Genetic Factors and Epigenetic Mechanisms of Longevity: Current Perspectives

Abstract

The exceptional longevity phenotype, defined as living beyond the age of 95, results from complex interactions between environmental and genetic factors. Epigenetic mechanisms, such as DNA methylation and histone modifications, mediate the interaction of these factors. This review will provide an overview of animal model studies used to examine age-related epigenetic modifications. Key human studies will be used to illustrate the progress made in the identification of the genetic loci associated with exceptional longevity, including APOE and FOXO3 and genes/loci that are also differentially methylated between long-lived individuals and younger controls. Future studies should focus on elucidating whether identified longevity genetic loci directly influence epigenetic mechanisms, especially on differentially methylated regions associated with longevity.

Keywords::

• aging
• DNA methylation
• epigenetic
• genome-wide association studies
• histone modification
• longevity
• neurodegenerative disease

Financial & competing interests disclosure

J Kwok was supported by NHMRC grant APP1021269. J Lazarus is supported by the Cowled Postgraduate Scholarship in Brain Research. K Mather is supported by an Alzheimer’s Australia Dementia Research Foundation Postdoctoral Fellowship and the NHMRC Capacity Building Grant 568940. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

J Kwok was supported by NHMRC grant APP1021269. J Lazarus is supported by the Cowled Postgraduate Scholarship in Brain Research. K Mather is supported by an Alzheimer’s Australia Dementia Research Foundation Postdoctoral Fellowship and the NHMRC Capacity Building Grant 568940. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.