Aging is a complex, multi-stage, and gradual process that occurs throughout life. Over time, the body’s organs and muscles will gradually age, and some diseases also occur with age, including cancer, diabetes, cardiovascular disease, and neurodegenerative diseases.
The cellular stress response, also known as the unfolded protein response, occurs when erroneous “unfolded” proteins build up inside the cell, which can be removed by a stress response These problematic proteins restore cellular balance, thereby reducing cellular damage that occurs with age.
On October 19, 2022, researchers from Nanyang Technological University in Singapore published a title in the journal “Nature Communications” Research paper for “The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans”.
The study found that a high-sugar diet can activate cellular stress responses, promote the clearance of misfolded proteins, and prolong lifespan.
Researchers stress that a high-sugar diet is not recommended for older adults, while a high-sugar diet may help prolong the lifespan of aging C. elegans and paving the way for new treatments to address age-related diseases.
Caenorhabditis elegans, a popular model in aging research because they share a similar genome and many cellular pathways to humans, but they only survive three to three Four weeks, which makes their lifespan changes relatively easy to measure.
In the study, researchers analyzed the stress response that occurs when unfolded proteins accumulate within cells, feeding some C. elegans worms a high-glucose diet at two different life stages , juvenile (ie, the beginning of adulthood, day 1), and old age (post-reproduction age, day 5), and the control group was fed a normal diet throughout.
Study finds that older C. elegans worms fed a high-glucose diet lived 24 days, almost twice as long as young worms fed the same diet (13 days) , while C. elegans on a normal diet survived for 20 days.
Glucose prolongs lifespan of senile worms
Additionally, aged worms on a high-glucose diet were more agile and had more energy-storing cells than C. elegans on a normal diet, suggesting healthier aging .
And in young C. elegans, the researchers monitored the activity of three stress sensors in the unfolded protein response pathway. One of the pressure sensors (IRE1) was significantly more active in young worms than in older worms.
When researchers knocked out the gene encoding IRE1, shutting down the cellular pathway for this stress response, they found that larvae fed a high-sugar diet survived for 25 days, up from 2 times. This suggests that the increased activity of the pressure sensor IRE1, a prolonged unfolded protein response, is responsible for their shortened lifespan.
IRE1 regulates the longevity of animals on a high-sugar diet
The high-glucose diet of older worms stimulated their otherwise sluggish unfolded protein response and turned on certain cellular pathways that not only deal with stress caused by excess glucose, but also Aging-related stress is restored and cellular stability is restored.
By contrast, larvae fed a high-glucose diet caused additional stress in the cells due to overactivation of IRE1, and this continued activation instead caused the cells to start dying.
Based on the results, it is possible to develop a method that reduces the activity of IRE1 while increasing the activity of the other two pressure sensorsDrugs to slow cellular aging, thereby extending lifespan.
Still, instead of recommending a high-sugar diet for older adults, researchers highlight a new mechanism in the aging process and pave the way for new treatments to address age-related diseases the way.
The researchers say this is the first study to link this particular stress response to aging, and more research is needed to properly understand the mechanisms at work.
Thesis link:
https:https://doi.org/10.1038/s41467-022-33630-0
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