Decreasing the intake of calories and tweaking the activity of the hormone insulin are two methods long known to increase lifespan in a wide range of organisms.
In particular, studies have shown that longevity can be extended by reducing activity in the insulin-signaling pathway — a chain of events through which insulin influences numerous biological processes, including metabolism, stress response and development.
Now, a team of Princeton biologists has found the first evidence that these mechanisms also have an impact on cognitive function.
By studying worms, the scientists were able to analyze the effects of caloric restriction and reduced insulin signaling on declines in learning and memory brought on by age. The findings have implications for the development of treatments that simultaneously help people live longer and prevent the devastating losses in memory that so often occur with age. Their results are published in the May 18 edition of the journal Public Library of Science Biology.
“The assumption in the field of longevity research has been that organisms able to live longer will function longer as well,” said 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. “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.”
When Murphy and her colleagues looked at the effects of caloric restriction on cognitive function in C. elegans roundworms, they found that restricting calories impaired long-term memory in early adulthood. But surprisingly, the worms did not suffer further memory reduction with age, suggesting that caloric restriction may guard against memory loss over time.
The scientists also studied worms with genetic mutations that allowed the researchers to assess separately the impact of reducing the activity in the insulin-signaling pathway. In contrast to the worms that were eating less, the worms with reduced insulin signaling demonstrated improved long-term memory performance in early adulthood and maintained learning ability better with age. However, these worms were not protected against age-related declines in long-term memory.
The team also found that molecular mechanisms underlying cognitive function in worms are the same as those previously discovered in higher organisms, including mammals, suggesting that the study has far-reaching implications.
C. elegans has long been used for research on aging and longevity, owing to the worm’s simple nervous system, relatively short lifespan of just two to three weeks, and the fact that the worms experience many signs of aging. This includes reduced motility and muscle deterioration, which are seen in other organisms, including humans. Additionally, scientists conducting extensive work on the worms previously have identified several C. elegans mutants with long lifespans, which provide opportunities to explore the molecular and genetic pathways that allow these mutants to live up to 50 percent longer than normal worms.