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조회379

GIST, 현 건국대학교

Nat. Commun., 30 December 2024 | https://doi.org/10.1038/s41467-024-55015-1 A microbiota-derived metabolite, 3-phenyllactic acid, prolongs healthspan by enhancing mitochondrial function and stress resilience via SKN-1/ATFS-1 in C. elegans

Juewon Kim^1,2,8, Yunju Jo^1,8, Gyumin Lim³, Yosep Ji⁴, Jong-Hwa Roh⁵, Wan-Gi Kim⁵, Hyon-Seung Yi^6,7, Dong Wook Choi³, Donghyun Cho^4,5 & Dongryeol Ryu¹

¹Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
²Department of Physiology, Konkuk University College of Medicine, Chungju, Republic of Korea.
³Department of Biotechnology, College of Life Sciences and Biotechnology Korea University Seoul, Seoul, Republic of Korea.
⁴HEM Pharma Inc., 407, Suwon, Republic of Korea.
⁵Amorepacific Research & Innovation Center, Yongin, Republic of Korea.
⁶Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
⁷Department of Medical Science, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
⁸These authors contributed equally: Juewon Kim, Yunju Jo.

Corresponding authors
Correspondence to Hyon-Seung Yi, Dong Wook Choi, Donghyun Cho or Dongryeol Ryu.

Abstract

The mechanisms underlying the impact of probiotic supplementation on health remain largely elusive. While previous studies primarily focus on the discovery of novel bioactive bacteria and alterations in the microbiome environment to explain potential probiotic effects, our research delves into the role of living Lactiplantibacillus (formerly known as Lactobacillus) and their conditioned media, highlighting that only the former, not dead bacteria, enhance the healthspan of Caenorhabditis elegans (C. elegans). To elucidate the underlying mechanisms, we conduct transcriptomic profiling through RNA-seq analysis in C. elegans exposed to GTB1, a strain of Lactiplantibacillus plantarum or 3-phenyllactic acid (PLA), mimicking the presence of key candidate metabolites of GTB1 and evaluating healthspan. Our findings reveal that PLA treatment significantly extends the healthspan of C. elegans by promoting energy metabolism and stress resilience in a SKN-1/ATFS-1-dependent manner. Moreover, PLA-mediated longevity is associated with a novel age-related parameter, the Healthy Aging Index (HAI), introduced in this study, which comprises healthspan-related factors such as motility, oxygen consumption rate (OCR), and ATP levels. Extending the relevance of our work to humans, we observe an inverse correlation between blood PLA levels and physical performance in patients with sarcopenia, when compared to age-matched non-sarcopenic controls. Our investigation thus sheds light on the pivotal role of the metabolite PLA in probiotics-mediated enhancement of organismal healthspan, and also hints at its potential involvement in age-associated sarcopenia. These findings warrant further investigation to delineate PLA’s role in mitigating age-related declines in healthspan and resilience to external stressors.

논문정보

형식Research article
게재일2024년 12월 (BRIC 등록일 2024-12-31)
연구진국내 연구진
분야 생명과학 > 노화/암생물학

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