Aging can be delayed by manipulating cellular stress responses

Overview: Switched on at pre-reproductive ages, cellular stress responses may slow aging and extend lifespan.

sauce: NTU

Scientists at Singapore’s Nanyang Technological University (NTU Singapore) have found that stress responses within cells, when “switched on” at post-reproductive age, may be key to slowing aging and extending lifespan. discovered.

In a laboratory on a type of roundworm that shares similarities with humans, a team at NTU Singapore turned on this stress response in aged roundworms by feeding them a high-glucose diet compared to normal-fed roundworms. It has been found that this prolongs life.

This is the first time the link between this stress response and aging has been found, the NTU team said in a study released on October 19. Nature Communications.

While more research is needed to better understand this link, scientists believe their findings could help delay onset and address age-related disorders such as cancer, dementia and stroke. It is said to open the door to the development of therapeutics.

Associate Professor Guillaume Thibault, cell biologist and research director at NTU’s Department of Biological Sciences, 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.

“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.” This study shows that triggering specific stress responses in cells can lead to longevity, and that drug activation of these stress responses is important in slowing cellular aging. There is a possibility.”

Scientists at NTU not only show the effects of manipulating this stress response in aged worms, but when young worms fed a high-glucose diet are “switched off,” the same response makes them live longer than normal worms. We have also shown that it is useful for diet.

As an independent expert, Professor Rong Li, Director of the Institute of Mechanobiology, National University of Singapore, said: The study is influential because scientists have identified a cellular pathway called the denatured protein response that affects lifespan in animals fed a high-glucose diet.

“They found that inhibiting this pathway dramatically extended lifespan in these animals. Therefore, they found that targeting this pathway could extend lifespan in humans with metabolic disorders.” I suggest that it is possible.”

The research is in line with the research pillars of the university’s NTU2025 Five-Year Strategic Plan, which focuses on health and society as one area with the potential for significant intellectual and social impact.

How Cellular Stress Responses Are Activated

Cells generate a stress response when a stressor (such as excess glucose) causes the accumulation of problematic ‘unfolded’ proteins within the cell. The stress response, called the unfolded protein response, works to rid the body of these problematic proteins and restore balance within the cell.

Aging can also lead to the accumulation of unfolded proteins due to the natural decline in the ability of cellular machinery to produce healthy proteins, triggering the same stress response.

Molecular machinery within the cell addresses this accumulation through ‘stress sensors’ that initiate a series of molecular mechanisms to rescue the cell from this stress. If the unfolded protein overload is not resolved, a prolonged unfolded protein response instead induces cell death.

Unfolding protein responses in aged worms led to healthier aging

To investigate how the unfolded protein response affects animal longevity, scientists elicited this response in adult roundworms (Caenorhabditis elegans) Use glucose.in the meantime Nematode Anatomically much simpler than humans, they rely on many of the same genes that humans do to control cell division and program defective cells to die.

Scientists fed several nematodes on high-glucose diets at two different life stages. Larvae, the beginning of the adult stage (day 1), and post-reproductive age (day 5), when the worm is older and no longer. fertile. A control group of nematodes was fed a normal diet throughout.

Scientists found 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.

Aside from longer lifespans, older worms fed a high-glucose diet were more agile and had more energy-storing cells compared to worms fed a normal diet. . This suggests a healthier aging.

Prolonged stress response of young worms led to cell death

One day after feeding the worms a high-glucose diet, NTU scientists monitored the activity of three stress sensors, each involved in a cellular pathway of unfolded protein responses.

They found that one of the stress sensors, IRE1, was significantly more active in young compared to old worms.

When scientists removed the gene encoding IRE1 in worms to ‘switch off’ cellular pathways initiated by stress sensors, they found that young worms fed a high-glucose diet from day one lived for 25 days. Did. The gene was intact.

This suggests that the increased activity of the stress sensor IRE1 (prolonged unfolded protein responses, scientists say) seen in larvae fed a high-glucose diet from day 1 was implicated in shortened lifespan. It suggests that

Associate Professor Thibault said: Restores cell stability.

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“In contrast, larvae fed a high-glucose diet caused unresolved stress in the cell due to overactivation of IRE1. It has started.”

This finding suggests that agents that reduce the activity of IRE1 and increase the activity of two other stress sensors may be developed to slow cellular senescence and, consequently, extend lifespan. There are, he added.

More research and findings need to be conducted on roundworms. We further analyze the complex mechanism behind lifespan extension induced by a high-glucose diet and how this mechanism interacts with other processes in the cell.

Other authors on the study are NTU Research Fellow Dr Cenk Celik and Research Assistant Aishah Tul-Firdaus Abdul Khalid. Former NTU researchers Caroline Beaudoin-Chabot, Wang Lei, Subhash Thalappilly and Xu Shiyi. NTU alumni are Koh Jhee Hong, Venus Lim Wen Xuan and Low Ann Don.

Funding: This work was supported by the Singapore Ministry of Education Academic Research Fund Tier 2 (2018-T2-1-002) and Tier 1 (2019-T1-002-011). Singapore Ministry of Health, National Medical Research Council Open Fund Individual Research Grant (MOH-000566).

About this Aging and Longevity Research News

author: Hu Jane
sauce: NTU
contact: Hu Jane – NTU
image: image is public domain

Original research: open access.
“The unfolded protein response reverses the effects of glucose on the longevity of chemically sterilized foods. NematodeGuillaume Thibaud and others Nature Communications

Overview

The unfolded protein response reverses the effects of glucose on the longevity of chemically sterilized foods. Nematode

Metabolic diseases often share common features such as the accumulation of unfolded proteins in the endoplasmic reticulum (ER). ER stress activates the unfolded protein response (UPR) to limit cellular damage that diminishes with age.

here, Caenorhabditis elegans Persons fed a high-glucose-supplemented bacterial diet on day 5 of adulthood (HGD-5) have increased lifespan, whereas those exposed on day 1 (HGD-1) have reduced lifespan .

A metabolic shift was observed only in HGD-1, whereas glucose and infertility synergistically extended the lifespan of HGD-5 independently of DAF-16. In particular, we identified that the UPR stress sensors ATF-6 and PEK-1 contributed to the lifespan of her HGD-5 worms. IRE-1 Ablation significantly extended the lifespan of HGD-1.

Together, we hypothesize that HGD activates the quiescent UPR in aged C. elegans to overcome senescence-associated stress and restore ER homeostasis. In contrast, young animals subjected to HGD cause unresolved ER stress, which in turn triggers detrimental stress responses.