There is a lot of evidence that cancer can cause and is associated with accelerated aging. Agents that are anti aging can also be simultaneously anti cancer.
In recent years, the understanding of cellular senescence has advanced significantly, shedding light on its hallmark features such as cell cycle arrest, resistance to apoptosis, and the development of a senescence-associated secretory phenotype (SASP). As these senescent cells accumulate in aging individuals, they contribute to a range of age-related diseases, leading to poor health, frailty, and increased mortality.
Researchers have been exploring the potential of targeting senescent cells with senolytics or senomorphics to mitigate age-related disorders. These therapies could revolutionize the treatment of various conditions, including neurodegenerative, cardiovascular, metabolic, musculoskeletal, liver, lung, and kidney diseases. However, the primary challenge in developing these therapies lies in finding anti-aging agents with robust safety profiles, a limitation that has hindered many pharmacological advancements.
A significant breakthrough came from Prof. Sun Yu and his team at the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences. They conducted an extensive screening of a natural medicinal agent library, identifying several promising senotherapeutic candidates. Their study, published in Aging Cell on July 20, 2023, highlighted Rutin as a potent senomorphic agent.
Rutin, a phytochemical found in various plants, demonstrated remarkable efficacy in targeting senescent cells. It works by reducing the expression of a broad spectrum of SASP factors. Further investigation revealed that Rutin primarily mitigates the acute stress-associated phenotype (ASAP) by disrupting the interactions between ATM and HIF1α, and ATM and TRAF6. These interactions are crucial in the development of ASAP, which eventually leads to the formation of SASP.
By modulating these pathways, Rutin effectively reduces the pro-inflammatory extracellular environment created by senescent cells, which is often responsible for the onset and worsening of many age-related diseases.
Preclinical data from Sun’s lab indicated that Rutin could significantly enhance the outcomes of chemotherapy, such as mitoxantrone treatment. While cancer cells may become senescent in response to chemotherapy and are unable to proliferate, stromal cells tend to become senescent and help surviving cancer cells resist treatment. Thus, senolytics and senomorphics are being considered as adjunct therapies to eliminate senescent cells during cancer treatment. As effective SASP inhibitors, senomorphics like Rutin preserve the pro-immunogenic capacity of senescent cells, aiding tumor immunosurveillance without the detrimental effects of SASP.
This study offers proof of concept for Rutin as a natural senomorphic agent and an effective treatment modality for age-related diseases, including various cancers. “We hope that our study opens a new window, through which people are able to envision the possibility of discovering more antiaging drugs of natural origin, particularly from plant species, and make informed decisions about their lifespan-extending regimens,” said Dr. Sun.
As research continues, the potential for natural compounds like Rutin to combat aging and improve healthspan becomes increasingly promising, heralding a new era in the fight against age-related diseases.
Reference: Hanxin Liu, Qixia Xu, Halidan Wufuer, Zi Li, Rong Sun, Zhirui Jiang, Xuefeng Dou, Qiang Fu, Judith Campisi, Yu Sun (20 July 2023). Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy. Aging Cell, 23(1). https://doi.org/10.1111/acel.13921
