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Potential role of sirtuins in livestock production

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Potential role of sirtuins in livestock production

Y. Ghinis-Hozumi1, A. Antaramian2, F. Villarroya3, E. Piña4 and O. Mora5-
1
Programa de Posgrado en Ciencias de la Producción y de la Salud Animal, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, México;
2
Instituto de Neurobiologı́a, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Querétaro, Qro. 76230, México; 3Departamento de Bioquı́mica y
Biologı́a Molecular e Instituto de Biomedicina (IBUB), Universitat de Barcelona y Centro de Investigación Biomédica en Red Fisiopatologı́a de la Obesidad y
Nutrición, Avenida Diagonal 645, Barcelona 08028, Spain; 4Departamento de Bioquı́mica, Facultad de Medicina, Universidad Nacional Autónoma de México,
Mexico City 04510, México; 5Laboratorio de Rumiologı́a y Metabolismo Nutricional (RuMeN), Secretarı́a de Posgrado, Facultad de Estudios Superiores-Cuautitlán,
Universidad Nacional Autónoma de México, Boulevard Bernardo Quintana 514-D, Colonia Arboledas, Querétaro, Qro. 76140, México

(Received 12 August 2011; Accepted 8 May 2012)

Sirtuins are NAD1-dependent histone and protein deacetylases, which have been studied during the last decade with a focus on
their role in lifespan extension and age-related diseases under normal and calorie-restricted or pathological conditions. However,
sirtuins also have the ability to regulate energy homeostasis as they can sense the metabolic state of the cell through the
NAD1/NADH ratio; hence, changes in the diet can modify the expression of these enzymes. Dietary manipulations are a common
practice currently being used in livestock production with favorable results, probably due in part to the enhanced activity of
sirtuins. Nevertheless, sirtuin expression in livestock species has not been a research target. For these reasons, the goal of this
review is to awaken interest in these enzymes for future detailed characterization in livestock species by presenting a general
introduction to what sirtuins are, how they work and what is known about their role in livestock.

Keywords: energy, livestock, metabolism, production, sirtuin

Implications
Sirtuin expression can be controlled by the diet, and genes
involved in glucose, lipid and amino acid metabolism can, in
turn, be regulated by sirtuins. Therefore, sirtuins represent a
potential target for dietary manipulations to improve live-
stock production. However, sirtuins are not yet being widely
studied in livestock species, opening a new field of research.
This review is intended to introduce sirtuins to animal
scientists interested in enhancing animal production to
achieve the food supply needed for the growing population.
Introduction
Livestock provide humans with numerous products and ser-
vices, of which food is the most important as a third of all
protein we consume derives from livestock. In addition,
there is a growing demand for food products of animal origin
in developing countries because of population and economic
growth (Food and Agriculture Organization of the United
Nations (FAO), 2009). Population growth is a problem
affecting food security. According to the United Nations’
2010 Revision of World Population Prospects, world population
-
E-mail: ofemora66@unam.mx or ofemora2001@yahoo.com.mx
will increase from 7 to 9.3 billion by the middle of the cen-
tury; in less than 40 years there will be 2.3 billion more
mouths to feed and this, together with increasing affluence,
means that food production will have to increase by 70%
(United Nations Organization Population Division, 2011). On
the basis of the magnitude of the challenge, technological
development is the best strategy to improve the efficiency in
animal productivity, quality of the derived products and
animal health. Some applications, such as those enhancing
reproduction (artificial insemination, embryo transfer and
embryo cryopreservation), have been in use for many dec-
ades (FAO, 1998). However, new DNA techniques, molecular
biology and technological reproductive applications are now
being tested (FAO, 2000). Among these new techniques,
dietary manipulation is becoming a common practice as it is
an easy way to enhance expression of specific genes
affecting metabolism and growth. Sirtuins represent a gene
family potentially controlled in this way.
Sirtuins (Sir two-like proteins) are mammalian homologs
of the silent information regulator 2 (Sir2) gene of Saccharomyces
cerevisiae, and they belong to the family of class III NAD1-
dependent histone deacetylases (HDAC III). In yeast, five sirtuins
have been identified (Sir2p and Hst1p to Hst4p), whereas in
humans and other mammals there are seven sirtuins (Sirt1 to
Sirt7; Frye, 2000; North and Verdin, 2004).

