Open Longevity Science, 2009, 3, 17-21 17
1876-326X/09 2009 Bentham Open
Calorie Restriction Mimetics: Examples and Mode of Action
British Longevity Society, UK
Abstract: The search for Calorie Restriction Mimetics (CRM) - compounds that mimic the genetic, biochemical and
physical actions of calorie restriction - is not a search for a ‘lazy dieters pill’. It is a quest aiming to clarify the basic
mechanisms of calorie restriction and develop strategies in order to prevent, treat or alleviate age-related conditions. The
development of CRM will add new and important assets in our armamentarium of anti-ageing therapies, with the ultimate
result of increasing healthy human lifespan. This Special Supplement on CRM is an attempt to discuss some agents which
may be used instead of calorie restriction itself. Agents such as resveratrol, metformin, carnosine and Rimonabant are
mainstream oral therapies already used by millions of people for other clinical indications. New CRM such as NADH,
gugulipids and certain drugs that interfere with glucose metabolism can be also used as oral therapy. Less easily available
CRM such as oxaloacetic acid, naloxone, leptin, adiponectin, rapamycin and sirtuins are further examples of promising
agents. In order for the therapy to be effective, a combination of these must be used. This paper summarises the actions of
calorie restriction and then suggests several examples of possible CRM. Some of these examples can be used in everyday
Keywords: Calorie restriction, calorie restriction mimetics, health-span, hormesis.
Calorie restriction (CR) is discussed elsewhere in this
Supplement. Its practical aim is not only to increase average
and maximum lifespan in humans, but also to prolong the
'health-span' which is the number of years an organism can
live without any major chronic diseases . It may be
somewhat simplistic but practically useful to divide the ef-
fects of CR into three general categories: genetic, biochemi-
cal and physical. The following list is by no means exhaus-
tive but highlights some examples.
A. Genetic. These are effects at specific gene level which
can modulate transcription of enzymes or other fac-
tors. Perhaps the most promising CRM are those
which work on this level.
• Decreases the activity of p53 , and therefore modu-
lates apoptosis .
• Regulates Sir-2  and activates Sirt1 . Sirt1 is
activated to promote transcription of genes that deal
with the stress response and adaptation.
• Regulates Daf-16. AMPK (AMP Protein Activated
Kinase) is activated in the presence of Daf-16 .
B. Biochemical effects are those that directly influence
macromolecules, without an identifiable genetic ori-
• Reduces lipid peroxidation and generation of super-
• Reduces iNOS expression and COX2 expression ,
and increases NADH concentration within the mito-
*Address correspondence to this author at the British Longevity Society,
UK; E-mail: email@example.com
• Maintains DHEA levels .
• Modulates PPAR . Suppresses PGE-2, TNF-alpha
and CRP (thus reduces the inflammation response)
• Stimulates Brain-Derived Neurotropic Factor (BDNF)
C. Physical changes include clinically relevant and
measurable parameters, at the organismic level.:
• Reduces body weight and body temperature .
• Improves diastolic function. Lowers cholesterol,
blood pressure and pulse rate, and reduces blood glu-
cose levels .
• Increases muscle mass and reduces fat mass (includ-
ing intra-abdominal fat) .
• Improves memory and cognition [17, 18].
Calorie restriction mimetics (CRM) are drugs or chemi-
cal compounds which mimic the actions of CR. It is not suf-
ficient for a compound that mimics just one effect of CR to
be classified as a CRM. As an arbitrary guide, I propose that,
in order for a compound to be classified as a CRM, it has to
mimic at least two biochemical plus one genetic, or five bio-
chemical/physical effects of CR. This is a general attempt at
defining a CRM and further discussion is needed, although
initial attempts along these lines have already been made
, and in particular with regards to defining biomarkers in
calorie restriction has already taken place . Examples of
CRM that are already available and currently used for other
18 Open Longevity Science, 2009, Volume 3 Marios Kyriazis
Metformin is a receptor sensitizer, because it enhances
the sensitivity of insulin receptors on the surface of muscle
and fat cells . It can activate genes which reduce hepatic
production of glucose, thus reducing the risk of glycation
and other age-related damage. In addition, metformin re-
duces gene expression of enzymes which increase oxidation
of fatty acids. Further research is needed to clarify the ap-
proximate dose of metformin for CRM effects. Healthy peo-
ple who take metformin for its general anti-ageing benefits
use 500 mg twice a day. Side effects may include gastroin-
testinal problems and allergic reactions.
