Kirin eyes cellular senescence as part of R&D focus

A picture showing dried Agrimonia pilosa.
Kirin Group and its health sciences arm is Agrimonia pilosa, a perennial plant of the rose family, as a candidate for targeting cellular senescence. (Getty Images)

Kirin Group is gearing up research and development efforts targeting factors of aging, including cellular senescence and chronic inflammation.

The company revealed the above during its annual R&D Day held last month.

Predominantly known for its beer brewery business, Kirin also runs a pharmaceutical arm and health science business. It is most established for its immune support postbiotic Lactococcus lactis strain Plasma, also known as LC-plasma.

During a special roundtable discussion titled “Aging Care Research and Its Implementation in Society”, topics such as the 14 Hallmarks of Aging and the XPRIZE competition were raised. In particular, Kirin has set its sights on tackling cellular senescence and chronic inflammation.

It has identified Agrimonia pilosa—a perennial plant of the rose family that grows wild in mountainous and wooded areas and is used as a folk remedy—as a candidate for targeting cellular senescence.

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Commonly known in Japan as “Kinmizuhiki”, Kirin said that the plant was selected from approximately 4,000 materials as an ingredient for supporting brain function.

The company said it first discovered the plant’s ability to remove senescent cells in 2020.

Commercialization in sight...but lack of testing methods

To date, Kirin’s subsidiary FANCL Corporation has developed a Food with Function Claim (FFC) containing Agrimonia pilosa, which is claimed to help maintain positive mood and reduce temporary fatigue.

Marketed as Wellage Premium, the product launched last April.

In addition to the existing claims, Kirin is working to add “anti-aging” to the product’s functional claims; however, it also acknowledged that commercialization of products making such claims would be dependent on the ability to develop a method that measures the number of senescent cells in the body.

This will be a focus this year.

“This year, we’re still working on finding what else we can expect for anti-aging, and we have not yet developed the methodology to measure senescent cells,” the company stated. “So first, we are trying to develop how to measure how much aging this consumer is. By developing this kind of methodology, I think that we can contribute more to our product.”

Research findings on Agrimonia pilosa

A clinical trial conducted on 110 middle-aged Japanese reported that supplementation with Agrimonia pilosa Ledeb. extract could reduce senescent immune cells.

Preliminary data from the trial funded by FANCL were published in Nutrients last February.

The 110 participants between the ages of 40 and 59 were selected from 635 individuals screened for immunosenescence, with a high proportion of high-SA-βGal CD8+ T cells as the selection criteria. These cells are also known as senescent immune cells.

They were randomized to take either 50 mg of the extract containing 0.2 mg of agrimols or the placebo for eight weeks.

The primary endpoint of this study was the change in the proportion of high-SA-βGal CD8+ T cells in human peripheral blood mononuclear cells (PBMCs).

Findings showed that the proportion of high-SA-βGal CD8+ T cells decreased in both the intervention and placebo groups, with no significant differences between groups, by the end of the trial.

Subgroup analysis, however, showed that the proportion of high-SA-βGal CD8+ T cells was significantly lower in men who took the extract as compared to those who took a placebo.

In contrast, females in both groups showed a decrease by the end of the trial, with no significant difference between the groups.

The researchers also studied the proportion of naïve CD8+ T cells and effector memory CD8+ T cells in males and reported that the intervention group had a significantly higher naïve CD8+ T cells but a lower effector memory CD8+ T cells by the end of the study.

Based on this finding, it was suggested that “the increase in the number of naïve T cells was due to the removal of senescent effector memory CD8+ T cells,” the researchers wrote.

As to why no such observations were seen in the female participants, the researchers said this could be due to effects from female hormones like estrogen, which plays a role in modulating the expression of senescence-related proteins and also influencing the differentiation and activation of T cells.

“In this study, the consumption of APE resulted in little change in the proportion of central memory T cells; however, the proportion of effector memory T cells decreased while that of naïve T cells increased,” the researchers concluded. “This suggests that the consumption of APE may eliminate effector memory CD8+ T cells that highly express SA-βGal and are undergoing aging.”

Aspergillus bioactive for chronic inflammation

Another ingredient identified for tackling the hallmarks of aging, specifically chronic inflammation, is Aspergillus extract containing 14-dehydroergosterol (14-DHE).

According to the company, 14-DHE tackles chronic inflammation via the induction of tolerogenic dendritic cells and the induction of regulatory T cells or Tregs.

At the moment, the company has demonstrated the ingredient’s benefits for skin.

Published in March 2018 in Clinical, Cosmetic and Investigational Dermatology, the 12-week study involving 70 women reported that the supplementation of Koji extract containing 14-DHE could improve skin moisture in the stratum corneum.