• Ginger extract selectively caused the death of senescent cells without affecting proliferating cells.
  • Among the ginger extract components, gingerenone A showed promising senolytic properties and selectively eliminated cultured human senescent cells.
  • Gingerenone A was more selective at eliminating senescent cells than a known and popular senolytic cocktail, dasatinib and quercetin.

In animals, eliminating senescent cells – zombie-like cells that stop growing and replicating with age – improves healthspan and slows down the development of aging characteristics associated with functional impairment. For example, clearing senescent cells through genetic engineering in mice improved age-associated disorders, such as atherosclerosis, neurodegeneration, sarcopenia, cataracts, cardiac hypertrophy, kidney disease, cancer, and osteoarthritis. So, the clearance of senescent cells by drugs (senotherapeutics) provides a promising avenue to combat age-related disorders and functional impairments.

Researchers from the National Institute on Aging (NIA) in Baltimore show that a compound from ginger extract called gingerenone A is a promising therapeutic. As inflammation is a hallmark of senescence, Moaddel and colleagues tested four plant extracts with known anti-inflammatory effects, among which, ginger extract displayed robust senolytic activity. Gingerenone A and 6-shogaol were identified as active components in ginger extract, with gingerenone A showing higher selectivity for eliminating senescent cells compared to a known senolytic cocktail, dasatinib plus quercetin. The research was published in the journal PLoS One on March 29, 2022.

Searching for Natural Senotherapeutics

Senotherapeutics include senolytic drugs, which selectively eliminate senescent cells by inducing cell death, and senomorphics, which can either suppress the secretion of senescence-inducing compounds or repress senescence without killing off the cells. To date, very few senotherapeutic compounds have been identified and validated, including navitoclax, fisetin, piperlongumine, and the senolytic cocktail dasatinib and quercetin (D+Q). More recently, extracts from plants like the perennial herb Solidago alpestris and the Antarctic hair grass Deschampsia antartica displayed senolytic activity. However, the active components in these plant extracts have not been isolated or characterized.

Gingerenone A Has Strong Senotherapeutic Potential

Researchers from the NIA have previously shown that screening plant extracts is a viable approach for identifying bio-active compounds with potential therapeutic properties. This team proposed that plant extracts with known anti-inflammatory effects may contain active compounds with senolytic or senomorphic properties.

To this end, Moaddel and colleagues from the NIA screened extracts from four plants with well-established anti-inflammatory properties, including extracts from Harpagophytum procumbens (Devil’s Claw), Uncaria tomentosa (Cat’s Claw), Zingiber officinale Rosc. (ginger) and Solidago canadensis (Canadian Goldenrod). The extract from Zingiber officinale Rosc. (ginger) was found to reduce both senescent cell viability and the presence of indicators of senescence.

When screening the ginger extract, Moaddel and colleagues whittled down the list to two active compounds: gingerenone A and 6-shogaol. Gingerenone A was the most promising component identified in ginger extract since it reduced senescent cell viability, enhanced the levels of cell death markers, and had strong senomorphic activity, reducing the production of SASP related compounds. Interestingly, while 6-shogaol is known to have strong anti-inflammatory properties, it did not display senomorphic effects in the study.

(Moaddel et al., 2022 | PLoS One) Gingerenone A and 6-shogaol have senolytic effects. Human fibroblasts were either left untreated (proliferating, grey) or exposed to ionizing radiation (senescent, red) and cultured for an additional ten days. These cells were then treated for 2 days with a catalog of compounds. The data shows that gingerenone A has stronger senolytic activity than dasatinib plus quercetin (D+Q) and the other ginger extract candidate 6-Shogaol. Moreover, gingerenone A was more selective at eliminating senescence cells, as shown by the lack of elimination of non-senescent, proliferating cells, which was not the case for D+Q.

“Together, our findings suggest that gingerenone A suppresses several senescence traits and promotes senolysis, thus representing a promising natural senolytic compound,” said Moaddel and colleagues from the NIA. Additional investigation is needed to fully characterize the detailed mechanism of its senolytic or senomorphic effects. This study further reveals a screening method suitable for identifying plant extracts and their active components with senolytic activity in culture. Further studies are needed to demonstrate senotherapeutic activity in live animals before moving into human studies.