Ageing and metabolic controls

Ageing is of interest to everyone, except the young who welcome growing older and those who don’t make old age.
Many ageing related genes which alter longevity for good or bad have been identified. A gene that influences ageing is the daf-16 gene which is called a gerontogene.
The protein encoded by daf-16 is a transcription factor which modifies the activity of other genes. This gene in the C.elegans worm and mice is a powerful influence on life span.
Daf-16 is turned off by hormonal signalling pathways similar to insulin and insulin growth factor.
There are two classes of genes affected by Daf-16
Class -1 genes ( there are 189 of these) are switched on and are associated with increased life span
Class -2genes ( there are 122 of these) are repressed and are associated with reduced life span
The effect of Daf-16 is additive and requires the combined activity of many of these genes.
So what is a ageing. Is it the accumulation of metabolic rubbish? ( It feels like this ) or some other process ? Or some as yet unthought of process.
It is interesting that a recent blog that I wrote confidently proposed that ageing was accumulated DNA damage,
Of interest to all of us.
Gems and McElwee Nature 2003, vol 424, 259-261
Murphy et al Nature 2003, vol 424, 277-283

Martin Eastwood
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