1
Ghinis-Hozumi, Antaramian, Villarroya, Piña and Mora
Research on Sir proteins initially focused on their gene-
silencing activity at the HM mating-type loci, telomeres and the
ribosomal DNA repeats (Smith et al., 1999; Cuperus et al.,
2000; Garcia and Pillus, 2002) as it was found that they dea-
cetylate nucleosomes to form heterochromatin (Braunstein
et al., 1993). However, it was later found that these enzymes
act as sensors of the cellular energy status, establishing a link
between gene silencing and metabolism in vivo (Denu, 2003).
Therefore, in the past decade, research was aimed at elucidat-
ing their structure (Sanders et al., 2010), enzymatic activity
(Taylor et al., 2008), biology and function in the cell (Shoba
et al., 2009), target proteins that include – besides histones –
transcription factors that regulate stress, metabolism and sur-
vival pathways (Shoba et al., 2009), as well as natural and
synthetic compounds that activate (Howitz et al., 2003; Camins
et al., 2010) and inhibit (Cen, 2010; Lawson et al., 2010) them.
Further general information on sirtuins is available in the
reviews by Dali-Youcef et al. (2007), Shoba et al. (2009), Imai
and Guarente (2010), Rajendran et al. (2011) and Cantó and
Auwerx (2012); information on the controversy arising about
the role of sirtuins in lifespan regulation can be found in the
work by Burnett et al. (2011); information on resveratrol, the
principal sirtuin activator being studied and its role in mam-
malian biology can be found in the review by Pervaiz (2003).
Enzymatic activity
Sirtuins possess a robust NAD1-dependent deacetylase
activity, which couples the cleavage of NAD1 to the deace-
tylation of a substrate. The reaction products are nicotina-
mide, a deacetylated product and the novel metabolite
o-acetyl-ADP-ribose (oAADPr), which is unique for this
reaction. The stoichiometric analysis of the reaction shows
a 1-to-1 conversion from NAD1/acetylated substrate to
nicotinamide/deacetylated product/oAADPr (Tanny and Moazed,
2001; Borra and Denu, 2006).
The enzyme first binds the acetylated substrate, followed
by NAD1, forming a ternary complex (Supplementary Figure
S1a). The nicotinamide-ribosyl bond is broken, and the acetyl
group of the substrate is transferred to the ADP-ribose moiety
of NAD1 (Supplementary Figure S1b). After this, nicotinamide is
released and an oxocarbenium ion-like intermediate is formed.
Next, the carbonyl oxygen of the acetyl-lysine performs a
nucleophilic attack on the nicotinamide ribose, forming an
iminium ion intermediate, which is then deprotonated, pro-
moting the formation of a cyclic intermediate. Finally, a
nucleophilic attack on this intermediate by a water molecule
liberates oAADPr and the deacetylated product (Supple-
mentary Figure S1c; Tanner et al., 2000; Tanny and Moazed,
2001; Marmorstein, 2004; Borra and Denu, 2006).
Biology
Sirtuins regulate mainly four biological processes: transcrip-
tion, cell cycle and apoptosis and energy homeostasis (Sauve
et al., 2006; Michan and Sinclair, 2007; Kong et al., 2009).
Transcription is generally negatively regulated by sirtuins
because of their deacetylation of histones; however, when
the sirtuin substrate is a transcription factor related to the
2
control of either growth, cell cycle or apoptosis, sirtuin regula-
tion may be positive and associated with extension of lifespan
(Sauve et al., 2006). The most recently discovered sirtuin sub-
strates comprise enzymes that regulate carbohydrate and lipid
metabolism, and in this particular case, regulation of the
enzymatic activity of the target protein can be either positive or
negative (Sauve et al., 2006; Michan and Sinclair, 2007). Sir-
tuins have been found in different subcellular locations, and
they modify diverse target substrates (Table 1). In addition,
each sirtuin has a specific physiological role within the different
tissues where they are expressed (Table 2).
Sirtuins in livestock
Sirtuins have been extensively studied in yeast, lower
organisms like fruit flies and worms, and mammals, mainly
rodents and humans, with special focus on their ability to
regulate lifespan and energy homeostasis; therefore, they
represent potential nutraceutical targets in metabolic syn-
drome and age-associated diseases like cancer and Alzhei-
mer’s disease. However, little benefit has been gained from
their ability to regulate glucose and lipid metabolism in
livestock production. When talking about livestock produc-
tion, it is understood that the main goal is to obtain more
animal (food) products in a more efficient way and in a
shorter period of time. Thus, sirtuins and the compounds that
regulate them should be studied, given their potential to
contribute to this objective.
Structure
Livestock species present all seven sirtuins (Supplementary
Figure S2) and, as all members of the Sir2 protein family, they
contain a core domain of around 260 amino acids, which is
highly conserved in prokaryotes and eukaryotes (Brachmann
et al., 1995). This core domain is formed by a Rossmann-fold
structure characteristic of NAD(P)1/NAD(P)H-binding pro-
teins (Finnin et al., 2001; Min et al., 2001), a zinc-binding
module containing a structural zinc atom coordinated by
four conserved cysteines and a flexible loop forming a
hydrophobic pocket, which may represent a class-specific
protein–protein interaction domain that gives a distinct
substrate specificity to each sirtuin (Finnin et al., 2001; Min
et al., 2001). In addition, differences at the N- and C-termini,
which can be identified from the Conserved Domain Data-
base (Marchler-Bauer et al., 2011), account for the variation
in binding partners and substrates, subcellular localization
and expression pattern, as well as different enzymatic
activities (Sherman et al., 1999; Borra et al., 2004; Haigis
and Sinclair, 2010).
Sirtuins and calorie restriction (CR)
Dietary manipulations, such as CR or intermittent fasting, are
known to affect gene expression in many tissues (Han and
Hickey, 2005). CR consists of a 20% to 50% reduction in energy
intake relative to ad libitum levels but without nutrient deficits
or malnutrition (Weindruch et al., 1986; Walford et al., 1987).
 Table 1 Cellular location and identified substrates for the seven mammalian sirtuins
Protein Cellular compartment Enzymatic activity Substrates References

Sirt1 Nucleus 2 cytoplasma Deacetylation Direct: Histones H3 and H4, FoxOs, Fulco et al. (2003), Brunet et al. (2004), Giannakou and Partridge (2004),
PPARs, PGC-1a, p53, AceCS1, GDH, Motta et al. (2004), Nemoto et al. (2004), Picard et al. (2004), Yeung et al.
ICDH, Tat, NF-kB, Ku70, MyoD (2004), Moynihan et al. (2005), Pagans et al. (2005), Rodgers et al. (2005),
Indirect: UCP2, UCP3, adiponectin Bordone et al. (2006), Hallows et al. (2006), Qiao and Shao (2006), Amat
et al. (2007), Gerhart-Hines et al. (2007), Kim et al. (2007), Michan and
Sinclair (2007), North and Sinclair (2007), Qiang et al. (2007), Saunders and
Verdin (2007), Nedachi et al. (2008), Schlicker et al. (2008), Shoba et al.
(2009), Wang and Tong (2009), Yu and Auwerx (2009), Sugden et al. (2010),
Planavila et al. (2011), Schug and Li (2011)
Sirt2 Cytoplasm Deacetylation Microtubules, a-tubulin, H4K16, Bae et al. (2004), Michan and Sinclair (2007), Saunders and Verdin (2007),
HoxA10, FoxO3a Wang et al. (2007)
Sirt3 Mitochondria (matrix) 2 nucleusa Deacetylation Direct: FoxO3a, AceCS2, LCAD, ICDH2, Shi et al. (2005), Hallows et al. (2006), North and Sinclair (2007), Saunders and
GDH, HMGS2, MnSOD, SOD2, OTC, Verdin (2007), Ahn et al. (2008), Jacobs et al. (2008), Schlicker et al. (2008),
NDUFA9, SDHA, MRPL10, Ku70, PPID Schwer and Verdin (2008), Sundaresan et al. (2008 and 2009), Palacios
Indirect: ETChain complexes I to IV, ATP et al. (2009), Shoba et al. (2009), Yu and Auwerx (2009), Cimen et al.
synthase, AMPK, UCP1 (2010), Hirschey et al. (2010), Huang et al. (2010), Kim et al. (2010), Kong
et al. (2010), Qiu et al. (2010), Shi et al. (2010), Shimazu et al. (2010), Shulga
et al. (2010), Tao et al. (2010), Yang et al. (2010), Giralt et al. (2011), Hallows
et al. (2011), Li and Kazgan (2011), Smith et al. (2011)
Sirt4 Mitochondria ADP-ribosylation Pancreatic GDH, IDE, ANT2, ANT3 Haigis et al. (2006), Ahuja et al. (2007), Nasrin et al. (2010)
Sirt5 Mitochondria (matrix, intermembrane) Deacetylation Histones, BSA, cytochrome c, CPS1 Schuetz et al. (2007), Schlicker et al. (2008), Nakagawa et al. (2009)
Sirt6 Nucleus Deacetylation ADP- Histone H3, DNA Pol b, BER enzymes, Liszt et al. (2005), Mostoslavsky et al. (2006), Rodgers and Puigserver (2006),
ribosylation p53, Hif1a Kanfi et al. (2008), Lombard et al. (2008), Shoba et al. (2009),
Yu and Auwerx (2009), Zhong et al. (2010), Li and Kazgan (2011)
Sirt7 Nucleolus Deacetylation RNA Pol I Ford et al. (2006), Saunders and Verdin (2007)
ETChain 5 electron transport chain; BER 5 base excision repair.
a
2 means translocation.