This is a polyphenol with proven beneficial cardiovascu-
lar effects and a potent CRM . In yeast, it stimulates Sir2
(silent information regulator), increasing DNA stability and
extending life-span by 70%. Resveratrol activates the human
homologue SIRT1 which results in reduced apoptosis in the
liver, blood and skin, and reduced risk of age-related chronic
disease. The dose of resveratrol is normally between 5 mg
and 15 mg daily, however the dose necessary to achieve
CRM effects has not yet been calculated. Long term adverse
effects are unknown, but no significant short term side ef-
fects have been reported.
Endocannabinoids are cannabis-like chemicals which
stimulate appetite and regulate energy balance. Overstimula-
tion of endocannabinoid receptor in the hypothalamus pro-
motes appetite and stimulates lipogenesis . It also blocks
adiponectin. Rimonabant (an anti-obesity drug) is an endo-
cannabinoid-1 receptor blocker, which reduces appetite, bal-
ances energy production and increases adiponectin which, in
turn, reduces intra-abdominal fat . Rimonabant improves
lipid profile, glucose tolerance, and waist measurement.
Therefore, it has effects similar to those of CR. It is taken 20
mg once daily, preferably with a mild calorie restricted diet.
The efficacy and long term adverse effects of rimonabant
have recently been questioned and further research is needed
to clarify these.
Agents which reduce abnormal protein accumulation
(aminoguanidine and carnosine) can also be CRM. These
prevent glycation and therefore reduce AGEs (Advance Gly-
cation End-products) formation . AGEs contribute to
extensive age-related damage such as accumulation of amy-
loid-beta implicated in Alzheimer's disease. CR reduces the
concentration of AGEs. The same mechanism is shared by
aminoguanidine and carnosine which prevent and eliminate
AGEs, therefore contributing towards the prevention of
chronic degenerative disease. No significant side effects
have been reported, and mild gastrointestinal problems usu-
ally improve after reducing the dose.
The agent exendin (exanatide, exanadin) reduces plasma
glucose, suppresses food intake and regulates glucose me-
tabolism . It is a GLP (Glucagon-Like Peptide) modula-
tor, able to increase brain function and protect the brain
against toxicity. Exanatide (Byetta®) was approved by the
Food and Drug Administration for treatment of Type 2 Dia-
betes in patients who are already on an oral diabetes medica-
tion. The product comes in pre-filled syringes and is injected
subcutaneously twice daily.
This agent inhibits the release of fatty acids from adipose
tissue and reduces blood concentration of very low density
lipoproteins and low density lipoproteins with a subsequent
reduction in triglyceride and cholesterol levels . It im-
proves growth hormone secretion and reduces lipid peroxi-
dation. Olbetam is indicated as adjunctive therapy to diet and
weight loss in the treatment of several lipid disorders. The
dosage is between 500-750 mg/day.
PPAR Gamma Modulators
Peroxisome proliferator-activated receptors (PPARs) are
members of the nuclear hormone receptor superfamily of
transcription factors that are related to retinoid, steroid and
thyroid hormone receptors. PPARs play an important role in
many cellular functions including lipid metabolism, cell pro-
liferation, differentiation, adipogenesis and inflammatory
signaling. Modulation of PPAR gamma generally reduces
inflammation, improves immunity and reduces blood glu-
cose. Two examples of PPAR modulators are:
a) Rosiglitazone (Avantia), an insulin-sensitizing drug
that is a ligand for PPAR-gamma . The dose is 4
mg once or twice a day.
b) Gugulipids, from the plant Commiphora mukul,
which block the PPAR-mediated differentiation of
preadipocytes into mature adipocytes .
Two very promising CRM (NADH/oxaloacetic acid and
Naloxone) are discussed elsewhere in this Supplement. Other
candidate CRM which are not readily available are listed
below. The list is merely an example of possible CRM and it
is by no means exhaustive. Further research regarding the
CRM effects of each compound may help in establishing
their mode of action. Furthermore, the clinical adverse ef-
fects of these agents have not been clarified and are best used
under expert specialist supervision.
