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A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae

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Published on: September 17, 2020

Genetic variation and human longevity.

Mette Soerensen¹

¹Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 9B, 5000 Odense C, Denmark. msoerensen@health.sdu.dk

Danish Medical Journal

|May 3, 2012

Summary

This summary is machine-generated.

This study investigated genetic variations in longevity pathways and candidate genes using a pathway approach. Findings suggest specific genes like APOE, CETP, IL6, INS, RAD52, and NTHL1 are associated with human longevity.

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Published on: September 29, 2011

Area of Science:

Genetics
Gerontology
Molecular Biology

Background:

Human longevity is influenced by genetic factors, but specific genes and pathways remain incompletely understood.
Previous studies often used case-control designs, susceptible to bias; a prospective approach is needed for robust genetic association studies in aging populations.

Purpose of the Study:

To elucidate the association of human longevity with genetic variation in major candidate genes and longevity pathways.
To identify novel genetic variants and pathways contributing to exceptional survival.
To investigate the role of genetic variation in survival during advanced age using longitudinal and case-control designs.

Main Methods:

A pathway-based approach was used, selecting 168 genes involved in DNA damage signaling, DNA repair, GH/IGF-1/insulin signaling, and antioxidant pathways, plus 16 additional candidate genes.
Tagging single nucleotide polymorphisms (SNPs) were selected using the HapMap Consortium to cover common genetic variation.
Genotyping was performed on 2,000 individuals from the Danish 1905 birth cohort (oldest-old) and the Study of Middle-aged Danish twins (MADT), followed by longitudinal and case-control analyses.

Main Results:

SNPs in APOE, CETP, and IL6 were associated with longevity, confirming known candidates.
Novel associations with longevity were found for SNPs in INS, RAD52, and NTHL1.
Replication studies confirmed findings, revealing that rare alleles often act as longevity variants and highlighting sex-specific genetic effects on survival.

Conclusions:

Genetic variations in specific genes and pathways significantly contribute to human longevity.
The study identified novel candidate genes (INS, RAD52, NTHL1) and confirmed roles for others (APOE, CETP, IL6, FOXO3A).
Longevity appears influenced by positively acting minor alleles and exhibits sex-specific genetic modulation, warranting further investigation into gene expression and regulatory mechanisms.