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Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype.

Publication ,  Journal Article
Liang, Y; Pan, C; Yin, T; Wang, L; Gao, X; Wang, E; Quang, H; Huang, D; Tan, L; Xiang, K; Wang, Y; Alexander, PB; Li, Q-J; Yao, T-P ...
Published in: Adv Sci (Weinh)
January 2024

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence-associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation-related diseases. Altered BCAA metabolism driving the SASP is mediated by robust activation of the BCAA transporters Solute Carrier Family 6 Members 14 and 15 as well as downregulation of the catabolic enzyme BCAA transaminase 1 during onset of cellular senescence, leading to highly elevated intracellular BCAA levels in senescent cells. This, in turn, activates the mammalian target of rapamycin complex 1 (mTORC1) to establish the full SASP program. Transgenic Drosophila models further indicate that orthologous BCAA regulators are involved in the induction of cellular senescence and age-related phenotypes in flies, suggesting evolutionary conservation of this metabolic pathway during aging. Finally, experimentally blocking BCAA accumulation attenuates the inflammatory response in a mouse senescence model, highlighting the therapeutic potential of modulating BCAA metabolism for the treatment of age-related and inflammatory diseases.

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Published In

Adv Sci (Weinh)

DOI

EISSN

2198-3844

Publication Date

January 2024

Volume

11

Issue

2

Start / End Page

e2303489

Location

Germany

Related Subject Headings

  • Senescence-Associated Secretory Phenotype
  • Mice
  • Mechanistic Target of Rapamycin Complex 1
  • Mammals
  • Leucine
  • Energy Metabolism
  • Animals
  • Amino Acids, Branched-Chain
 

Citation

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ICMJE
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Liang, Y., Pan, C., Yin, T., Wang, L., Gao, X., Wang, E., … Wang, X.-F. (2024). Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype. Adv Sci (Weinh), 11(2), e2303489. https://doi.org/10.1002/advs.202303489
Liang, Yaosi, Christopher Pan, Tao Yin, Lu Wang, Xia Gao, Ergang Wang, Holly Quang, et al. “Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype.Adv Sci (Weinh) 11, no. 2 (January 2024): e2303489. https://doi.org/10.1002/advs.202303489.
Liang Y, Pan C, Yin T, Wang L, Gao X, Wang E, et al. Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype. Adv Sci (Weinh). 2024 Jan;11(2):e2303489.
Liang, Yaosi, et al. “Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype.Adv Sci (Weinh), vol. 11, no. 2, Jan. 2024, p. e2303489. Pubmed, doi:10.1002/advs.202303489.
Liang Y, Pan C, Yin T, Wang L, Gao X, Wang E, Quang H, Huang D, Tan L, Xiang K, Wang Y, Alexander PB, Li Q-J, Yao T-P, Zhang Z, Wang X-F. Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype. Adv Sci (Weinh). 2024 Jan;11(2):e2303489.
Journal cover image

Published In

Adv Sci (Weinh)

DOI

EISSN

2198-3844

Publication Date

January 2024

Volume

11

Issue

2

Start / End Page

e2303489

Location

Germany

Related Subject Headings

  • Senescence-Associated Secretory Phenotype
  • Mice
  • Mechanistic Target of Rapamycin Complex 1
  • Mammals
  • Leucine
  • Energy Metabolism
  • Animals
  • Amino Acids, Branched-Chain