Genetics, lifestyle and longevity: Lessons from centenarians

Abstract

Longevity as a complex life-history trait shares an ontogenetic relationship with other quantitative traits and varies among individuals, families and populations. Heritability estimates of longevity suggest that about a third of the phenotypic variation associated with the trait is attributable to genetic factors, and the rest is influenced by epigenetic and environmental factors. Individuals react differently to the environments that they are a part of, as well as to the environments they construct for their survival and reproduction; the latter phenomenon is known as niche construction. Lifestyle influences longevity at all the stages of development and levels of human diversity. Hence, lifestyle may be viewed as a component of niche construction. Here, we: a) interpret longevity using a combination of genotype-epigenetic-phenotype (GEP) map approach and niche-construction theory, and b) discuss the plausible influence of genetic and epigenetic factors in the distribution and maintenance of longevity among individuals with normal life span on the one hand, and centenarians on the other. Although similar genetic and environmental factors appear to be common to both of these groups, exceptional longevity may be influenced by polymorphisms in specific genes, coupled with superior genomic stability and homeostatic mechanisms, maintained by negative frequency-dependent selection. We suggest that a comparative analysis of longevity between individuals with normal life span and centenarians, along with insights from population ecology and evolutionary biology, would not only advance our knowledge of biological mechanisms underlying human longevity, but also provide deeper insights into extending healthy life span.

Keywords: Composite trait; Genomic stability; Genotype–phenotype (G–P) map; Negative frequency-dependent selection; Niche construction; Reaction norms.

Fig. 1

Human life expectancy through the ages. Note the average life expectancy among foragers has not changed much. Figure modified from Finch (2007) with permission.

Fig. 2

Comparison between the average life span of centenarians in a British cohort, relative to average life expectancy among contemporary human populations. Mean death age of British centenarians and the average life expectancy of global populations differ by 3.0 SDs (Evans et al., 2014, Annonymous, 2012).

Fig. 3

Calorie restriction as an example of life-style modification and its plausible effects on the genetic–epigenetic–phenotypic spaces (Barzilai et al., 2012).

Fig. 4

Age related genotype frequencies of six genes in the Ashkenazi centenarian cohort (Barzilai et al., 2012).