Sirtuins, Aging, and Medicine
Sirtuins were originally identified as antiaging proteins in model genetic organisms and have emerged as mediators of the beneficial effects of calorie restriction in mammals. The mammalian Sir2 orthologue, SIRT1, is an NAD-dependent deacetylase that is involved in many central pathways governing ph...
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| Format: | Article |
| Language: | English |
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Massachusetts Medical Society
2020
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| Online Access: | https://hdl.handle.net/1721.1/124934 |
| _version_ | 1811089617224466432 |
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| author | Guarente, Leonard Pershing |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Guarente, Leonard Pershing |
| author_sort | Guarente, Leonard Pershing |
| collection | MIT |
| description | Sirtuins were originally identified as antiaging proteins in model genetic organisms and have emerged as mediators of the beneficial effects of calorie restriction in mammals. The mammalian Sir2 orthologue, SIRT1, is an NAD-dependent deacetylase that is involved in many central pathways governing physiology and stress management. Genetic or pharmacologic activation of SIRT1 can benefit numerous diseases in murine models. Indeed, two different SIRT1-activating compounds are now in a diverse set of phase 1 or phase 2 human trials (ClinicalTrials.gov numbers, NCT00937326, NCT00964340, NCT01014117, NCT01018017, NCT01018628, NCT01262911, NCT01031108, and NCT01154101). Beyond SIRT1, there are six other mammalian sirtuins (SIRT2, 3, 4, 5, 6, and 7), and all may turn out to have therapeutic potential with the use of activators or inhibitors. Among these sirtuins, SIRT3 is extremely interesting, because it appears to suppress one of the contributing causes of aging itself, reactive oxygen species in mitochondria. Indeed, genetic polymorphisms in the SIRT3 promoter have been associated with extreme longevity in an Italian population,89,90 although these studies will have to be replicated in other groups. In conclusion, sirtuins are a unique class of proteins that link protein acetylation to metabolism and exert profound effects on mammalian physiology and diseases of aging. The development of drugs that target sirtuins to treat these diseases is ongoing. |
| first_indexed | 2024-09-23T14:22:02Z |
| format | Article |
| id | mit-1721.1/124934 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:22:02Z |
| publishDate | 2020 |
| publisher | Massachusetts Medical Society |
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| spelling | mit-1721.1/1249342022-09-29T09:00:05Z Sirtuins, Aging, and Medicine Guarente, Leonard Pershing Massachusetts Institute of Technology. Department of Biology Sirtuins were originally identified as antiaging proteins in model genetic organisms and have emerged as mediators of the beneficial effects of calorie restriction in mammals. The mammalian Sir2 orthologue, SIRT1, is an NAD-dependent deacetylase that is involved in many central pathways governing physiology and stress management. Genetic or pharmacologic activation of SIRT1 can benefit numerous diseases in murine models. Indeed, two different SIRT1-activating compounds are now in a diverse set of phase 1 or phase 2 human trials (ClinicalTrials.gov numbers, NCT00937326, NCT00964340, NCT01014117, NCT01018017, NCT01018628, NCT01262911, NCT01031108, and NCT01154101). Beyond SIRT1, there are six other mammalian sirtuins (SIRT2, 3, 4, 5, 6, and 7), and all may turn out to have therapeutic potential with the use of activators or inhibitors. Among these sirtuins, SIRT3 is extremely interesting, because it appears to suppress one of the contributing causes of aging itself, reactive oxygen species in mitochondria. Indeed, genetic polymorphisms in the SIRT3 promoter have been associated with extreme longevity in an Italian population,89,90 although these studies will have to be replicated in other groups. In conclusion, sirtuins are a unique class of proteins that link protein acetylation to metabolism and exert profound effects on mammalian physiology and diseases of aging. The development of drugs that target sirtuins to treat these diseases is ongoing. 2020-04-30T13:16:48Z 2020-04-30T13:16:48Z 2011-06 2019-12-05T15:54:43Z Article http://purl.org/eprint/type/JournalArticle 0028-4793 1533-4406 https://hdl.handle.net/1721.1/124934 Guarente, Leonard. "Sirtuins, Aging, and Medicine." New England Journal of Medicine 364, 23 (June 2011) : 2235-2244 © 2011 Massachusetts Medical Society. en http://dx.doi.org/10.1056/nejmra1100831 New England Journal of Medicine Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Massachusetts Medical Society New England Journal of Medicine |
| spellingShingle | Guarente, Leonard Pershing Sirtuins, Aging, and Medicine |
| title | Sirtuins, Aging, and Medicine |
| title_full | Sirtuins, Aging, and Medicine |
| title_fullStr | Sirtuins, Aging, and Medicine |
| title_full_unstemmed | Sirtuins, Aging, and Medicine |
| title_short | Sirtuins, Aging, and Medicine |
| title_sort | sirtuins aging and medicine |
| url | https://hdl.handle.net/1721.1/124934 |
| work_keys_str_mv | AT guarenteleonardpershing sirtuinsagingandmedicine |