Open AccessYeast sirtuins and the regulation of aging
Author(s) -
Wierman Margaret B.,
Smith Jeffrey S.
Publication year - 2014
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1111/1567-1364.12115
Subject(s) - sirtuin , nad+ kinase , biology , saccharomyces cerevisiae , histone , sirt6 , sirt3 , longevity , genetics , gene silencing , microbiology and biotechnology , sirt2 , biochemistry , yeast , gene , enzyme
Abstract The sirtuins are a phylogenetically conserved family of NAD + ‐dependent protein deacetylases that consume one molecule of NAD + for every deacetylated lysine side chain. Their requirement for NAD + potentially makes them prone to regulation by fluctuations in NAD + or biosynthesis intermediates, thus linking them to cellular metabolism. The S ir2 protein from S accharomyces cerevisiae is the founding sirtuin family member and has been well characterized as a histone deacetylase that functions in transcriptional silencing of heterochromatin domains and as a pro‐longevity factor for replicative life span ( RLS ), defined as the number of times a mother cell divides (buds) before senescing. Deleting SIR2 shortens RLS , while increased gene dosage causes extension. Furthermore, S ir2 has been implicated in mediating the beneficial effects of caloric restriction ( CR ) on life span, not only in yeast, but also in higher eukaryotes. While this paradigm has had its share of disagreements and debate, it has also helped rapidly drive the aging research field forward. S . cerevisiae has four additional sirtuins, H st1, H st2, H st3, and H st4. This review discusses the function of S ir2 and the H st homologs in replicative aging and chronological aging, and also addresses how the sirtuins are regulated in response to environmental stresses such as CR .