This is a molecule, produced by adipocytes, that stimu-
lates fat metabolism and reduces body weight. A reduction
of dietary intake causes leptin levels to fall and this interferes
with the secretion of testosterone, progesterone, growth
hormone and thyroid hormones as a response for adaptation
. Therefore, leptin mediates the clinical effects of CR. As
a result, agents which affect leptin production must also be
classified as CRM. Together with insulin and ghrelin (a
growth hormone stimulator) leptin balances the ratio of ap-
petite promoters vs. appetite blockers in the hypothalamus in
the brain and so regulates homeostasis and food intake.
Leptin is stimulated by PPAR modulators such as rosiglita-
zone. Human recombinant leptin costs approximately $140
for 0.5 mg, but nicotinic acid can help increase its concentra-
tion. However, leptin mediates the effects of diabetic car-
diomyopathy  and its long term effects are not clear.
Calorie Restriction Mimetics Open Longevity Science, 2009, Volume 3 19
The first CRM described, inhibits glycolysis and mimics
some of the effects of CR, particularly increased insulin sen-
sitivity, reduced glucose levels and other biochemical
changes . Research is still under way to identify more
about its possible benefits on humans. What is known about
deoxyglucose is that it can be toxic in high dosages.
Modulators of Sirtuins
Sirtuins are histone deacetylases that catalyze deacetyla-
tion reaction in an NAD(+)-dependent manner . Activa-
tion of sirtuins improves longevity and health span in many
species. This can be achieved by STAC –sirtuin activating
compounds. Examples of STAC are chalchone , sirtinol,
which among other actions, reduces pro-inflammation me-
diators  and fisetin (a flavonoid, antioxidant compound).
Fisetin is a potent suppressor of some inflammatory cytoki-
nes/chemokines and an angiogenic factor .
Increases median and maximum lifespan in flies. In addi-
tion, it increases histone deacetylation .
An active ingredient extracted from the Garcinia cambo-
gia, reduces caloric intake and cholesterol  and it is cur-
rently used in weight control .
Isolated from the leaves of Gymnema sylvestre ,
gymnemoside modulates glucose metabolism.
Together with leptin, it takes part in fat metabolism. It is
activated by PPAR modulators such as rosiglitazone . It
enhances phosphorylation of AMPK , although it can
increase total and cardiovascular mortality . Human re-
combinant adiponectin is available for sale costing approx
$350 per 50 mcg.
An alkylating agent, it protects against toxic metabolites
of glucose. Iodoacetate prevents formation of disulfide
bonds, is a glycolysis-inhibitor and an anti-cancer agent .
Diapeptidyl peptidase-4 (DPP-4) is an enzyme that
modulates Glucagon-Like Peptide, allowing glucagon to
increase glucose concentration . DPP-4 inhibitors have
the opposite effect, reducing glucose plasma levels, and are
This protein fragment is released from the bowel follow-
ing a meal. It then inhibits food intake by acting on the hun-
ger centre in the hypothalamus . By reducing appetite
and glucose metabolism (actions similar to those seen in
CR), it can meet some of the criteria for consideration as a
Modulators of NPY
The neuropeptide Y (NPY) is a small protein fragment
which increases appetite, induces obesity and reduces the
metabolic rate. CR modulates the production of NPY by se-
lectively blocking receptors in the hippocampal region of the
brain and by stimulating others in the hypothalamus. Any
modulation of NPY release would result in exactly the same
clinical effects as those seen in CR .
It is known that CR downregulates TOR (target of ra-
pamycin) . Many longevity genes encode components of
TOR pathway, so rapamycin which is a TOR inhibitor, can
be classified as a CRM.
These block galanin (which increases appetite and re-
duces insulin) [49,50]. An example is the antagonist M35.
is a hormetic metabolic poison  that causes mild mi-
tochondrial uncoupling, interfering with energy production.
