Transcription factor Pha-4

by Séverine Altairac

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Life is something not many of us are ready to lose. From elixirs to genetic tinkering, over the years humans have searched for ways of lengthening our time here on Earth. Some have even tried to define what the process of getting older actually is. Is it a way of ensuring that the younger – and hence the fittest – get a decent go at reproducing and not their ageing parents? Or is it the result of an accumulation of negative events – such as mutations – ultimately leading to death? Or are we given a certain amount of energy to be spent in a lifetime, which is distributed between reproducing and maintaining our organism?

No one is in a position to give a definite answer yet. Perhaps no one ever will be. However, it is becoming quite clear that there are genes which have direct roles in an organism’s lifespan. One such gene is known as Pha-4 whose product is the protein transcription factor Pha-4. And it is found in the worm Caenorhabditis elegans.

Pha-4 has two roles. It is involved in C.elegans embryogenesis and, more specifically, in the proper development of its pharynx. When C.elegans is an adult, however, Pha-4 has a very different activity – when the worm is put onto a calorie-restricted diet, Pha-4 bestows on the worm the faculty to live a little longer. How? The precise mechanism is still poorly understood but in environments where there is enough food, albeit poor in calories, the transcription factor stimulates the production of other proteins involved in the worm’s energy homeostasis.

The effect of a calorie-restricted diet on an organism’s lifespan is nothing new; it had already made the headlines in the 1930s. What is new, however, is that researchers have managed to put their finger on a gene which is directly linked to how long a worm will stick around...

Could something of the like exist in humans? Perhaps. Pha-4 is similar to what is known as the FoxA family of proteins, and FoxA proteins are involved in glucose homeostasis – an important source of energy. Yet again though, humans are not worms and things are not so simple. Will one sole gene ever prove to be the switch for ‘staying young’ or ‘getting old’? It is hard to believe. In between times, there is nothing to prevent us from keeping to a calorie-restricted diet. You never know.

UniProt cross references
Defective pharyngeal development protein 4, Caenorhabditis elegans: Q17381
Protein Spotlight (ISSN 1424-4721) is a monthly review written by the Swiss-Prot team of the SIB Swiss Institute of Bioinformatics. Spotlight articles describe a specific protein or family of proteins on an informal tone. Follow us: Subscribe · Twitter · Facebook