Caenorhabditis elegans, commonly known as C.elegans, are tiny ringworms living in temperate soil environments. A recent research, conducted at the Thomas Jefferson University, has revealed that the level of a single protein called arrestin; in the tiny roundworm C elegans determines how long it lives. The research further explained, that worms born without arrestin, may live about one-third than normal but worms that had triple the amount of it, lived one-third less.
Arrestin is known to interact with several other proteins within cells to regulate longevity. The human body also, has a similar protein present. It is termed as PTEN and is a well known tumor suppressor. This was revealed by Jeffrey L. Benovic, Ph.D., professor and chair of the department. The investigators also noted that, since most proteins in worms, complement human proteins, the research may be relevant to human biology and cancer development too.
The researchers insisted, on using the roundworm as a model because it is a simpler form to analyse the function of genes and proteins that are relevant to human biology. This is because the worm has one arrestin gene, whereas humans have four. Also, the worms have 302 neurons, while the human brain has 100 billion neurons or so. Moreover, the worms have a short lifespan of two to three weeks, which ensures timely observation of effects of longevity.
Dr. Benovic and the research’s first author, Aimee Palmitessa, Ph.D., a postdoctoral research person, thoroughly examined the signaling pathways activated by G protein-coupled receptors. These receptors are known to bind to all kinds of hormones, sensory stimuli (such as light, odorants and tastants), neurotransmitters, etc. They then activate a cascade of signals inside the cell. They are also assumed, to regulate many physiological processes. Almost, half of the drugs, which are currently available in the market, target these receptors for treatment.
Dr. Benovic stated, “When it comes to receptors, worms are actually more complex. Humans have about 800 different kinds of G protein-coupled receptors while the worm has about 1,800. It relies upon these receptors to respond to sensory stimuli as well as various neurotransmitters and hormones.”
Arrestins apparently, means that they arrest the activity of receptors. The arrestins were found, to turn off the activation of G protein-coupled receptors inside the cells. In humans, two of the four arrestins regulate the receptors that, respond to visual stimuli. And the other two, regulate most of the other receptors. While conducting the research, Dr. Palmitessa, eliminated the single arrestin gene in worms, to see what would happen. Astonishingly, these worms lived longer. She also, caught sight of the fact that, over-expressing arrestin in worms, shortened their lifespan.
However, regarding longevity, in worms this is not a maiden discovery. Prior researchers have long before discovered that, activity of the insulin-like growth factor-1 (IGF-1) receptor can influence longevity in worms. But, this finding has been replicated in fruit flies, mice, and humans also. Just like arrestin, a little less IGF-1 receptor activity is probably good. Research has even shown that, caloric restriction can also reduce IGF-1 receptor activation. Some human cancer indicated the presence of the IGF-1 receptor.
However, the research led by Dr. Benovic and Dr. Palmitessa seems to be more detailed. It has found that, arrestin interacted with two other proteins in worms. This plays a critical role in its ability to regulate longevity. Amongst this, one protein is PTEN, which suppresses tumor. Mutations in PTEN also, claim to be involved in various types of cancers.
But Dr. Benovic approved, that the connection between human arrestin and PTEN is not known. Researchers have still not been able to know, that in humans, do arrestins regulate PTEN function or does something happen to the arrestin levels when cancer is developed. Do the increase levels turn off more PTEN thus increasing cancer? Or does a decrease in the level allow PTEN to be more active? Too many questions may be left unanswered. Dr. Benovic shared that in case it turns out that the amounts of arrestin turn off the tumor suppressor activity of PTEN, then it may be possible to selectively inhibit that process.
The research will be published in the online edition of the Journal of Biological Chemistry.