Genes of human longevity: an endless quest?

Area of Science:

• Genetics of aging
• Human longevity research
• Complex trait analysis

Background:

• Human longevity is influenced by a complex interplay of genetics, epigenetics, and environmental factors.
• Early studies focused on extreme longevity phenotypes like centenarians.
• Recent research includes offspring of long-lived and non-long-lived individuals to refine genetic models.

Purpose of the Study:

• To identify genetic variants associated with human longevity.
• To explore the role of specific pathways, such as IGF-I/insulin and mTOR, in aging.
• To investigate the contribution of apolipoprotein E (APOE) variants to healthy aging.

Main Methods:

• Analysis of single nucleotide polymorphisms (SNPs) in candidate genes.
• Comparison of genetic profiles in centenarians and control cohorts.
• Inclusion of offspring studies to validate genetic associations.

Main Results:

• Specific combinations of Insulin-like Growth Factor 1 Receptor (IGF1R) polymorphisms correlate with lower IGF1 plasma levels in centenarians.
• The IGF-I/insulin pathway and mammalian target of rapamycin (mTOR) are highlighted as promising targets for longevity research.
• Apolipoprotein E (APOE) variants are identified as significant chromosomal loci associated with longevity.

Conclusions:

• Genetic factors, including IGF1R and APOE variants, play a significant role in human longevity.
• Understanding genetic contributions is crucial but does not fully explain healthy aging mechanisms.
• Further research is needed to integrate epigenetic, gene regulation, and interactions with mitochondrial DNA and microbiota.