Cellular stress in aging worms leads to healthier aging

While young worms respond to cellular stress with shorter lifespans, similar stresses prolong survival in older worms, reports scientists at Singapore’s Nanyang Technological University (NTU). research paper of Nature CommunicationsAlthough the study was done in roundworms (Caenorhabditis elegans), these anatomically simple organisms rely on many of the same genes that humans do to control cell division and cell death. It may open new avenues of research into treatments for the associated disorders.

Dr. Guillaume Thibault, cell biologist and associate professor at NTU, lead author of the study, said: From a public health perspective, identifying the cellular pathways that underpin the aging process can bring us one step closer to developing new therapeutic strategies to treat age-related disorders. “

A pivotal metabolic mechanism called the unfolded protein response (UPR) that limits cellular damage in response to stress is impaired in many metabolic and age-related diseases, resulting in the accumulation of unfolded proteins in the endoplasmic reticulum (ER). . The current study shows that activating the UPR stress response pathway in aging post-reproductive worm cells slows aging and extends lifespan.

To investigate the effects of UPR activation on longevity, scientists used high levels of glucose as a stressor to induce the pathway. They showed that aged worms fed a high-glucose diet lived longer than worms fed a normal diet.

“Our study found that a high-glucose diet may help slow aging and extend the lifespan of aged worms, but we do not recommend that older adults switch to a high-sugar diet.” Hmm.. “This study shows that triggering specific stress responses in cells can lead to longevity, and that drug activation of these stress responses is important for slowing cellular aging. It means it is possible.”

Scientists observed that old worms fed a high-glucose diet lived for 24 days. This is almost double the lifespan (13 days) of young worms fed the same diet. Worms on regular diet lived for 20 days. In addition to having a longer lifespan, aged worms fed a high-glucose diet were more agile and had more energy-storing cells compared to worms fed a normal diet. It was suggested that they aged more healthily.

After a day of feeding young and old worms on a high-glucose diet, scientists monitored the activity of three stress sensors. Each is involved in her UPR pathway in the cell. They noted that her one of the sensors, her IRE1, was much more active in young compared to old worms.

When scientists “switched off” the cellular pathway by deleting IRE1, the larvae were fed a high-glucose diet from day one and found to survive for 25 days, twice as long as when the IRE1 gene was intact. This suggests that increased her IRE1 activity in larvae fed a high-glucose diet is responsible for the shortened lifespan.

The authors also showed that the UPR stress sensor genes ATF-6 and PEK-1 contribute to lifespan in old C. elegans.

“The high-glucose diet fed to aging worms stimulates an otherwise slow unfolding protein response, switching on specific cellular pathways, not only the stress induced by excess glucose, but also other aging worms. I believe that it also addressed the stress associated with cellulite and restored cellular stability,” said Thibaud.. “In contrast, larvae fed a high-glucose diet caused unresolved stress in the cell due to overactivation of IRE1. It has started.”

The findings indicate that therapeutically reducing IRE1 activity while increasing activity of two other stress sensors may delay aging and extend lifespan.

“Metabolic diseases, if left untreated, have serious consequences in the elderly. Scientists have identified a cellular pathway called the denatured protein response that affects lifespan in animals fed a high-glucose diet.” This study is influential because they found that inhibiting this pathway dramatically extended the lifespan of these animals. It has the potential to extend the lifespan of disabled humans,” said Dr. Rong Li, professor and director of NTU’s Institute of Mechanobiology, who was not involved in the study. Hmm.