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

Area of Science:

• Biomedicine
• Genetics
• Gerontology

Background:

• Human longevity is a complex trait with poorly understood genetic underpinnings.
• Previous studies have yielded disappointing results due to the complexity of the longevity phenotype.
• Gene-environment interactions are crucial for reaching extreme human lifespan.

Purpose of the Study:

• To provide an integrated, ecological, and evolutionary perspective on the genetics of human longevity.
• To scrutinize literature, emphasizing often-neglected factors like sex, ancestry, and socioeconomic status.
• To discuss the strengths and limitations of genome-wide association study and whole-genome sequencing in longevity research.

Main Methods:

• Literature review and critical analysis of existing studies on human longevity.
• Focus on under-investigated factors influencing longevity, including social and environmental determinants.
• Discussion of genetic tools like genome-wide association study and whole-genome sequencing.

Main Results:

• Genetics of longevity is highly population-specific.
• Small-effect alleles, pleiotropy, and complex allele timing are significant.
• Genetic risk factors are age-specific and linked to age-related diseases, particularly cardiovascular diseases.

Conclusions:

• A comprehensive approach integrating nuclear, mitochondrial, and microbiome genetics is urgently needed.
• Understanding longevity requires considering gene-environment interactions within ecological and evolutionary frameworks.
• Future research should focus on population-specific genetics and the interplay with age-related diseases.