Sirtuins in livestock
3
Ghinis-Hozumi, Antaramian, Villarroya, Piña and Mora

Table 2 Physiological roles and tissues where sirtuins are present

Protein Physiological functions Tissues References

Sirt1 Cell proliferation, differentiation,
survival and apoptosis; stress
resistance; glucose and lipid
metabolism; gametogenesis,
embryogenesis and reproduction
Sirt2 Mitotic checkpoint; development;
antioxidant defense
Sirt3 Mitochondrial biogenesis and
respiration; antioxidant defense;
adaptive thermogenesis
Sirt4 Glucose and lipid metabolism
Sirt5 Link between energy metabolism and
aging; cellular stress response and
apoptosis
Sirt6 Genomic stability, aging, inflammation;
metabolism
Sirt7 Transcription of rDNA; growth
Liver, muscle, pancreas, brain, heart,
spinal cord, testis, ovaries, adipose
tissues
Adipose tissue (highest expression),
brain, heart, testis, skeletal muscle
Heart, brain, testis, liver, kidneys,
muscle, adipose tissues (mainly
brown)
Heart, brain, testis, kidneys, liver,
pancreas, skeletal muscle
Brain, testis, ovaries, skeletal muscle,
heart, kidneys, liver, lymphoblasts
Brain, spleen, liver, testis, ovaries,
skeletal muscle, heart, white
adipose tissue, kidneys
Liver, spleen, testis, thyroid gland
(high); heart, brain, muscle (low)
Mcburney et al. (2003), Sakamoto et al. (2004),
Michishita et al. (2005), Dali-Youcef et al.
(2007), Michan and Sinclair (2007), Shoba
et al. (2009)
Michishita et al. (2005), Dali-Youcef et al.
(2007), Jing et al. (2007), Shoba et al. (2009),
Kelly (2010)
Michishita et al. (2005), Ahn et al. (2008),
Shoba et al. (2009), Huang et al. (2010),
Kong et al. (2010)
Michishita et al. (2005), Shoba et al. (2009),
Huang et al. (2010), Nasrin et al. (2010)
Michishita et al. (2005), Mahlknecht et al.
(2006), Dali-Youcef et al. (2007), Schuetz
et al. (2007)
Liszt et al. (2005), Michishita et al. (2005),
Dali-Youcef et al. (2007), Kanfi et al. (2007),
Lombard et al. (2007), Li and Kazgan, (2011)
Ford et al. (2006), Shoba et al. (2009)

Table 3 Effects of calorie restriction on sirtuin expression in different tissues

Protein Upregulation Downregulation References

Sirt1 Brain, kidney, muscle, WAT, liver Liver Cohen et al. (2004), Wang et al. (2007), Chen et al. (2008)
Sirt2 WAT, kidney Wang et al. (2007)
Sirt3 WAT, BAT Shi et al. (2005)
Sirt4 Pancreas Haigis et al. (2006)
Sirt5 Liver Nakagawa et al. (2009)
Sirt6 Heart, brain, adipose tissues, liver, kidney Kanfi et al. (2008)
Sirt7 Not yet determined
WAT 5 white adipose tissue; BAT 5 brown adipose tissue.

Environmental and genetic signaling pathways can be turned
on by nutrient availability and utilization, thereby extending
lifespan and retarding age-related diseases in many organisms
ranging from yeast to mammals (Walford et al., 1987; Bordone
and Guarente, 2005).
Under normal metabolic conditions, glucose is metabolized
to pyruvate, stimulating either respiration or fermentation,
depending on the oxygen availability. When glucose is limited,
carbon skeletons are directed to the mitochondrial tricarboxylic
acid cycle, promoting the electron transport and respiration
processes (Lin et al., 2002). As a result, ATP is produced in
higher amounts, slowing down the rate of glycolysis, and NADH
is re-oxidized to NAD1, increasing the NAD1/NADH ratio in the
cell (Lin et al., 2002; Wolf, 2006).
Members of the sirtuin family establish a tight linkage
between nutritional status and longevity by regulating stress
management and energy homeostasis in response to the
cellular energy status, as measured by the NAD1/NADH ratio
(Lin et al., 2002; Schug and Li, 2011). Under CR conditions,
sirtuin activities overlap and combine to mediate metabo-
lism, cell growth, oxidative stress responses and apoptosis
(Shi et al., 2005). For a long time, Sirt1 was the only member
of this family implicated in the CR response; however,
expression and enzymatic activity of the seven mammalian
sirtuins are now known to be differently regulated by CR
(Table 3). Therefore, sirtuins emerge as crucial sensors of
changes in NAD1 concentrations as a result of fasting,
dietary restriction or oxidative stress (Rodgers and Puigser-
ver, 2007), regulating the cellular response to these stimuli.
Experiments measuring sirtuin expression after dietary
restriction in livestock have not yet been carried out. How-
ever, there are numerous reports dealing with the effects of
dietary restriction on production and reproduction in live-
stock. For instance, in 2010, Villeneuve et al. tested the
effects of dietary restriction on reproduction and lactation in
prepubertal ewe lambs and on growth performance of their
offspring over two breeding seasons. Three diets with a
concentrate-to-forage ratio of 93 : 7 (ad libitum), 69 : 31

