# LIFESPAN ENHANCING MUTATIONS IN C ELEGANS

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 1993 · $191,788

## Abstract

We recently discovered that sperm production in the nematode
Caenorhabditis elegans reduces male lifespan, and that mutations in the
spermatogenesis-defective gene, spe-26, can increase average lifespan 35
to 100% (Van Voorhies, 1992, Nature in press). Thus this gene has the
largest effect on lifespan of any gene so far identified in C. elegans.
The gene has been cloned, and both wild-type and mutant genes have been
completely sequenced. This proposal is to extend and utilize these
findings to learn more about how sperm production and the spe-26 gene
influence aging, and to take advantage of the cloned spe-26 gene to extend
life-span by transformation of worms with altered spe-26 clones. C.
elegans has many advantages for genetic analysis of the fundamental causes
of aging, including short generation time, ease of culture, homozygous
wild-type strain, detailed knowledge of its development, sophisticated
genetics, small genome with an extensive genetic map and nearly complete
physical map, and methods for gene tagging and for DNA transformation.
Thus it is well suited for analysis of either Longevity Assurance Genes,
that normally act to increase lifespan, or Aging Genes, like spe-26, that
must be mutated to increase lifespan. The specific aims of this proposal
are as follows. (l) Determine if the lifespan increase caused by spe-26
mutations is mediated solely by their effect on spermatogenesis or if the
phenotypes are distinct functions of the same gene. This will be done by
characterization of additional mutations and analysis of the sequences
responsible for tissue specific gene regulation. (2) Increase the lifespan
of wild-type C. elegans by creating transgenic strains that disrupt the
normal spe-26 gene by transformation with DNA constructs encoding either
spe-26 antisense RNA or dominant negative mutant proteins. This is the
most important experiment in terms of the goals of the "Genetic and
Molecular Basis of Longevity" program because it would demonstrate that
lifespan can be increased by disrupting a normal aging gene in a
transgenic animal, a model that could be applied to humans. (3) Find genes
similar in function to spe-26 in other organisms by searching for genes
similar in sequence. This will be done by low stringency hybridization and
PCR amplification with spe-26 primers to see if spe-26 homologues can be
found in other animals including mammals. (4) Determine if other mutations
affecting spermatogenesis alter C. elegans lifespan. We will take
advantage of our laboratory's more than 50 spermatogenesis-defective genes
ordered into a developmental pathway to see exactly when during
spermatogenesis and under control of which genes does lifespan become
reduced. This proposal is directly relevant to human health because
fundamental mechanisms of aging may be found and mammalian and human
homologues of spe-26 may be identified, and, most importantly, because
establishing that lifespan can be increased by transgenic disruption of
aging ge...

## Key facts

- **NIH application ID:** 3123560
- **Project number:** 1R01AG011659-01
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **SAM.gov UEI:** ED44Y3W6P7B9
- **Principal Investigator:** SAMUEL WARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $191,788
- **Award type:** 1
- **Project period:** 1993-08-15 → 1998-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123560

## Citation

> US National Institutes of Health, RePORTER application 3123560, LIFESPAN ENHANCING MUTATIONS IN C ELEGANS (1R01AG011659-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123560. Licensed CC0.

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