However, overdose is lethal. Nevertheless, metabolic poi-
sons with hormetic effects (such as oligomycin, carbonyl-
cyanide, rotenone, antimycin, and malonate) are being inves-
tigated as having not only CRM actions but also other health
Clearly, a CRM cannot mimic all of the actions of CR, so
it must be combined with other CRM which complement
each other, in order to cover as many actions of CR as possi-
For example, Acomplia, metformin and resveratrol can
be combined for maximum effect. It is worth noting that
Intermittent Fasting (IF) is an intervention that may mimic
the effects of CR itself. However, IF increases lifespan even
when the overall calories are not reduced. It appears that it is
the stress of fasting rather than the reduced calories that
cause the benefit. This supports the view that the stress of
fasting is a hormetic challenge which helps activate the pro-
tection pathways that are also active in CR . A search for
CRM can be extended to find IF mimetics such as RHEB, a
GTPase, which is a mediator through Daf16 and TOR .
The increased amount of research into CR has given us
promising directions into identifying effective agents which
reproduce the exact benefits of CR, without the need to fol-
low long calorie-restricted diets. The most promising and
clinically relevant CRM are those that reproduce at least one
genetic and two biochemical, or at least five biochemi-
cal/clinical benefits of CR. While research is continuing,
many physicians who already recommend these compounds
to their patients for other indications, have now started real-
ising that their treatment has an added possible health-
 Barzilai N, Bartke A. Biological approaches to mechanistically
understand the healthy life span extension achieved by calorie re-
striction and modulation of hormones. J Gerontol A Biol Sci Med
Sci 2009; 64(2): 187-91.
20 Open Longevity Science, 2009, Volume 3 Marios Kyriazis
 Bauer JH, Poon PC, Glatt-Deeley H, Abrams JM, Helfand SL.
Neuronal expression of p53 dominant-negative proteins in adult
Drosophila melanogaster extends life span. Curr Biol 2005; 15(22):
 Marzetti E, Lawler JM, Hiona A, Manini T, Seo AY, Leeuwen-
burgh C. Modulation of age-induced apoptotic signaling and cellu-
lar remodeling by exercise and calorie restriction in skeletal mus-
cle. Free Radic Biol Med 2008; 44(2): 160-8.
 Allard JS, Perez E, Zou S, de Cabo R. Dietary activators of Sirt1.
Mol Cell Endocrinol 2009; 299(1): 58-63.
 Jiang WJ. Sirtuins: novel targets for metabolic disease in drug
development. Biochem Biophys Res Commun 2008; 373(3): 341-4.
 Greer EL, Dowlatshahi D, Banko MR, et al. An AMPK-FOXO
pathway mediates longevity induced by a novel method of dietary
restriction in C. elegans. Curr Biol 2007; 17: 1646-56.
 Hyun DH, Emerson SS, Jo DG, Mattson MP, de Cabo R. Calorie
restriction up-regulates the plasma membrane redox system in brain
cells and suppresses oxidative stress during aging. Proc Natl Acad
Sci USA 2006; 103(52): 19908-12.
 Kim YJ, Kim HJ, No JK, Chung HY, Fernandes G. Anti-
inflammatory action of dietary fish oil and calorie restriction. Life
Sci 2006; 78(21): 2523-32.
 Yang H, Yang T, Baur JA, et al. Nutrient-sensitive mitochondrial
NAD+ levels dictate cell survi. J Clin Endocrinol Metab 1997;
 Lane MA, Ingram DK, Ball SS, Roth GS. Dehydroepiandrosterone
sulfate: a biomarker of primate aging slowed by calorie restriction.
J Clin Endocrinol Metab 1997; 82(7): 2093-6.
 Mulligan JD, Stewart AM, Saupe KW. Downregulation of plasma
insulin levels and hepatic PPARgamma expression during the first
week of caloric restriction in mice. Exp Gerontol 2008; 43(3): 146-
 Bosutti A, Malaponte G, Zanetti M, et al. Calorie restriction modu-
lates inactivity-induced changes in the inflammatory markers C-
reactive protein and pentraxin-3. Clin Endocrinol Metab 2008;
 Araya AV, Orellana X, Espinoza J. Evaluation of the effect of
caloric restriction on serum BDNF in overweight and obese sub-
jects: preliminary evidences. Endocrine 2008; 33(3): 300-4.