4

(restricted) and 40 : 60 (high quality forage), respectively,
were offered randomly for 75 days. The results were that, at
the end of the experiments, ewes fed with the restricted diet
produced a higher volume of high quality milk, as measured
by the milk protein and milk fat yield, in addition to better
growth performance in their offspring. Therefore, we deduce
that the results obtained by these groups can be due, in part,
to the action of sirtuins, although they were not mentioned.
Potential role in livestock production
There are few studies making reference to sirtuins in live-
stock species. A summary of the information available in
poultry, swine and bovine is presented below.
In poultry, the first report about a chicken sirtuin was in 2003
by Senawong et al., who investigated the chicken ovalbumin
upstream promoter transcription factor (COUP-TF) interacting
proteins (CTIP) 1 and 2. These proteins have been related to
hematopoietic cell development and immune system malig-
nancies. Originally characterized as CTIPs, they are now known
to act as transcriptional repressors, but the mechanism by
which they do so is still not clear. The initial observation that
repression was not inhibited by trichostatin A, a known class I
and II HDAC inhibitor, raised the possibility of an interaction
with a class III HDAC. After co-transfection and chromatin
immunoprecipitation assays, the authors found that CTIP2
interacts physically with Sirt1, which enhances CTIP2-mediated
transcriptional repression. These results are relevant as previous
reports on the repressive activities of CTIPs show that pro-
liferative diseases in mammals are closely related to dysregu-
lated expression of CTIPs (Avram et al., 2002).
In bovines, the first work on sirtuins was reported by our
group (Ghinis-Hozumi et al., 2011). We used bovines as a
model of ruminant animals, and our interest in sirtuins is
because of their regulatory role in gluconeogenesis and lipid
metabolism. We obtained the Sir2 family hallmark sequence
motifs for Sirt1 to Sirt5 and the expression profiles for Sirt1
and Sirt3 in liver, muscle and subcutaneous adipose tissue of
bulls and 3-day-old calves. Under normal conditions, sirtuin
expression in bovines is similar to what has been reported
for other species when undergoing energy deprivation.
In swine, sirtuins have been more widely studied. For
instance, in 2008, Bai et al. analyzed the effects of resveratrol
and nicotinamide on Sirt1 regulation of preadipocyte differ-
entiation; they found that Sirt1 was actively expressed
throughout differentiation, and by adding resveratrol or nicoti-
namide, Sirt1 expression was regulated in a positive or negative
manner, respectively. Jin et al. (2009) fully characterized the
seven swine sirtuins, including their chromosomal mapping,
phylogenetic analysis, nucleotide and amino acid sequences
and tissue expression profiles, which showed that all sirtuins
were most highly expressed in brain and testis. Also in 2009,
Shan et al. characterized porcine Sirt1 by sequence and phylo-
genetical analysis and determined the expression profiles in
different adipose tissues of young and adult animals in order to
compare age-related differences as well as the effect of
resveratrol on Sirt1 expression. Later, Shan et al. (2010) mea-
sured the expression of Sirt1, together with two adipose lipases
Sirtuins in livestock
(adipose triglyceride lipase and hormone-sensitive lipase) in
two different pig breeds, a lean one and a fat one, and analyzed
the effect of insulin treatment on them. This group found that
Sirt1 expression is higher in lean animals, which is consistent
with reports on humans, and that insulin is a negative regulator
of the three enzymes examined. Finally, an applied study was
made available by Weber et al. (2010), who evaluated the
effect of a high fiber diet on the intestinal tract of growing,
female pigs and observed a decrease in liver mass and energy
stores and an increase in plasma triglycerides, in addition
to higher Sirt1, PGC-1a (peroxisome proliferator-activated
receptor-g coactivator) and CoxII (cyclooxygenase-II) expres-
sion, suggesting a more efficient energy utilization in this tissue.
In summary, Bai et al. (2008) and Jin et al. (2009) studied porcine
sirtuins, focusing on their role as models of human physiology for
the discovery of therapeutic treatments; Shan et al. (2009 and
2010) focused on the potential use of Sirt1 regulation to control
fat deposition in pigs, which is higher in adult pigs and lean
breeds, and Weber et al. (2010) performed the first application,
regulating sirtuin expression by dietary manipulations.
Conclusions and future perspectives
Sirtuins are, with no doubt, a family of proteins arising
interest in many research areas and, from the information
presented above, it is clear that they play an important role
in the regulation of energy homeostasis in livestock species,
as they do in rodents and humans. However, further research
on sirtuin expression and regulation in these species is
required to determine if and how they promote growth
performance and production. In this context, it is necessary
to establish the best method to improve these productive
parameters, taking advantage of the information about sir-
tuins available from other species and extrapolating it to
livestock species. We are confident that research in this field
will yield valuable information on sirtuin function as well as
on ways to improve production systems.
Acknowledgments
Yumi Ghinis-Hozumi thanks CONACYT for a scholarship at the
Facultad de Estudios Superiores-Cuautitlán, UNAM, and grant
55429 from SEP-CONACYT (SEP (Ministry of Public Education);
Consejo Nacional de Ciencia y Tecnologı́a, México City, México).
The authors also thank Dorothy Pless (INB (Neurobiology Insti-
tute)-UNAM, Querétaro, Qro., México) for revising the English
manuscript.
Supplementary materials
For supplementary material referred to in this article, please
visit http://dx.doi.org/doi:10.1017/S1751731112001115
References
Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX and Finkel T
2008. A role for the mitochondrial deacetylase Sirt3 in regulating energy
homeostasis. Proceedings of the National Academy of Sciences of the United
States of America 105, 14447–14452.
5
Ghinis-Hozumi, Antaramian, Villarroya, Piña and Mora
Ahuja N, Schwer B, Carobbio S, Waltregny D, North BJ, Castronovo V,
Maechler P and Verdin E 2007. Regulation of insulin secretion by SIRT4, a
mitochondrial ADP-ribosyltransferase. The Journal of Biological Chemistry 282,
33583–33592.
Amat R, Solanes G, Giralt M and Villarroya F 2007. SIRT1 is involved in
glucocorticoid-mediated control of uncoupling protein-3 gene transcription. The
Journal of Biological Chemistry 282, 34066–34076.
Avram D, Fields A, Senawong T, Topark-Ngarm A and Leid M 2002. COUP-TF
(chicken ovalbumin upstream promoter transcription factor)-interacting
protein 1 (CTIP1) is a sequence-specific DNA binding protein. The Biochemical
Journal 368, 555–563.
Bae NS, Swanson MJ, Vassilev A and Howard BH 2004. Human histone
deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10.
Journal of Biochemistry 135, 695–700.
Bai L, Pang WJ, Yang YJ and Yang GS 2008. Modulation of Sirt1 by resveratrol
and nicotinamide alters proliferation and differentiation of pig preadipocytes.
Molecular and Cellular Biochemistry 307, 129–140.
Bordone L and Guarente L 2005. Calorie restriction, Sirt1 and metabolism:
understanding longevity. Nature Reviews. Molecular Cell Biology 6, 298–305.
Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J, McDonagh T,
