TY - JOUR
T1 - S-adenosyl-L-homocysteine extends lifespan through methionine restriction effects
AU - Ogawa, Takafumi
AU - Masumura, Koji
AU - Kohara, Yuki
AU - Kanai, Muneyoshi
AU - Soga, Tomoyoshi
AU - Ohya, Yoshikazu
AU - Blackwell, T. Keith
AU - Mizunuma, Masaki
N1 - Funding Information:
We thank Takeshi Noda and the National BioResource Project/Yeast Genetic Resource Center, Japan, for plasmid and yeast strain. We are grateful to Kaori Igarashi, Ayano Ueno, Maki Ohishi, Ikuko Fukuba, Eri Sanda, Maiko Baba, Feimei Zhu, Juliane Campos, and Laura Paulette Fernandez Cardenas for helpful technical assistance and advice. We also thank Dai Hirata, Kazunori Kume and Makoto Horikawa for helpful discussion. M.M. is supported by the PRIME from Japan Agency for Medical Research and Development JP21gm6110029, JSPS KAKENHI Scientific Research (B) 16H04898, a Challenging Exploratory Research grant 19K22285, Ohsumi Frontier Science Foundation, and Takeda Science Foundation, T.O. and M.M. by the Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers (S2902), and T.K.B by NIH grants GM122610 and AG54215. T.O. is the recipient of a JSPS Overseas Research Fellowships. K.M. is the recipient of the Research Fellowship of the JSPS for Young Scientists (DC1). Generous support from the "Distinguished Researchers" program of Hiroshima University and HiHA are gratefully acknowledged.
Publisher Copyright:
© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
PY - 2022/5
Y1 - 2022/5
N2 - Methionine restriction (MetR) can extend lifespan and delay the onset of aging-associated pathologies in most model organisms. Previously, we showed that supplementation with the metabolite S-adenosyl-L-homocysteine (SAH) extends lifespan and activates the energy sensor AMP-activated protein kinase (AMPK) in the budding yeast Saccharomyces cerevisiae. However, the mechanism involved and whether SAH can extend metazoan lifespan have remained unknown. Here, we show that SAH supplementation reduces Met levels and recapitulates many physiological and molecular effects of MetR. In yeast, SAH supplementation leads to inhibition of the target of rapamycin complex 1 (TORC1) and activation of autophagy. Furthermore, in Caenorhabditis elegans SAH treatment extends lifespan by activating AMPK and providing benefits of MetR. Therefore, we propose that SAH can be used as an intervention to lower intracellular Met and confer benefits of MetR.
AB - Methionine restriction (MetR) can extend lifespan and delay the onset of aging-associated pathologies in most model organisms. Previously, we showed that supplementation with the metabolite S-adenosyl-L-homocysteine (SAH) extends lifespan and activates the energy sensor AMP-activated protein kinase (AMPK) in the budding yeast Saccharomyces cerevisiae. However, the mechanism involved and whether SAH can extend metazoan lifespan have remained unknown. Here, we show that SAH supplementation reduces Met levels and recapitulates many physiological and molecular effects of MetR. In yeast, SAH supplementation leads to inhibition of the target of rapamycin complex 1 (TORC1) and activation of autophagy. Furthermore, in Caenorhabditis elegans SAH treatment extends lifespan by activating AMPK and providing benefits of MetR. Therefore, we propose that SAH can be used as an intervention to lower intracellular Met and confer benefits of MetR.
KW - Caenorhabditis elegans
KW - S-adenosyl-L-homocysteine (SAH)
KW - S-adenosyl-L-methionine (SAM)
KW - Saccharomyces cerevisiae
KW - methionine restriction (MetR)
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U2 - 10.1111/acel.13604
DO - 10.1111/acel.13604
M3 - Article
C2 - 35388610
AN - SCOPUS:85127574995
SN - 1474-9718
VL - 21
JO - Aging Cell
JF - Aging Cell
IS - 5
M1 - e13604
ER -