We argue that comparison among studies on centenarians—the best model of healthy aging and longevity—recruited from different geographical areas/populations (different genetics and dietary habits) can help to disentangle the contribution of aging and non-aging-related variables to GM remodeling with age. The current review focuses on the role of population, gender and host genetics as possible drivers of GM modification along the human aging process. The feedback impact of age-associated GM variation on the GM–brain axis and GM metabolomics is also discussed. We likewise address the role of GM in neurodegenerative diseases such as Parkinson’s and Alzheimer’s, and its possible therapeutic use, taking advantage of the fact that centenarians are characterized by an extreme (healthy) phenotype versus patients suffering from age-related pathologies. Finally, it is argued that longitudinal studies combining metagenomics sequencing and in-depth phylogenetic analysis with a comprehensive phenotypic characterization of centenarians and patients using up-to-date omics (metabolomics, transcriptomics and meta-transcriptomics) are urgently needed.

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Section: Gut Microbiota and Host Genetics: An Intimate Evolutionary-smentioning

confidence: 99%

Section: Gut Microbiota and Host Genetics: An Intimate Evolutionary-smentioning

confidence: 99%

Gut microbiota changes in the extreme decades of human life: a focus on centenarians

Santoro

Ostan

Candela

et al. 2017

Cell. Mol. Life Sci.

Self Cite

199

103

View full text Add to dashboard Cite

show abstract

“…Such trajectories increase the complexity of the study of genetics of longevity because indicate that the effect of a given allele varies according to the changes of the internal environment that occur from young and adults to the oldest old 140,141 . This feature, called "complex allele timing" by Benedictis and Franceschi (2006) points out the fact that genetic risks or protective factors are likely age-specific.…”

Section: Gwas Analysis Showed Monotonic As Well As Non-monotonic Age mentioning

confidence: 99%

Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework

Giuliani

Garagnani

Franceschi

2018

Circulation Research

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Genetics of human longevity within an eco-evolutionary nature-nurture framework. -Circulation Research 2018 ; 123(7) : 745-772.The final published version is available online at: https://www.ahajournals.org/ ABSTRACTHuman longevity is a complex trait, and to disentangle its basis has a great theoretical and practical consequence for biomedicine. The genetics of human longevity is still poorly understood, despite a number of investigations that used different strategies and protocols. Here we argue that such rather disappointing harvest is largely due to the extraordinary complexity of the longevity phenotype in humans. The capability to reach the extreme decades of human lifespan appears to be the result of an intriguing mixture of geneenvironment interactions. Accordingly, the genetics of human longevity is here described as a highly context-dependent phenomenon, within a new integrated, ecological and evolutionary perspective, and is presented as a dynamic process, both historically and individually. The available literature has been scrutinized within this perspective, paying particular attention to factors (sex, individual biography, family, population ancestry, social structure, economic status and education, among others) that have been relatively neglected. The strength and limitations of the most powerful and used tools, such as GWAS and whole-genome sequencing, have been discussed, focusing on prominently emerged genes and regions, such as APOE, FOXO3, IL-6, IGF-1, chromosome 9p21, 5q33.3 and somatic mutations among others. The major results of this approach suggest that: i) the genetics of longevity is highly population-specific; ii) small-effect alleles, pleiotropy and the "complex allele timing" likely play a major role; iii) genetic risk factors are age-specific and need to be integrated in the light of the geroscience perspective; iv) a close relationship between genetics of longevity and genetics of age-related diseases (especially cardiovascular diseases) do exist. Finally, the urgent need of a global approach to the largely unexplored interactions between the three genetics of human body, i.e. nuclear, mitochondrial and microbiomes, is stressed. We surmise that the comprehensive approach here presented will help in increasing the above-mentioned harvest.

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“…The geroscience concept as demonstrated by the work in Kulminski et al, suggests an alternative way forward in which seemingly different phenotypes could have a shared underlying genetic architecture. Important covariates may also be shared, including environment (nutrition, lifestyle, activity, population genetics), sex (since the aging trajectories of men and women are different), and epistatic interactions (including not only the nuclear genome but mitochondrial and microbial genomes) [7–8]. …”

Section: Introductionmentioning

confidence: 99%