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While the exact mechanism through which DR acts remains elusive, the gasotransmitter hydrogen sulphide (H<jats:sub>2<\/jats:sub>S) may play an important role. We employed a comparative-type approach using females from three ILSXISS recombinant inbred mouse strains previously reported to show differential lifespan responses following 40% DR. Following long-term (10\u00a0months) 40% DR, strain TejJ89\u2014reported to show lifespan extension under DR\u2014exhibited elevated hepatic H<jats:sub>2<\/jats:sub>S production relative to its strain-specific ad libitum (AL) control. Strain TejJ48 (no reported lifespan effect following 40% DR) exhibited significantly reduced hepatic H<jats:sub>2<\/jats:sub>S production, while H<jats:sub>2<\/jats:sub>S production was unaffected by DR in strain TejJ114 (shortened lifespan reported following 40% DR). These differences in H<jats:sub>2<\/jats:sub>S production were reflected in highly divergent gene and protein expression profiles of the major H<jats:sub>2<\/jats:sub>S production and disposal enzymes across strains. Increased hepatic H<jats:sub>2<\/jats:sub>S production in TejJ89 mice was associated with elevation of the mitochondrial H<jats:sub>2<\/jats:sub>S-producing enzyme 3-mercaptopyruvate sulfurtransferase (MPST). Our findings further support the potential role of H<jats:sub>2<\/jats:sub>S in DR-induced longevity and indicate the presence of genotypic-specificity in the production and disposal of hepatic H<jats:sub>2<\/jats:sub>S in response to 40% DR in mice.<\/jats:p>","DOI":"10.1007\/s11357-020-00168-2","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T10:03:03Z","timestamp":1583920983000},"page":"801-812","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Strain-specificity in the hydrogen sulphide signalling network following dietary restriction in recombinant inbred mice"],"prefix":"10.1007","volume":"42","author":[{"given":"Stephen E.","family":"Wilkie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Mulvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Sands","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana E.","family":"Marcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick N.","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Morton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Hine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8727-0593","authenticated-orcid":false,"given":"Colin","family":"Selman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,11]]},"reference":[{"key":"168_CR1","doi-asserted-by":"publisher","unstructured":"Arndt S,\u00a0Baeza-Garza CD, Logan A, Rosa T, Wedmann R, Prime TA, Martin JL, Saeb-Parsy K, Krieg T, Filipovic, MR, Hartley RC, Murphy MP (2017) Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA. 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