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The Snell dwarf mutation Pit1(dw) can increase life span in mice
Kevin Flurkey1, John Papaconstantinou, David E Harrison
1The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Mechanisms of Ageing and Development
|November 24, 2001
Summary
The Snell dwarf mutation significantly extends lifespan in female mice and some male mice. Environmental factors, like housing conditions, interact with this mutation to influence aging and mortality rates.
Area of Science:
- Genetics
- Gerontology
- Endocrinology
Background:
- The Snell dwarf mutation (Pit1(dw)) has shown variable effects on lifespan across studies.
- Previous research reported conflicting outcomes regarding the mutation's impact on longevity.
Purpose of the Study:
- To investigate the precise effects of the Snell dwarf mutation on lifespan.
- To clarify the influence of genetic background and environmental factors on aging in Snell dwarf mice.
Main Methods:
- Comparative lifespan analysis of Snell dwarf mice (Pit1(dw)/Pit1(dw) and Pit1(dw)/Pit1(dw-J) genotypes) with control groups.
- Evaluation of life span data including mean, median, and maximum longevity.
- Assessment of environmental influences, specifically housing conditions, on dwarf male lifespan.
Main Results:
- Snell dwarf (Pit1(dw)/Pit1(dw)) DW/J females exhibited a 40-50% increase in mean, median, and maximum life spans.
- Compound heterozygous dwarf mice (Pit1(dw)/Pit1(dw-J)) showed 25-50% increases in lifespan.
- Previously observed shortened lifespan in Snell dwarf males was attributed to housing conditions, not the mutation itself; males housed with females achieved significantly longer lifespans.
Conclusions:
- The Snell dwarf mutation's effect on lifespan is highly variable and depends on interactions with environmental factors.
- A trade-off between physical vigor and lifespan, mediated by pituitary hormones (growth hormone, thyroid hormone, prolactin), is proposed to regulate mortality schedules.