Mechanism of lifespan extension by procyanidins in C. elegans

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06618
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Inoue Hideshi 東京薬科大学, 生命科学部, 名誉教授 (20184765)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 抗老化 / ポリフェノール / プロシアニジン / 線虫 / 神経

Outline of Final Research Achievements

The cacao liquor procyanidins (CLPr) were found to extend the lifespan of C. elegans. This effect was observed in the fraction containing tetrameric and higher procyanidins, but not in the fraction containing lower procyanidins. Tetrameric cinnamtannin A2 showed a similar effect. The activity requires the sensory neurons AWC, the interneurons AIB, and proteins involved in signal transduction in the neuronal cells and synaptic transmission. Additionally, expressions of CaMKII and p38 MAP kinase in both neural and non-neural tissues were required. It is important to note that procyanidins with a molecular weight of over 1000 can prolong the lifespan of C. elegans through the nervous system. CLPr also enhances tolerance to osmotic stress, depending on factors shared with lifespan extension. While it is not likely a direct cause, the CLPr-induced lifespan extension and stress tolerance have a mechanistic relevance.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

社会の高齢化が進み，健康寿命を保つことが重要である．線虫C.elegansは老化研究によく使われるモデル生物であり，ポリフェノール類が線虫の寿命を伸ばすという報告は多い．しかし，関与する遺伝子は必ずしも一致せず，さまざまな機構が想定される．この研究では，プロシアニジンが線虫の寿命を延長する際に，神経系を介することを初めて明らかにした．しかも，その作用は四量体以上のプロシアニジンに依存している．高重合度プロシアニジンの人への作用が近年着目されるようになったが，そのメカニズムは不明である．この研究で得た知見が，高重合度プロシアニジンが人の健康にどのように寄与するかの理解へつながることが期待される．