NMN anti-aging principle popular science, Can activate longevity genes extend our life?

Researchers in China report that activating OSER1, a gene associated with human lifespan, can extend the lifespan of multiple animal models of aging.

Abstract:

• ● Increasing OSER1 gene activity can extend the life span of silkworms, nematodes and flies.
• ● Although the function of OSER1 is still largely unknown, researchers have shown that it can fight cellular stress, which may extend lifespan.
• ● Mutations in this gene have been linked to longer lifespans in humans.

Research published in Nature Communications by Dai and colleagues from Southwest University in China shows that increasing the activation of the gene OSER1, along with increasing the protein it produces, can significantly extend the lifespan of silkworms, nematodes and flies.

What's more, humans also have the OSER1 gene.

These interesting findings may give us insight into potential target genes for gene therapy, which could potentially extend life in the future.

Dr. Lene Juel Rasmussen, one of the authors of the study, said in a press release, "We found this protein that can extend life.

It's a new longevity booster that's found in a variety of animals, such as flies, nematodes, silkworms, and humans." .

1. Longevity protein FOXO activates OSER1 gene

The process of identifying OSER1 begins by examining genes affected by a protein called FOXO.

Because FOXO is closely related to aging regulation, Dai and colleagues believe that some genes activated by FOXO may play a role in longevity.

To find out which genes were activated by FOXO, the researchers used silkworm cells by increasing and decreasing FOXO expression in these cells in order to better identify several silkworm genes that were activated by FOXO.

For example, out of a total of 14,623 genes, 3,185 showed increased activation associated with elevated FOXO.

Further genetic analysis showed that nine of the silkworm genes to which FOXO binds are also present in human genes.

The researchers manipulated the nine identified genes that are also present in human genes, including the OSER1 nematode gene, to measure their effects on lifespan in a variety of aging animal models.

The important conclusion was that in these genes, reducing OSER1 activation shortened life expectancy by about 17%.

Based on this finding, the China-based researchers again conducted a more in-depth analysis of OSER1.

The analysis showed that OSER1 activation increased and decreased in the genetically manipulated silkworms, nematodes and flies, and their lifespan was prolonged and shortened, respectively.

These results suggest that OSER1 strongly influences the lifespan of multiple species, with increasing and decreasing its activity extending or shortening lifespan, respectively.

Multiple species that have been genetically engineered to increase gene activation have shown longer lifespan. In nematodes (Ceoser1-OE), silkworms (BmOSER1-OE), and fruit flies (DmOser1-OE), increased OSER1 gene activation (called overexpression, indicated by dashed lines) extended survival time.

Because FOXO protein stimulates the body's production of an enzyme that can relieve cellular stress on harmful molecules called reactive oxygen species (ROS), Dai and colleagues sought to find out whether a gene activated by FOXO, OSER1, also plays a role in ROS.

They also specifically treated fruit flies with a compound called paraquat, which triggers ROS synthesis and induces cellular stress.

As expected, fruit flies under cellular stress caused by paraquat had a shorter lifespan, but those with higher OSER1 activation after paraquat stress had a partial recovery in lifespan.

These data suggest that boosting OSER1 activation may extend lifespan by reducing cellular stress to ROS.

Increased gene activation under paraquat-induced cellular stress, known as oxidative stress, extended the lifespan of both male and female flies. Compared with male flies treated with paraquat but with no increased OSER1 activity (blue solid line), male flies treated with paraquat and with increased OSER1 activity (blue dashed line) had an average lifespan of nearly 50% longer. Compared with female flies treated with paraquat but with increased OSER1 activity (pink dashed line), the lifespan of female flies treated with paraquat but with increased OSER1 activity increased by nearly 100%.

Dai and colleagues analyzed human data to look at the prevalence of certain mutations in OSER1 in long-lived individuals (those living at least 96 years).

Interestingly, seven point mutations in DNA (called small nucleotide polymorphisms [SNPS] in the OSER1 gene) were associated with a longer life span.

This finding suggests that OSER1 affects longevity not only in multiple animal species, but possibly in humans as well.

2. Development of OSER1 longevity promoting drugs/gene therapy

The findings of Dai and colleagues suggest that scientists may be able to develop therapies that target the OSER1 gene to extend human lifespan.

The treatment could be as simple as gene therapy, boosting the production of the OSER1 protein by increasing mRNA in cells.

Studies in organisms such as mice and non-human primates need to take place before human clinical trials to test the safety and effectiveness of this gene therapy.

Because little is known about the function of the OSER1 gene and its protein, it may trigger cancer by increasing its abundance in multiple tissues throughout the body.

More research is needed to reveal its function before it can be determined whether targeting OSER1 with gene therapy can extend human life.

This may also help reveal whether increasing OSER1 in only certain tissues, such as the kidneys or liver, has a more favorable effect than generally increasing the substance in most tissues throughout the body.

It is worth mentioning here that it is possible for pharmaceutical companies to develop a drug that increases the activity of the OSER1 gene.

Because gene therapy can carry dangers, such as the aforementioned possibility of increasing cancer risk, drugs can be a better tool for enhancing OSER1 activation.

In essence, the discovery of OSER1 as a potential genetic target for extending human lifespan is just the tip of the iceberg.

In this regard, it could take decades to do the research necessary to create gene therapies, or to increase their expression through OSER1 drugs.

In addition, researchers continue to make progress in finding aging interventions, and the real way to combat aging will most likely come from genetic research.

"We are currently focused on uncovering the role of OSER1 in humans, but the lack of existing literature presents a challenge as very little has been published on this topic to date."

This study is the first to demonstrate that OSER1 is an important regulator of aging and longevity.

In the future, we hope to provide insights into specific age-related diseases and aging processes affected by OSER1, "said Zhiquan Li, an author of the study.