Princeton University logoScientists have been using two vital methods to increase longevity of an organism. These include a method wherein, the intake of calorie consumption is considerably decreased and the other is in which, the activity of the hormone insulin is tweaked. Prior analysis have also suggested that, reduction in activity of the insulin-signaling pathway may help increase longevity of an organism. But, the Lewis-Sigler Institute for Integrative Genomics at Princeton claims to discover the novel evidence to prove that these mechanisms may affect the cognition function.

The researchers conducted this experiment on the roundworms C.elegans because they have a very simple nervous system. Also, they have a short span of just two-three weeks and these worms tend to experience signs of aging. They also display a reduction in motility and muscle deterioration, just like in other organisms including humans. The research aimed at determining the outcome of calorie restriction and reduction in insulin signaling on declines in learning and memory due to age.

Coleen Murphy, an assistant professor of molecular biology and the Lewis-Sigler Institute for Integrative Genomics at Princeton, and the senior author on the paper quoted, “The assumption in the field of longevity research has been that organisms able to live longer will function longer as well. It seems we need to revisit that. Different mechanisms of longevity extension may be beneficial to certain functions and detrimental to others, so it may be the case that treatments that target more than one longevity regulator will be the right approach to take.”

The investigators conducted huge experiments on these worms and thoroughly scrutinized each and every step. First, the scientists restricted calorie intake of the roundworms and registered a reduction in long-term memory loss in early adulthood. It was simultaneously noted that caloric restriction probably guards against memory loss over time. The worms with genetic mutations were also, examined. This helped the researchers to individually learn the impact of reducing the activity in the insulin-signaling pathway.

These worms displayed an improved long-term memory performance in early adulthood and even maintained good learning ability with age. But, they were not guarded against age-related declines in long-term memory. Higher organisms like mammals, were probably discovered with the same molecular mechanisms of cognitive function as those in the worms. Various experiments conducted by the authors, apparently helped identify several C. elegans mutants with long lifespans. They appeared to give opportunities to explore, the molecular and genetic pathways, which further allow these mutants to live up to 50 percent longer than normal worms.

It should be mentioned that, till date the scientists are unaware whether the decline in cognitive function because of age in humans is similar to the worms. And even if such a decline occurs, then do they affect mutant worms with long lifespans in the same way or on the same time scale, remains an unknown fact.

Therefore, to come up with answers, Princeton graduate student Amanda Kauffman trained the worms to associate foods. Their food consisted of bacteria named butanone. The worms were successfully trained to move towards this chemical with which they were fed. Once the training was accomplished, the scientists re-exposed the worms to their food to examine the learning and memory capacity of the worms. It then appeared that, after a single 30-minute training session, young worms moved toward butanone when tested immediately but didn’t when exposed less than 2 hours later.

A series of seven training sessions were undertaken, and then young worms were found to form long-term memories for as long as at least 16 hours. This time period is considered to be enormous since, these worms exist for only about two and a half weeks. When considered for an average person, this supposedly means that, for approximately three to six years he will enjoy the capacity of remembering something.

On the contrary, some tests seemed to conclude that, about half of this long-term memory faded within 24 hours. It was also noted that, after 40 hours of training the food-butanone association was completely vaporized from the minds of the worms. For the average person, this would equate to forgetting something after about eight to 15 years. Murphy apparently revealed that, the memory tests highlight the worms’ tendency to deprive the ability to learn and retain information. And all the deficits are most probably likely to appear in the second day of adulthood. The capacity of the worms to form long-term memories seemed to be lost completely by the fourth day of adulthood.

The research aimed to aid in introducing a treatment for people to live longer and at the same time avoid side effects like memory loss. Once, the learning and memory tests were conducted on normal worms, the scientists then headed to undertake the same test on two C. elegans mutants with abnormally long lifespans. A defect in the gene daf-2 was then noted in one of the mutants. This gene is probably known to control the formation of the worm’s insulin receptor. The worms’ ability to respond to the insulin hormone was reduced due to this defection. It is also believed that, the gene regulates survival and helps resist stress. It also aids in maintaining its mobility. In humans a similar gene is assumed to regulate aging.

On the other hand, the other mutant seemed to face a genetic defect which made it difficult to ingest food, therefore resulting in reduction in food intake of the worm. Scientists have always claimed that, restriction in calorie intake helps extend lifespan but the reasons of the same still seem to remain a mystery. Although, the young worms enjoyed normal short-term memories they seemed to lack the ability to share long-term memories. However, the strain of young worms with reduced activity in their insulin-signaling pathways had longer short-term memories that lasted about six hours, or three times as long as in normal worms. While, in case of long-term memory loss lasted for longer than the 40 hours in normal worms.

The mutants also, claimed to have a better learning ability than normal worms. Still, their ability to form long-term memories faded at the same rate as in normal worms. By examining the molecular mechanisms in the worms, scientists analyzed that; a decline in long-term memory may be reported to be linked to a protein named CREB. Researchers further enlightened that, this protein binds DNA and regulates the expression of genes. The protein may also be of vital importance, in the formation of long-term memories in C. elegans, but not required for learning or short-term memory.

Murphy said, “I’m optimistic because we know these longevity mechanisms in C. elegans are conserved in higher organisms, and there are reasons to believe that they could have similar effects on lifespan and cognitive function in humans. But these results also suggest that not every way of extending lifespan is good for cognitive function, which has huge implications for the development of therapies to maintain memory.”

This experiment displays the various factors that extend longevity affect cognitive function in numerous different ways. It also highlights the merits and demerits of effects, over the lifetime of an organism. Further, research intends to determine, the genetic underpinnings of learning, memory, and age-related cognitive decline in C. elegans. For this research, the investigators will be using DNA microarray technology.

The research was published in the May 18 edition of the journal Public Library of Science Biology.