Lemieux M, McBurney M, Szilvasi A, Easlon EJ, Lin SJ and Guarente L 2006. Sirt1
regulates insulin secretion by repressing UCP2 in pancreatic beta cells. Public
Library of Science Biology 4, e31. Erratum in: Public Library of Science Biology
(2006) 4, e295.
Borra MT and Denu JM 2006. The enzymology of SIR2 proteins. In Histone
deacetylases: transcriptional regulation and other cellular functions (ed.
E Verdin), pp. 219–235. Humana Press Inc., New Jersey, USA.
Borra MT, Langer MR, Slama JT and Denu JM 2004. Substrate specificity and
kinetic mechanism of the Sir2 family of NAD1-dependent histone/protein
deacetylases. Biochemistry 43, 9877–9887.
Brachmann CB, Sherman JM, Devine SE, Cameron EE, Pillus L and Boeke JD
1995. The SIR2 gene family, conserved from bacteria to humans, functions in
silencing, cell cycle progression, and chromosome stability. Genes and
Development 9, 2888–2902.
Braunstein M, Rose AB, Holmes SG, Allis CD and Broach JR 1993. Transcriptional
silencing in yeast is associated with reduced nucleosome acetylation. Genes and
Development 7, 592–604.
Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE,
Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair
DA, Alt FW and Greenberg ME 2004. Stress-dependent regulation of FOXO
transcription factors by the SIRT1 deacetylase. Science 303, 2011–2015.
Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvári M, Piper MD, Hoddinott
M, Sutphin GL, Leko V, McElwee JJ, Vazquez-Manrique RP, Orfila AM, Ackerman
D, Au C, Vinti G, Riesen M, Howard K, Neri C, Bedalov A, Kaeberlein M, Soti C,
Partridge L and Gems D 2011. Absence of effects of Sir2 overexpression on
lifespan in C. elegans and drosophila. Nature 477, 482–485.
Camins A, Sureda FX, Junyent F, Verdaguer E, Folch J, Pelegri C, Vilaplana J,
Beas-Zarate C and Pallàs M 2010. Sirtuin activators: designing molecules to
extend life span. Biochimica et Biophysica Acta 1799, 740–749.
Cantó C and Auwerx J 2012. Targeting sirtuin 1 to improve metabolism: all you
need is NAD1? Pharmacological Reviews 64, 166–187.
Cen Y 2010. Sirtuins inhibitors: the approach to affinity and selectivity.
Biochimica et Biophysica Acta 1804, 1635–1644.
Chen D, Bruno J, Easlon E, Lin S-J, Cheng H-L, Alt FW and Guarente L 2008.
Tissue-specific regulation of SIRT1 by calorie restriction. Genes and Development
22, 1753–1757.
Cimen H, Han MJ, Yang Y, Tong Q, Koc H and Koc EC 2010. Regulation of
succinate dehydrogenase activity by SIRT3 in mammalian mitochondria.
Biochemistry 49, 304–311.
Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT,
Gorospe M, de Cabo R and Sinclair DA 2004. Calorie restriction promotes
mammalian cell survival by inducing the SIRT1 deacetylase. Science 305,
390–392.
Cuperus G, Shafaatian R and Shore D 2000. Locus specificity determinants in the
multifunctional yeast silencing protein Sir2. The European Molecular Biology
Organization Journal 19, 2641–2651.
Dali-Youcef N, Lagouge M, Froelich S, Koehl C, Schoonjans K and Auwerx J
2007. Sirtuins: the ‘magnificent seven’, function, metabolism and longevity.
Annals of Medicine 39, 335–345.
6
Denu JM 2003. Linking chromatin function with metabolic networks: Sir2
family of NAD(1)-dependent deacetylases. Trends in Biochemical Sciences 28,
41–48.
Drummond AJ, Ashton B, Buxton S, Cheung M, Cooper A, Duran C, Field M,
Heled J, Kearse M, Markowitz S, Moir R, Stones-Havas S, Sturrock S, Thierer T
and Wilson A 2011. Geneious v5.4. Retrieved January 17, 2012, from http://
www.geneious.com/ (downloaded version Geneious v5.5.6).
Finnin MS, Donigian JR and Pavletich NP 2001. Structure of the histone
deacetylase SIRT2. Nature Structural Biology 8, 621–625.
Food and Agriculture Organization of the United Nations (FAO) 1998.
Biotechnology developments and their potential impacts on the livestock and
meat sectors. Committee on Commodity Problems. Intergovernmental Group on
Meat, Cape Town, Republic of South Africa. Retrieved April 29, 2011, from
http://www.fao.org/docrep/meeting/W9681E.htm
FAO 2000. FAO statement on biotechnology. Biotechnology in Food and
Agriculture, Rome, Italy. Retrieved May 30, 2011, from http://www.fao.org/
biotech/fao-statement-on-biotechnology/en/
FAO 2009. The State of Food and Agriculture: Livestock in the Balance, Rome,
Italy. Retrieved April 29, 2011, from http://www.fao.org/docrep/012/i0680e/
i0680e00.htm
Ford E, Voit R, Liszt G, Magin C, Grummt I and Guarente L 2006. Mammalian
Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes and
Development 20, 1075–1080.
Frye RA 2000. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like
proteins. Biochemical and Biophysical Research Communications 273, 793–798.
Fulco M, Schiltz RL, Iezzi S, King MT, Zhao P, Kashiwaya Y, Hoffman E, Veech RL
and Sartorelli V 2003. Sir2 regulates skeletal muscle differentiation as a
potential sensor of the redox state. Molecular Cell 12, 51–62. Erratum in:
Molecular Cell (2005) 20, 491.
Garcia SN and Pillus L 2002. A unique class of conditional sir2 mutants displays
distinct silencing defects in Saccharomyces cerevisiae. Genetics 162, 721–736.
Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW,
Wu Z and Puigserver P 2007. Metabolic control of muscle mitochondrial
function and fatty acid oxidation through SIRT1/PGC-1alpha. The European
Molecular Biology Organization Journal 26, 1913–1923.
Ghinis-Hozumi Y, González-Gallardo A, González-Dávalos L, Antaramian A,
Villarroya F, Shimada A, Varela-Echavarrı́a A and Mora O 2011. Bovine sirtuins:
initial characterization and expression of Sirt1 and Sirt3 in liver, muscle, and
adipose tissue. Journal of Animal Science 89, 2529–2536.
Giannakou ME and Partridge L 2004. The interaction between FOXO and SIRT1:
tipping the balance towards survival. Trends in Cell Biology 14, 408–412.
Giralt A, Hondares E, Villena JA, Ribas F, Dı́az-Delfı́n J, Giralt M, Iglesias R and
Villarroya F 2011. Peroxisome proliferator-activated receptor-gamma coactiva-
tor-1alpha controls transcription of the Sirt3 gene, an essential component of
the thermogenic brown adipocyte phenotype. The Journal of Biological
Chemistry 286, 16958–16966.
Haigis MC and Sinclair DA 2010. Mammalian sirtuins: biological insights and
disease relevance. Annual Review of Pathology 5, 253–295.
Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ,
Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA,
Weindruch R, Alt FW and Guarente L 2006. SIRT4 inhibits glutamate
dehydrogenase and opposes the effects of calorie restriction in pancreatic beta
cells. Cell 126, 941–954.
Hallows WC, Lee S and Denu JM 2006. Sirtuins deacetylate and activate
mammalian acetyl-CoA synthetases. Proceedings of the National Academy of
Sciences of the United States of America 103, 10230–10235.
Hallows WC, Yu W, Smith BC, Devries MK, Ellinger JJ, Someya S, Shortreed MR,
Prolla T, Markley JL, Smith LM, Zhao S, Guan KL and Denu JM 2011. Sirt3
promotes the urea cycle and fatty acid oxidation during dietary restriction.
Molecular Cell 41, 139–149. Erratum in: Molecular Cell (2011) 41, 493.
Han E-S and Hickey M 2005. Microarray evaluation of dietary restriction. The
Journal of Nutrition 135, 1343–1346.
Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter
CA, Harris C, Biddinger S, Ilkayeva OR, Stevens RD, Li Y, Saha AK, Ruderman NB,
Bain JR, Newgard CB, Farese Jr. RV, Alt FW, Kahn CR and Verdin E 2010. SIRT3
regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation.
Nature 464, 121–125.
Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE,
Chung P, Kisielewski A, Zhang LL, Scherer B and Sinclair DA 2003. Small

molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.
Nature 425, 191–196.
Huang JY, Hirschey MD, Shimazu T, Ho L and Verdin E 2010. Mitochondrial
sirtuins. Biochimica et Biophysica Acta 1804, 1645–1651.
Imai S and Guarente L 2010. Ten years of NAD-dependent SIR2 family
deacetylases: implications for metabolic diseases. Trends in Pharmacological
Sciences 31, 212–220.
Jacobs KM, Pennington JD, Bisht KS, Aykin-Burns N, Kim HS, Mishra M, Sun L,
Nguyen P, Ahn BH, Leclerc J, Deng CX, Spitz DR and Gius D 2008. SIRT3 interacts
with the daf-16 homolog FOXO3a in the mitochondria, as well as increases
FOXO3a dependent gene expression. International Journal of Biological
Sciences 4, 291–299.
Jin D, Tan HJ, Lei T, Gan L, Chen XD, Long QQ, Feng B and Yang ZQ 2009. Molecular
cloning and characterization of porcine sirtuin genes. Comparative Biochemistry and
Physiology – Part B, Biochemistry and Molecular Biology 153, 348–358.
Jing E, Gesta S and Kahn CR 2007. SIRT2 regulates adipocyte differentiation
through FoxO1 acetylation/deacetylation. Cell Metabolism 6, 105–114.
Kanfi Y, Shalman R, Peshti V, Pilosof SN, Gozlan YM, Pearson KJ, Lerrer B,
Moazed D, Marine JC, de Cabo R and Cohen HY 2008. Regulation of SIRT6
protein levels by nutrient availability. Federation of European Biochemical
Societies Letters 582, 543–548.
Kelly G 2010. A review of the sirtuin system, its clinical implications, and the
potential role of dietary activators like resveratrol: part 1. Alternative Medicine
Review: A Journal of Clinical Therapeutic 15, 245–263.
Kim EJ, Kho JH, Kang MR and Um SJ 2007. Active regulator of SIRT1 cooperates
with SIRT1 and facilitates suppression of p53 activity. Molecular Cell 28, 277–290.
Kim HS, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD,
van der Meer R, Nguyen P, Savage J, Owens KM, Vassilopoulos A, Ozden O,
Park SH, Singh KK, Abdulkadir SA, Spitz DR, Deng CX and Gius D 2010. SIRT3 is
a mitochondria-localized tumor suppressor required for maintenance of
mitochondrial integrity and metabolism during stress. Cancer Cell 17, 41–52.
Kong XX, Wang R, Liu XJ, Zhu LL, Shao D, Chang YS and Fang FD 2009. Function
of SIRT1 in physiology. Biochemistry 74, 703–708.
Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y, Fang F and Chang Y 2010. Sirtuin 3,
a new target of PGC-1alpha, plays an important role in the suppression of ROS and
mitochondrial biogenesis. Public Library of Science One 5, e11707.
Larkin MA, Blackshields G, Brown NP, Chenna R, Mc-Gettigan PA, McWilliam H,
Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ and Higgins
DG 2007. Clustal W and Clustal X version 2.0. Bioinformatics 23, 2947–2948.
Lawson M, Uciechowska U, Schemies J, Rumpf T, Jung M and Sippl W 2010.
Inhibitors to understand molecular mechanisms of NAD(1)-dependent
deacetylases (sirtuins). Biochimica et Biophysica Acta 1799, 726–739.
Li X and Kazgan N 2011. Mammalian sirtuins and energy metabolism.
International Journal of Biological Sciences 7, 575–587.
Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, Culotta VC, Fink GR
and Guarente L 2002. Calorie restriction extends Saccharomyces cerevisiae
lifespan by increasing respiration. Nature 418, 344–348.
Liszt G, Ford E, Kurtev M and Guarente L 2005. Mouse Sir2 homolog SIRT6 is a
nuclear ADP-ribosyltransferase. The Journal of Biological Chemistry 280,
21313–21320.
Lombard DB, Schwer B, Alt FW and Mostoslavsky R 2008. SIRT6 in DNA repair,
metabolism and ageing. Journal of Internal Medicine 263, 128–141.
Mahlknecht U, Ho AD, Letzel S and Voelter-Mahlknecht S 2006. Assignment of
the NAD-dependent deacetylase sirtuin 5 gene (SIRT5) to human chromosome
band 6p23 by in situ hybridization. Cytogenetic and Genome Research 112,
208–212.
Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott
C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, Hurwitz DI, Jackson JD,
Ke Z, Lanczycki CJ, Lu F, Marchler GH, Mullokandov M, Omelchenko MV,
Robertson CL, Song JS, Thanki N, Yamashita RA, Zhang D, Zhang N, Zheng C and
Bryant SH 2011. CDD: a Conserved Domain Database for the functional
annotation of proteins. Nucleic Acids Research 39, D225–D229.
Marmorstein R 2004. Structure and chemistry of the Sir2 family of NAD1-
dependent histone/protein deacetylases. Biochemical Society Transactions 32,
904–909.
McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, Webb JR, Lansdorp
PM and Lemieux M 2003. The mammalian SIR2alpha protein has a role in
embryogenesis and gametogenesis. Molecular and Cellular Biology 23, 38–54.
Sirtuins in livestock
Michan S and Sinclair D 2007. Sirtuins in mammals: insights into their biological
function. The Biochemical Journal 404, 1–13.
Michishita E, Park JY, Burneskis JM, Barrett JC and Horikawa I 2005.
Evolutionarily conserved and nonconserved cellular localizations and functions
of human SIRT proteins. Molecular Biology of the Cell 16, 4623–4635.
Min J, Landry J, Sternglanz R and Xu RM 2001. Crystal structure of a SIR2
homolog-NAD complex. Cell 105, 269–279.
Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P,
Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford
E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W,
Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L,
Mulligan R, Demple B, Yancopoulos GD and Alt FW 2006. Genomic instability,
aging-like phenotype in the absence of mammalian SIRT6. Cell 124, 315–329.
Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y,
McBurney M and Guarente L 2004. Mammalian SIRT1 represses forkhead
transcription factors. Cell 116, 551–563.
Moynihan KA, Grimm AA, Plueger MM, Bernal-Mizrachi E, Ford E, Cras-Méneur
