# POLYMORPHIC GENES MODULATING LIFESPAN IN C ELEGANS

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 1991 · $136,237

## Abstract

A novel strategy is proposed to identify and initially characterize genes
and interacting groups of genes which determine adult lifespan in the
nematode C. elegans.  The F1 progeny of crosses between C. elegans strains
(e.g., N2xBO or N2xDH424) have lifespans similar to the parental strains,
and yet F2's and derived inbred clones show increased variation in
lifespans, which range from 70-160% of parental levels.  This implies that
multiple genes, polymorphic between these strains, determine C. elegans
lifespan.  We propose to characterize such genes by identifying alleles
consistently present in the longest-lived recombinant inbred progeny of
inter-strain crosses.  Unique probes flanking those Tc1 transposons which
are present in genomic DNA of the BO and DH424 strains, but absent from N2
and C12a, will be used to determine the source strain for homozygous
regions of (N2 or C12a)x(BO or DH424) hybrid genomes.  The allele ratio (-
Tc1:+Tc1) must be 1:1 in the F1 heterozygotes, and any consistent shift
between young worms at F1 and later generations would be attributed to
reproductive selection favoring one allele.  However, if a given allele
ratio changes consistently between young adults and the longest-lived 5% of
worms, both at the same generation (Fn greater than or equal to 12), this
would indicate linkage between that polymorphic marker and a lifespan
determining gene -- for which one of the two alleles conferred greater
lifespan than the other.  Polymerase chain reaction with multiplex primer
sets, specific for sequences flanking mapped Tc1 elements in BO and/or
DH424 DNA, will be used to analyze > 100 of the longest-surviving
individual worms in such populations, to identify combinations of gene
alleles which frequently co-segregate in long-lived worms.  Comparison of
these gene sets with those selected under conditions of hyperoxia or late
fecundity, etc., will indicate the extent of overlap between the underlying
genetic determinants for these traits.  Identification of lifespan-
modulating genes, and of alleles with differing contributions to longevity,
will aid our understanding of the molecular mechanisms underlying
senescence.  In the long term, comparative studies of cognate genes in
other species, including man, should reveal whether they share a common
mechanism of senescence, and may implicate genetic interactions in the
etiology of age-associated diseases.

## Key facts

- **NIH application ID:** 3121263
- **Project number:** 1R01AG009413-01A1
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **SAM.gov UEI:** VDFYLZPJEAV6
- **Principal Investigator:** Robert Joseph Shmookler Reis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $136,237
- **Award type:** 1
- **Project period:** 1991-08-15 → 1996-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121263

## Citation

> US National Institutes of Health, RePORTER application 3121263, POLYMORPHIC GENES MODULATING LIFESPAN IN C ELEGANS (1R01AG009413-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121263. Licensed CC0.

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