Natural senolytic activity of Rhodiola rosea extract alleviates age-associated phenotypes via paraptosis

  • iScience. 2026 Apr 4;29(5):115607. doi: 10.1016/j.isci.2026.115607.
Ryo Furuuchi  1  2 ,  Yohko Yoshida  2  3 ,  Goro Katsuumi  3  4 ,  Takaaki Furihata  3 ,  Yusuke Joki  3 ,  Chieh-Lun Hsiao  3 ,  Masayoshi Suda  3 ,  Hana Saito  5 ,  Tamano Kumazaki  5 ,  Hidefumi Makabe  5 ,  Manabu Abe  6 ,  Ippei Shimizu  7  8 ,  Tohru Minamino  3
Affiliations
  • 1. Advanced Research Institutes, Bourbon Corporation, Niigata 956-0841, Japan.
  • 2. Department of Advanced Senotherapeutics, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8431, Japan.
  • 3. Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8431, Japan.
  • 4. Department of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
  • 5. Department of Agriculture, Graduate School of Science and Technology, Shinshu University, Kami-ina, Nagano 399-4598, Japan.
  • 6. Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata 951-8510, Japan.
  • 7. Department of Cardiovascular Aging, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 564-8565, Japan.
  • 8. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka 564-8565, Japan.
PMID: 42028013 DOI: 10.1016/j.isci.2026.115607
Abstract

The accumulation of senescent cells drives age-related diseases, and their removal (senolysis) has been reported to ameliorate pathological aging phenotypes. Here, we identified Rhodiola rosea extract (Rosea) as a senolytic agent through screening of edible natural products. In mice, Rosea eliminated irradiation-induced senescent cells and reduced the burden of senescent cells in adipose tissue during obesity, as well as in adipose tissue, skin, and skeletal muscle during aging. These effects were accompanied by improvements in metabolic abnormalities, physical function, skin abnormalities, and behavioral impairments. We further identified oligomers of epigallocatechin (EGC) and epigallocatechin gallate (EGCG), specifically EGC-EGCG and EGCG-EGCG, as the senolytic components. EGC-EGCG targeted vulnerabilities in calcium dynamics between the endoplasmic reticulum and mitochondria in senescent cells, thereby inducing paraptosis-like cell death. These findings suggest that Rosea, containing EGC-EGCG and EGCG-EGCG, represents a natural senolytic candidate capable of delaying, mitigating, or preventing the progression of age-related pathologies.

Keywords
Biological sciences; Molecular biology; Pharmacology.
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