C, Permutt MA and Imai S 2005. Increased dosage of mammalian Sir2 in
pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell
Metabolism 2, 105–117.
Nakagawa T, Lomb DJ, Haigis MC and Guarente L 2009. Sirt5 deacetylates
carbamoyl phosphate synthetase 1, regulates the urea cycle. Cell 137, 560–570.
Nasrin N, Wu X, Fortier E, Feng Y, Bare OC, Chen S, Ren X, Wu Z, Streeper RS and
Bordone L 2010. SIRT4 regulates fatty acid oxidation and mitochondrial gene
expression in liver and muscle cells. The Journal of Biological Chemistry 285,
31995–32002.
Nedachi T, Kadotani A, Ariga M, Katagiri H and Kanzaki M 2008. Ambient
glucose levels qualify the potency of insulin myogenic actions by regulating
SIRT1 and FoxO3a in C2C12 myocytes. American Journal of Physiology.
Endocrinology and Metabolism 294, E668–E678.
Nemoto S, Fergusson MM and Finkel T 2004. Nutrient availability regulates
SIRT1 through a forkhead-dependent pathway. Science 306, 2105–2108.
North BJ and Verdin E 2004. Sirtuins: Sir2-related NAD-dependent protein
deacetylases. Genome Biology 5, 224.1–224.12.
North BJ and Sinclair DA 2007. Sirtuins: a conserved key unlocking AceCS
Activity. Trends in Biochemical Sciences 32, 1–4.
Pagans S, Pedal A, North BJ, Kaehlcke K, Marshall BL, Dorr A, Hetzer-Egger C,
Henklein P, Frye R, McBurney MW, Hruby H, Jung M, Verdin E and Ott M 2005.
SIRT1 regulates HIV transcription via Tat deacetylation. Public Library of Science
Biology 3, e41.
Palacios OM, Carmona JJ, Michan S, Chen KY, Manabe Y, Ward III JL, Goodyear
LJ and Tong Q 2009. Diet and exercise signals regulate SIRT3 and activate AMPK
and PGC-1alpha in skeletal muscle. Aging 1, 771–783.
Pervaiz S 2003. Resveratrol: from grapevines to mammalian biology. FASEB
Journal: Official Publication of the Federation of American Societies for
Experimental Biology 17, 1975–1985.
Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado de
Oliveira R, Leid M, McBurney MW and Guarente L 2004. Sirt1 promotes fat
mobilization in white adipocytes by repressing PPAR-gamma. Nature 429,
771–776. Erratum in: Nature (2004) 430, 921.
Planavila A, Iglesias R, Giralt M and Villarroya F 2011. Sirt1 acts in association
with PPARa to protect the heart from hypertrophy, metabolic dysregulation, and
inflammation. Cardiovascular Research 90, 276–284.
Qiang L, Wang H and Farmer SR 2007. Adiponectin secretion is regulated by
SIRT1 and the endoplasmic reticulum oxidoreductase Ero1-La. Molecular and
Cellular Biology 27, 4698–4707.
Qiao L and Shao J 2006. SIRT1 regulates adiponectin gene expression through
Foxo1-C/enhancer-binding protein alpha transcriptional complex. The Journal of
Biological Chemistry 281, 39915–39924.
Qiu X, Brown K, Hirschey MD, Verdin E and Chen D 2010. Calorie restriction
reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metabolism
12, 662–667.
Rajendran R, Garva R, Krstic-Demonacos M and Demonacos C 2011. Sirtuins:
molecular traffic lights in the crossroad of oxidative stress, chromatin
remodeling, and transcription. Journal of Biomedicine and Biotechnology,
vol. 2011, Article ID 368276, 17pp, 2011, doi:10.1155/2011/368276.
Rodgers JT and Puigserver P 2006. Certainly can’t live without this: Sirt6. Cell
Metabolism 3, 77–78.
7
Ghinis-Hozumi, Antaramian, Villarroya, Piña and Mora
Rodgers JT and Puigserver P 2007. Fasting-dependent glucose and lipid
metabolic response through hepatic sirtuin 1. Proceedings of the National
Academy of Sciences of the United States of America 104, 12861–12866.
Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM and Puigserver P 2005.
Nutrient control of glucose homeostasis through a complex of PGC-1alpha and
SIRT1. Nature 434, 113–118.
Sakamoto J, Miura T, Shimamoto K and Horio Y 2004. Predominant expression
of Sir2alpha, an NAD-dependent histone deacetylase, in the embryonic mouse
heart and brain. Federation of European Biochemical Societies Letters 556,
281–286.
Sanders BD, Jackson B and Marmorstein R 2010. Structural basis for sirtuin
function: what we know and what we don’t. Biochimica et Biophysica Acta
1804, 1604–1616.
Saunders LR and Verdin E 2007. Sirtuins: critical regulators at the crossroads
between cancer and aging. Oncogene 26, 5489–5504.
Sauve AA, Wolberger C, Schramm VL and Boeke JD 2006. The biochemistry of
sirtuins. Annual Review of Biochemistry 75, 435–465.
Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CFW and Steegborn
C 2008. Substrates and regulation mechanisms for the human mitochondrial
sirtuins Sirt3 and Sirt5. Journal of Molecular Biology 382, 790–801.
Schuetz A, Min J, Antoshenko T, Wang CL, Allali-Hassani A, Dong A, Loppnau P,
Vedadi M, Bochkarev A, Sternglanz R and Plotnikov AN 2007. Structural basis of
inhibition of the human NAD1-dependent deacetylase SIRT5 by suramin.
Structure 15, 377–389.
Schug TT and Li X 2011. Sirtuin 1 in lipid metabolism and obesity. Annals of
Medicine 43, 198–211.
Schwer B and Verdin E 2008. Conserved metabolic regulatory functions of
sirtuins. Cell Metabolism 7, 104–112.
Senawong T, Peterson VJ, Avram D, Shepherd DM, Frye RA, Minucci S and Leid
M 2003. Involvement of the histone deacetylase SIRT1 in chicken ovalbumin
upstream promoter transcription factor (COUP-TF)-interacting protein 2-
mediated transcriptional repression. The Journal of Biological Chemistry 278,
43041–43050.
Shan T, Wang Y, Wu T, Liu C, Guo J, Zhang Y, Liu J and Xu Z 2009. Porcine sirtuin
1 gene clone, expression pattern, and regulation by resveratrol. Journal of
Animal Science 87, 895–904.
Shan T, Ren Y, Liu Y, Zhu L and Wang Y 2010. Breed difference and
regulation of the porcine Sirtuin 1 by insulin. Journal of Animal Science 88,
