{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:26:55Z","timestamp":1790864815356,"version":"4.1.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIA R21-AG062985"],"award-info":[{"award-number":["NIA R21-AG062985"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Mice with genetic growth hormone (GH) deficiency or GH resistance live much longer than their normal siblings maintained under identical conditions with unlimited access to food. Extended longevity of these mutants is associated with extension of their healthspan (period of life free of disability and disease) and with delayed and\/or slower aging. Importantly, GH and GH-related traits have been linked to the regulation of aging and longevity also in mice that have not been genetically altered and in other mammalian species including humans. Avai+lable evidence indicates that the impact of suppressed GH signaling on aging is mediated by multiple interacting mechanisms and involves trade-offs among growth, reproduction, and longevity. Life history traits of long-lived GH-related mutants include slow postnatal growth, delayed sexual maturation, and reduced fecundity (smaller litter size and increased intervals between the litters). These traits are consistent with a slower pace-of-life, a well-documented characteristic of species of wild animals that are long-lived in their natural environment. Apparently, slower pace-of-life (or at least some of its features) is associated with extended longevity both within and between species. This association is unexpected and may appear counterintuitive, because the relationships between adult body size (a GH-dependent trait) and longevity within and between species are opposite rather than similar. Studies of energy metabolism and nutrient-dependent signaling pathways at different stages of the life course will be needed to elucidate mechanisms of these relationships.<\/jats:p>","DOI":"10.3389\/fendo.2022.916139","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T07:03:41Z","timestamp":1657782221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Somatotropic Axis, Pace of Life and Aging"],"prefix":"10.3389","volume":"13","author":[{"given":"Andrzej","family":"Bartke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"B1","first-page":"1","article-title":"United States Life Tables, 2010","volume":"63","author":"Arias","year":"2014","journal-title":"Natl Vital Stat Rep"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1474-9728.2002.00006.x","article-title":"Big Mice Die Young: Early Life Body Weight Predicts Longevity in Genetically Heterogeneous Mice","volume":"1","author":"Miller","year":"2002","journal-title":"Aging Cell"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111158898","article-title":"Lifespan Extension and Delayed Immune and Collagen Aging in Mutant Mice With Defects in Growth Hormone Production","volume":"98","author":"Flurkey","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"B4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/384033a0","article-title":"Dwarf Mice and the Aging Process","volume":"384","author":"Brown-Borg","year":"1996","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.21.2591","article-title":"Thyroid Status, Disability and Cognitive Function, and Survival in Old Age","volume":"292","author":"Gussekloo","year":"2004","journal-title":"JAMA"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/60.11.1369","article-title":"The Naked Mole-Rat: A New Long-Living Model for Human Aging Research","volume":"60","author":"Buffenstein","year":"2005","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1023\/B:BGEN.0000038022.65024.d8","article-title":"Ageing Studies on Bats: A Review","volume":"5","author":"Brunet-Rossinni","year":"2004","journal-title":"Biogerontology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00006.2012","article-title":"Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity","volume":"93","author":"Bartke","year":"2013","journal-title":"Physiol Rev"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2006.06.005","article-title":"Statistical Analysis Regarding the Effects of Height and Weight on Life Span of the Domestic Dog","volume":"82","author":"Greer","year":"2007","journal-title":"Res Vet Sci"},{"key":"B10","volume-title":"The Retardation of Aging and Disease by Dietary Restriction","author":"Weindruch","year":"1988"},{"key":"B11","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1093\/gerona\/glq178","article-title":"Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice","volume":"66","author":"Miller","year":"2011","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12898","article-title":"Acarbose Improves Health and Lifespan in Aging HET3 Mice","volume":"18","author":"Harrison","year":"2019","journal-title":"Aging Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13328","article-title":"17-a-Estradiol Late in Life Extends Lifespan in Aging UM-HET3 Male Mice; 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