 Heilbronn LK, de Jonge L, Frisard MI, et al. Pennington CALERIE
Team. Effect of 6-month calorie restriction on biomarkers of lon-
gevity, metabolic adaptation, and oxidative stress in overweight in-
dividuals: a randomized controlled trial. JAMA 2006; 295(13):
 Redman LM, Ravussin E. Endocrine alterations in response to
calorie restriction in humans. Mol Cell Endocrinol 2009; 299(1);
 Weiss EP, Holloszy JO. Improvements in body composition, glu-
cose tolerance, and insulin action induced by increasing energy ex-
penditure or decreasing energy intake. J Nutr 2007; 137(4): 1087-
 Geng YQ, Guan JT, Xu MY, Xu XH, Fu YC. Behavioral study of
calorie-restricted rats from early old age. Conf Proc IEEE Eng Med
Biol Soc 2007; 2007: 2393-5.
 Witte AVM, Fobker R, Gellner S, Flöel KA. Caloric restriction
improves memory in elderly humans. Proc Natl Acad Sci USA
2009 [Epub ahead of print].
 Karasik D, Demissie S, Cupples LA, Kiel DP. Disentangling the
genetic determinants of human aging: biological age as an alterna-
tive to the use of survival measures. J Gerontol A Biol Sci Med Sci
2005; 60(5): 574-87.
 Ingram DK, Nakamura E, Smucny D, Roth GS, Lane MA. Strategy
for identifying biomarkers of aging in long-lived species. Exp
Gerontol 2001; 36(7): 1025-34.
 Anisimov VN, Berstein LM, Egormin PA, et al. Metformin slows
down aging and extends life span of female SHR mice. Cell Cycle
2008; 7(17): 2769-73.
 Wood JG, Rogina B, Lavu S, et al. Sirtuin activators mimic caloric
restriction and delay ageing in metazoans. Nature 2004; 430(7000):
 Zyromski NJ, Mathur A, Pitt HA, et al. Cannabinoid receptor-1
blockade attenuates acute pancreatitis in obesity by an adiponectin
mediated mechanism. J Gastrointest Surg 2009; 13(5): 831-8.
 Loh KY, Kew ST. Endocannabinoid system and cardio-metabolic
risk. Med J Malaysia 2008; 63(4): 348-50.
 Sourris KC, Forbes JM, Cooper ME. Therapeutic interruption of
advanced glycation in diabetic nephropathy: do all roads lead to
Rome? Ann N Y Acad Sci 2008; 1126: 101-6.
 Tews D, Lehr S, Hartwig S, Osmers A, Paßlack W, Eckel J. Anti-
apoptotic action of exendin-4 in INS-1 beta cells: comparative pro-
tein pattern analysis of isolated mitochondria. Horm Metab Res
2009; 41(4): 294-301.
 Salgin B, Marcovecchio ML, Humphreys SM, et al. Effects of
prolonged fasting and sustained lipolysis on insulin secretion and
insulin sensitivity in normal subjects. Am J Physiol Endocrinol Me-
tab 2009; 296(3): E454-61.
 Holguin F, Rojas M, Hart CM. The peroxisome proliferator acti-
vated receptor gamma (PPARgamma) ligand rosiglitazone modu-
lates bronchoalveolar lavage levels of leptin, adiponectin, and in-
flammatory cytokines in lean and obese mice. Lung 2007; 185(6):
 Nohr LA, Rasmussen LB, Straand J. Resin from the mukul myrrh
tree, guggul, can it be used for treating hypercholesterolemia? A
randomized, controlled study. Complement Ther Med 2009; 17(1):
 Sirotkin AV, Chrenková M, Nitrayová S, et al. Effects of chronic
food restriction and treatments with leptin or ghrelin on different
reproductive parameters of male rats. Peptides 2008; 29(8): 1362-8.
 Majumdar P, Chen S, George B, Sen S, Karmazyn M, Chakrabarti
S. Leptin and endothelin-1 mediated increased extracellular matrix
protein production and cardiomyocyte hypertrophy in diabetic heart
disease. Diabetes Metab Res Rev 2009 [Epub ahead of print].
