Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec;18(6):e13034.
doi: 10.1111/acel.13034. Epub 2019 Aug 28.

Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species

Andrey A Parkhitko  1 , Patrick Jouandin  1 , Stephanie E Mohr  1 , Norbert Perrimon  1   2
Affiliations
Review

Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species

Andrey A Parkhitko et al. Aging Cell. 2019 Dec.

Abstract

Methionine restriction (MetR) extends lifespan across different species and exerts beneficial effects on metabolic health and inflammatory responses. In contrast, certain cancer cells exhibit methionine auxotrophy that can be exploited for therapeutic treatment, as decreasing dietary methionine selectively suppresses tumor growth. Thus, MetR represents an intervention that can extend lifespan with a complementary effect of delaying tumor growth. Beyond its function in protein synthesis, methionine feeds into complex metabolic pathways including the methionine cycle, the transsulfuration pathway, and polyamine biosynthesis. Manipulation of each of these branches extends lifespan; however, the interplay between MetR and these branches during regulation of lifespan is not well understood. In addition, a potential mechanism linking the activity of methionine metabolism and lifespan is regulation of production of the methyl donor S-adenosylmethionine, which, after transferring its methyl group, is converted to S-adenosylhomocysteine. Methylation regulates a wide range of processes, including those thought to be responsible for lifespan extension by MetR. Although the exact mechanisms of lifespan extension by MetR or methionine metabolism reprogramming are unknown, it may act via reducing the rate of translation, modifying gene expression, inducing a hormetic response, modulating autophagy, or inducing mitochondrial function, antioxidant defense, or other metabolic processes. Here, we review the mechanisms of lifespan extension by MetR and different branches of methionine metabolism in different species and the potential for exploiting the regulation of methyltransferases to delay aging.

Keywords: S-adenosylmethionine; aging; lifespan; methionine restriction; methylation; methyltransferases.

PubMed Disclaimer

Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
Schematic of methionine metabolism
Figure 2
Figure 2
Methionine metabolism and methyltransferases
Figure 3
Figure 3
Mechanisms of lifespan extension by methionine metabolism and methyltransferases
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Systems genetics identifies methionine as a high risk factor for Alzheimer's disease.
    Wang C, Hei Y, Liu Y, Bajpai AK, Li Y, Guan Y, Xu F, Yao C. Wang C, et al. Front Neurosci. 2024 Jul 16;18:1381889. doi: 10.3389/fnins.2024.1381889. eCollection 2024. Front Neurosci. 2024. PMID: 39081851 Free PMC article.
  • SAM, SAH and C. elegans longevity: insights from a partial AHCY deficiency model.
    Thapa P, Olek K, Kowalska A, Serwa RA, Pokrzywa W. Thapa P, et al. NPJ Aging. 2023 Dec 5;9(1):27. doi: 10.1038/s41514-023-00125-1. NPJ Aging. 2023. PMID: 38052822 Free PMC article.
  • Biomarkers of aging.
    Aging Biomarker Consortium; Bao H, Cao J, Chen M, Chen M, Chen W, Chen X, Chen Y, Chen Y, Chen Y, Chen Z, Chhetri JK, Ding Y, Feng J, Guo J, Guo M, He C, Jia Y, Jiang H, Jing Y, Li D, Li J, Li J, Liang Q, Liang R, Liu F, Liu X, Liu Z, Luo OJ, Lv J, Ma J, Mao K, Nie J, Qiao X, Sun X, Tang X, Wang J, Wang Q, Wang S, Wang X, Wang Y, Wang Y, Wu R, Xia K, Xiao FH, Xu L, Xu Y, Yan H, Yang L, Yang R, Yang Y, Ying Y, Zhang L, Zhang W, Zhang W, Zhang X, Zhang Z, Zhou M, Zhou R, Zhu Q, Zhu Z, Cao F, Cao Z, Chan P, Chen C, Chen G, Chen HZ, Chen J, Ci W, Ding BS, Ding Q, Gao F, Han JJ, Huang K, Ju Z, Kong QP, Li J, Li J, Li X, Liu B, Liu F, Liu L, Liu Q, Liu Q, Liu X, Liu Y, Luo X, Ma S, Ma X, Mao Z, Nie J, Peng Y, Qu J, Ren J, Ren R, Song M, Songyang Z, Sun YE, Sun Y, Tian M, Wang S, Wang S, Wang X, Wang X, Wang YJ, Wang Y, Wong CCL, Xiang AP, Xiao Y, Xie Z, Xu D, Ye J, Yue R, Zhang C, Zhang H, Zhang L, Zhang W, Zhang Y, Zhang YW, Zhang Z, Zhao T, Zhao Y, Zhu D, Zou W, Pei G, Liu GH. Aging Biomarker Consortium, et al. Sci China Life Sci. 2023 May;66(5):893-1066. doi: 10.1007/s11427-023-2305-0. Epub 2023 Apr 11. Sci China Life Sci. 2023. PMID: 37076725 Free PMC article. Review.
  • A Phase I Trial of a Methionine Restricted Diet with Concurrent Radiation Therapy.
    Mattes MD, Koturbash I, Leung CN, Wen S, Jacobson GM. Mattes MD, et al. Nutr Cancer. 2024;76(6):463-468. doi: 10.1080/01635581.2024.2340784. Epub 2024 Apr 9. Nutr Cancer. 2024. PMID: 38591931 Free PMC article. Clinical Trial.
  • An insulin-sensitive Drosophila insulin-like receptor mutant remodels methionine metabolism to extend lifespan.
    Tatar M, Zheng W, Yadav S, Yamamoto R, Curtis-Joseph N, Li S, Wang L, Parkhitko AA. Tatar M, et al. PLoS Genet. 2025 Jun 16;21(6):e1011640. doi: 10.1371/journal.pgen.1011640. eCollection 2025 Jun. PLoS Genet. 2025. PMID: 40523036 Free PMC article.
See all "Cited by" articles

References

    1. Abe, M. , Naqvi, A. , Hendriks, G. J. , Feltzin, V. , Zhu, Y. , Grigoriev, A. , & Bonini, N. M. (2014). Impact of age‐associated increase in 2'‐O‐methylation of miRNAs on aging and neurodegeneration in Drosophila . Genes & Development, 28, 44–57. 10.1101/gad.226654.113 - DOI - PMC - PubMed
    1. Ables, G. P. , Hens, J. R. , & Nichenametla, S. N. (2016). Methionine restriction beyond life‐span extension. Annals of the New York Academy of Sciences, 1363, 68–79. 10.1111/nyas.13014 - DOI - PubMed
    1. Ables, G. P. , Ouattara, A. , Hampton, T. G. , Cooke, D. , Perodin, F. , Augie, I. , & Orentreich, D. S. (2015). Dietary methionine restriction in mice elicits an adaptive cardiovascular response to hyperhomocysteinemia. Scientific Reports, 5, 8886 10.1038/srep08886 - DOI - PMC - PubMed
    1. Ables, G. P. , Perrone, C. E. , Orentreich, D. , & Orentreich, N. (2012). Methionine‐restricted C57BL/6J mice are resistant to diet‐induced obesity and insulin resistance but have low bone density. PLoS ONE, 7, e51357 10.1371/journal.pone.0051357 - DOI - PMC - PubMed
    1. Agrawal, V. , Alpini, S. E. , Stone, E. M. , Frenkel, E. P. , & Frankel, A. E. (2012). Targeting methionine auxotrophy in cancer: Discovery & exploration. Expert Opinion on Biological Therapy, 12, 53–61. - PubMed

Publication types