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Recent studies show that levels of repressor element 1-silencing transcription factor (REST) increase with normal aging in mice and humans, and reduce neuronal excitation. In\n                    <jats:italic toggle=\"yes\">C. elegans,<\/jats:italic>\n                    increased expression of\n                    <jats:italic toggle=\"yes\">spr-4<\/jats:italic>\n                    , a functional REST homologue, increased the worm life span and is required for classical life span increase mediated by reduced DAF-2\/insulin-IGF-1 and increased DAF-16. Preliminary evidence shows that REST and FOXO1, a DAF-16, homologue increase during mammalian aging, and that REST activity is needed for the age-related FOXO1 increase. On the contrary, REST is activated in epilepsy and plays a role in the pathogenesis of Huntington's disease. A simple unifying hypothesis suggests that REST is a \u201cgoldilocks-effect factor\u201d: too little REST promotes excitotoxic activity, which in turn leads to neurodegenerative diseases such as Alzheimer's. Appropriate increased levels of REST maintain the excitation\/inhibition (E-I) balance by reducing potential excitotoxic activity. Increased levels of REST beyond this are toxic as neurons become dysfunctional due to loss of a neuronal phenotype.\n                  <\/jats:p>","DOI":"10.1089\/rej.2019.2287","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T02:51:32Z","timestamp":1574650292000},"page":"529-532","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased REST to Optimize Life Span?"],"prefix":"10.1177","volume":"22","author":[{"given":"James W.","family":"Larrick","sequence":"first","affiliation":[{"name":"Panorama Research Institute, Sunnyvale, California."},{"name":"Regenerative Sciences Institute, Sunnyvale, California."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R.","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"Panorama Research Institute, Sunnyvale, California."},{"name":"Regenerative Sciences Institute, Sunnyvale, California."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,12,13]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","unstructured":"Lu T Pan Y Kao S-Y et al. 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