3909–3917.
Sherman JM, Stone EM, Freeman-Cook LL, Brachmann CB, Boeke JD and Pillus L
1999. The conserved core of a human SIR2 homologue functions in yeast
silencing. Molecular Biology of the Cell 10, 3045–3059.
Shi T, Wang F, Stieren E and Tong Q 2005. SIRT3, a mitochondrial sirtuin
deacetylase, regulates mitochondrial function and thermogenesis in brown
adipocytes. The Journal of Biological Chemistry 280, 13560–13567.
Shi T, Fan GQ and Xiao SD 2010. SIRT3 reduces lipid accumulation via AMPK
activation in human hepatic cells. Journal of Digestive Diseases 11, 55–62.
Shimazu T, Hirschey MD, Hua L, Dittenhafer-Reed KE, Schwer B, Lombard DB, Li
Y, Bunkenborg J, Alt FW, Denu JM, Jacobson MP and Verdin E 2010. SIRT3
deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and
regulates ketone body production. Cell Metabolism 12, 654–661.
Shoba B, Lwin ZM, Ling LS, Bay BH, Yip GW and Kumar SD 2009. Function of
sirtuins in biological tissues. The Anatomical Record 292, 536–543.
Shulga N, Wilson-Smith R and Pastorino JG 2010. Sirtuin-3 deacetylation of
cyclophilin D induces dissociation of hexokinase II from the mitochondria.
Journal of Cell Science 123, 894–902.
Smith JS, Caputo E and Boeke JD 1999. A genetic screen for ribosomal DNA
silencing defects identifies multiple DNA replication and chromatin-modulating
factors. Molecular and Cellular Biology 19, 3184–3197.
Smith BC, Settles B, Hallows WC, Craven MW and Denu JM 2011. SIRT3
substrate specificity determined by peptide arrays and machine learning.
American Chemical Society Chemical Biology 6, 146–157.
View publication stats
Sugden MC, Caton PW and Holness MJ 2010. PPAR control: it’s SIRTainly as easy
as PGC. The Journal of Endocrinology 204, 93–104.
Sundaresan NR, Samant SA, Pillai VB, Rajamohan SB and Gupta MP 2008. SIRT3
is a stress-responsive deacetylase in cardiomyocytes that protects cells from
stress-mediated cell death by deacetylation of Ku70. Molecular and Cellular
Biology 28, 6384–6401.
Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A and Gupta MP 2009.
Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-
dependent antioxidant defense mechanisms in mice. The Journal of Clinical
Investigation 119, 2758–2771.
Tanner KG, Landry J, Sternglanz R and Denu JM 2000. Silent information
regulator 2 family of NAD-dependent histone/protein deacetylases generates a
unique product, 1-O-acetyl-ADP-ribose. Proceedings of the National Academy of
Sciences of the United States of America 97, 14178–14182.
Tanny JC and Moazed D 2001. Coupling of histone deacetylation to NAD
breakdown by the yeast silencing protein Sir2: evidence for acetyl transfer from
substrate to an NAD breakdown product. Proceedings of the National Academy
of Sciences of the United States of America 98, 415–420.
Tao R, Coleman MC, Pennington JD, Ozden O, Park SH, Jiang H, Kim HS, Flynn
CR, Hill S, Hayes McDonald W, Olivier AK, Spitz DR and Gius D 2010. Sirt3-
mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD
activity in response to stress. Molecular Cell 40, 893–904.
Taylor DM, Maxwell MM, Luthi-Carter R and Kazantsev AG 2008. Biological and
potential therapeutic roles of sirtuin deacetylases. Cellular and Molecular Life
Sciences 65, 4000–4018.
United Nations Organization Population Division 2011. World Population
Prospects: The 2010 Revision. Press Release, New York, USA. Retrieved
May 5, 2011, from http://esa.un.org/unpd/wpp/Other-Information/Press_Release_
WPP2010.pdf
Villeneuve L, Cinq-Mars D and Lacasse P 2010. Effects of restricted feeding of
prepubertal ewe lambs on reproduction and lactation performances over two
breeding seasons. Animal 4, 1997–2003.
Walford RL, Harris SB and Weindruch R 1987. Dietary restriction and aging:
historical phases, mechanisms and current directions. The Journal of Nutrition
117, 1650–1654.
Wang F and Tong Q 2009. SIRT2 suppresses adipocyte differentiation by
deacetylating FOXO1 and enhancing FOXO1’s repressive interaction with
PPARgamma. Molecular Biology of the Cell 20, 801–808.
Wang F, Nguyen M, Qin FX and Tong Q 2007. SIRT2 deacetylates FOXO3a in
response to oxidative stress and caloric restriction. Aging Cell 6, 505–514.
Weber TE, Trabue SL, Ziemer CJ and Kerr BJ 2010. Evaluation of elevated dietary
corn fiber from corn germ meal in growing female pigs. Journal of Animal
Science 88, 192–201.
Weindruch R, Walford RL, Fligiel S and Guthrie D 1986. The retardation of aging
in mice by dietary restriction: longevity, cancer, immunity and lifetime energy
intake. The Journal of Nutrition 116, 641–654.
Wolf G 2006. Calorie restriction increases life span: a molecular mechanism.
Nutrition Reviews 64, 89–92.
Yang Y, Cimen H, Han MJ, Shi T, Deng JH, Koc H, Palacios OM, Montier L, Bai Y,
Tong Q and Koc EC 2010. NAD1-dependent deacetylase SIRT3 regulates
mitochondrial protein synthesis by deacetylation of the ribosomal protein
MRPL10. The Journal of Biological Chemistry 285, 7417–7429.
Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA and Mayo MW
2004. Modulation of NF-kappaB-dependent transcription and cell survival by
the SIRT1 deacetylase. The European Molecular Biology Organization Journal
23, 2369–2380.
Yu J and Auwerx J 2009. The role of sirtuins in the control of metabolic
homeostasis. Annals of the New York Academy of Sciences 1173, E10–E19.
Zhong L, D’Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes
A, Marinelli B, Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O,
Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM and
Mostoslavsky R 2010. The histone deacetylase Sirt6 regulates glucose
homeostasis via Hif1alpha. Cell 140, 280–293.