Thursday, 24 May 2012

The PGC-1 Homolog and Longevity in Drosophila melanogaster

The common fruit fly, Drosophila melanogaster, is a model organism heavily studied in genetics. Its short life cycle and generation times make it a particularly useful model for genetic studies in longevity. After the genome of Drosophila melanogaster was sequenced in 2001 it has been possible for scientists to identify individual genes and alter them. With as many as 60% of their genes shared with homologous genes in humans1, and almost 75% of disease-causing genes2, studies in the longevity of Drosophila melanogaster have potential implications for human aging.


Drosophila melanogaster - SEM (SciencePhotoLibrary)
Researchers at the University of California, Los Angeles, collaborating with stem cell researchers at the Salk Institute for Biological Studies (SIBS) have found a way to slow aging in the fruit fly Drosophila melanogaster by altering the fly’s version of the gene PGC-1. The 2011 study, Modulation of Longevity and Tissue Homeostasis by the Drosophila PGC-1 Homolog, found that aging could be slowed by up to 50 percent by increasing the activity of the gene in the stem cells of the fruit fly’s intestine; said by the lead scientist of SIBS, Leanne Jones, to have a high degree of similarity to a human’s small intestine3. PGC-1, a homologous gene found in humans and all mammals, known as dPGC-1 in Drosophila fruit flies, regulates energy metabolism such as mitochondrial energy.

As an organism ages, mitochondrion; the energy-producing powerhouses of the cell, become less efficient and active. Less of mitochondrial activity, which cellular functions depend on, means cellular functions degrade. In Drosophila and mammals alike, this decrease in PGC-1 and mitochondrial activity has a clear link with aging, though it is still not clear what causes aging at the cellular level. In Drosophila, more mitochondrial activity, caused by increasing the activity of the dPGC-1 gene, has an opposite effect. The increased activity of mitochondrion stimulates the stem cells that repair and renew intestinal tissue, leading to a slower-aging and healthier intestine.


The breaking down of intestinal stem cells that the overexpression of the dPGC-1 gene delays
(Image: Salk Institute for Biological Studies)

Researchers also tried activating the gene in other tissue types such as neurons and muscle but found no such effect on longevity4. The study shows that a single organ such as the intestine, one that has been speculated to play a central role in aging, when modified by the overexpression of dPGC-1 has an effect of slowing the aging process and increasing longevity at the level of the entire organism, not just in the organ itself. In using a model organism such as Drosophila melanogaster with genes homologous to humans, though only preliminary to possible applications, the study raises questions about using the PGC-1 gene to combat human aging and aging-related diseases in the quest to extend human longevity.

Bibliography

Fruit fly intestine may hold secret to the fountain of youth 2011, viewed 18 March 2012, <http://www.sciencedaily.com/releases/2011/11/111109093945.htm >

Rera, M et al. 2011, ‘Modulation of Longevity and Tissue Homeostasis by the Drosophila PGC-1 Homolog’, Cell Metabolism 14, viewed 16 March, 2012, <http://www.cell.com/cell-metabolism/abstract/S1550-4131(11)00388-3>*


References

1 National Human Genome Research Project 2002, Background on Comparative Genomic Analysis, viewed 18 March 2012, <http://www.genome.gov/10005835>

2 Reiter LT et al. 2001, ‘A Systematic Analysis of Human Disease-Associated Gene Sequences In Drosophila melanogaster’, Genome Res., volume 11, viewed 19 March, 2012, <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC311089/>

3 Fruit Fly Intestine May Hold Secret to Fountain of Youth: Long-Lived Fruit Flies Offer Clues to Slowing Human Aging and Fighting Disease 2011, viewed 18 March 2012, <http://www.sciencedaily.com/releases/2011/11/111102161156.htm>

4 Rera, M et al. 2011, ‘Modulation of Longevity and Tissue Homeostasis by the Drosophila PGC-1 Homolog’, Cell Metabolism, volume 14, p. 625, viewed 16 March, 2012, <http://www.cell.com/cell-metabolism/abstract/S1550-4131(11)00388-3>

Brodie Foster - 42848387

No comments:

Post a Comment