Fruit Fly Work Identifies New Possibility for Drugs to Combat Ageing
Gavin Hubbard, 12th November 2011
Artists impression of an aged fruit fly.
Original picture by "Image Editor"
Scientists at the University of California, Los Angeles (UCLA) have identified a potential new target in the fight against ageing, as well as shedding some light on the role of the digestive system in ageing.
The work investigated the role of a gene called PGC-1. PGC-1 regulates the activity of mitochondria; small organelles within cells that are involved in metabolism and cell death.
Mitochondria’s role in energy production and metabolism may be particularly important because it affects a wide range of cellular processes, as such, any change in the number or activity of mitochondria is likely to have widespread consequences within the cell, and therefore, potentially the entire organism.
(See our blog post for more info’ on mitochondria)
Previous work on fruit flies, that deliberately caused a loss of function of PGC-1, had shown that it was important for the normal functioning of mitochondria. So, the team reasoned, an increase in PGC-1 could lead to an increase in mitochondrial activity or number.
To test this they deliberately up-regulated the activity of the gene and then measured the amount of mitochondrial DNA (mtDNA), a marker of abundance, and citrate synthase, a marker of activity, in the modified flies and compared them to normal flies.
They found almost a two-fold increase in mtDNA in the modified fly larvae and an increase of just over 50% in the modified adult fly compared to flies with no up-regulation. Similar increases were seen for citrate synthase.
Using a number of techniques the team then sought to determine if the increased expression of PGC-1 had an effect on the usually 2 month long life span of the fruit flies.
They investigated if PGC-1 up-regulation in the whole fly or in specific tissues – such as neurons and muscle, among others – had any effect on the life span of the fly.
Only in the tissues of the digestive tract did they find an increase in longevity of the flies, by up to 50%*.
By using food containing a blue dye the researchers showed that the intestine of normal flies loses integrity as they age; the blue dye leaked throughout rest of the fly. While flies with up-regulated PGC-1 in their intestines, at the same age, has less leakage with blue mainly local to their digestive tracts only.
Speaking to the UCLA News room, David Walker, part of the UCLA team involved in the study said "By activating this one gene in this one tissue — the intestine — the fly lives longer; we slow aging of the intestine, and that has a positive effect on the whole animal, Our study shows that increasing PGC-1 gene activity in the intestine can slow aging, both at the cellular level and at the level of the whole animal."
The study also raises questions about the role of energy metabolism and the digestive system in ageing. Some studies, in humans, have shown that a calorie restricted diet does result in some increase of longevity and a reduction in some diseases, usually associated with ageing.
Ageing is the primary risk factor for a number of cancers as well as diseases like arthritis, osteoporosis, type 2 diabetes and hypertension among others. PGC-1 could be a target for drugs to modulate the cellular signs of ageing and, therefore, diseases associated with age.
*That’s 50% more time for them to inexplicably zoom about inches from your face when 95% of the volume of a room is otherwise empty…
The work investigated the role of a gene called PGC-1. PGC-1 regulates the activity of mitochondria; small organelles within cells that are involved in metabolism and cell death.
Mitochondria’s role in energy production and metabolism may be particularly important because it affects a wide range of cellular processes, as such, any change in the number or activity of mitochondria is likely to have widespread consequences within the cell, and therefore, potentially the entire organism.
(See our blog post for more info’ on mitochondria)
Previous work on fruit flies, that deliberately caused a loss of function of PGC-1, had shown that it was important for the normal functioning of mitochondria. So, the team reasoned, an increase in PGC-1 could lead to an increase in mitochondrial activity or number.
To test this they deliberately up-regulated the activity of the gene and then measured the amount of mitochondrial DNA (mtDNA), a marker of abundance, and citrate synthase, a marker of activity, in the modified flies and compared them to normal flies.
They found almost a two-fold increase in mtDNA in the modified fly larvae and an increase of just over 50% in the modified adult fly compared to flies with no up-regulation. Similar increases were seen for citrate synthase.
Using a number of techniques the team then sought to determine if the increased expression of PGC-1 had an effect on the usually 2 month long life span of the fruit flies.
They investigated if PGC-1 up-regulation in the whole fly or in specific tissues – such as neurons and muscle, among others – had any effect on the life span of the fly.
Only in the tissues of the digestive tract did they find an increase in longevity of the flies, by up to 50%*.
By using food containing a blue dye the researchers showed that the intestine of normal flies loses integrity as they age; the blue dye leaked throughout rest of the fly. While flies with up-regulated PGC-1 in their intestines, at the same age, has less leakage with blue mainly local to their digestive tracts only.
Speaking to the UCLA News room, David Walker, part of the UCLA team involved in the study said "By activating this one gene in this one tissue — the intestine — the fly lives longer; we slow aging of the intestine, and that has a positive effect on the whole animal, Our study shows that increasing PGC-1 gene activity in the intestine can slow aging, both at the cellular level and at the level of the whole animal."
The study also raises questions about the role of energy metabolism and the digestive system in ageing. Some studies, in humans, have shown that a calorie restricted diet does result in some increase of longevity and a reduction in some diseases, usually associated with ageing.
Ageing is the primary risk factor for a number of cancers as well as diseases like arthritis, osteoporosis, type 2 diabetes and hypertension among others. PGC-1 could be a target for drugs to modulate the cellular signs of ageing and, therefore, diseases associated with age.
*That’s 50% more time for them to inexplicably zoom about inches from your face when 95% of the volume of a room is otherwise empty…
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