 Ingram DK, Zhu M, Mamczarz J, et al. Calorie restriction mimet-
ics: an emerging research field. Aging Cell 2006; 5(2): 97-108.
 Gan L. Therapeutic potential of sirtuin-activating compounds in
Alzheimer's disease. Drug News Perspect 2007; 20(4): 233-9.
 Kahyo T, Ichikawa S, Hatanaka T, Yamada MK, Setou M. A novel
chalcone polyphenol inhibits the deacetylase activity of SIRT1 and
cell growth in HEK293T cells. J Pharmacol Sci 2008; 108(3): 364-
 Liu FC, Day YJ, Liou JT, Lau YT, Yu HP. Sirtinol attenuates he-
patic injury and pro-inflammatory cytokine production following
trauma-hemorrhage in male Sprague-Dawley rats. Acta Anaesthe-
siol Scand 2008; 52(5): 635-40.
 Lee JD, Huh JE, Jeon G, et al. Flavonol-rich RVHxR from Rhus
verniciflua Stokes and its major compound fisetin inhibits inflam-
mation-related cytokines and angiogenic factor in rheumatoid ar-
thritic fibroblast-like synovial cells and in vivo models. Int
Immunopharmacol 2009; 9(3): 268-76.
 Kang HL, Benzer S, Min KT. Life extension in Drosophila by
feeding a drug. Proc Natl Acad Sci USA 2002; 99(2): 838-43.
 Vasques CA, Rossetto S, Halmenschlager G, et al. Evaluation of
the pharmacotherapeutic efficacy of Garcinia cambogia plus Amor-
phophallus konjac for the treatment of obesity. Phytother Res 2008;
 Hayamizu K, Tomi H, Kaneko I, Shen M, Soni MG, Yoshino G.
Effects of Garcinia cambogia extract on serum sex hormones in
overweight subjects. Fitoterapia 2008; 79(4): 255-61.
 Zhu XM, Xie P, Di YT, Peng SL, Ding LS, Wang MK. Two new
triterpenoid saponins from Gymnema sylvestre. J Integr Plant Biol
2008; 50(5): 589-92.
 Kanaya AM, Harris T, Goodpaster BH, Tylavsky F, Cummings SR.
Adipocytokines attenuate the association between visceral adipos-
ity and diabetes in older adults; Health, Aging, and Body Composi-
tion (ABC) Study. Diabetes Care 2004; 27(6): 1375-80.
 Kondo M, Shibata R, Miura R, et al. Caloric restriction stimulates
revascularization in response to ischemia via adiponectin-mediated
activation of endothelial nitric-oxide synthase. J Biol Chem 2009;
 Poehls J, Wassel CL, Harris TB, et al. Association of adiponectin
with mortality in older adults: the Health, Aging, and Body Com-
position Study. Diabetologia 2009 [Epub ahead of print].
 Fawzia A Fahim, Mady EA. Antitumor activities of iodoacetate
and dimethylsulphoxide against solid Ehrlich Carcinoma growth in
mice. Biol Res 2003; 36 (2): 253-62.
 Siddiqui NI. Incretin mimetics and DPP-4 inhibitors: new approach
to treatment of type 2 diabetes mellitus. Mymensingh Med J 2009;
 Karra E, Chandarana K, Batterham RL. The role of peptide YY in
appetite regulation and obesity. J Physiol 2009; 587(Pt 1): 19-25.
Calorie Restriction Mimetics Open Longevity Science, 2009, Volume 3 21
 Minor RK, Chang JW, de Cabo R. Hungry for life: How the arcu-
ate nucleus and neuropeptide Y may play a critical role in mediat-
ing the benefits of calorie restriction. Mol Cell Endocrinol 2009;
 Wei M, Fabrizio P, Hu J, et al. Life span extension by calorie re-
striction depends on Rim15 and transcription factors downstream
of Ras/PKA, Tor, and Sch9. PLoS Genet 2008; 4(1): e13.
 Tachibana T, Mori M, Khan MS, Ueda H, Sugahara K, Hiramatsu
K. Central administration of galanin stimulates feeding behavior in
chicks. Comp Biochem Physiol A Mol Integr Physiol 2008 [Epub
ahead of print].
 Vrontakis ME. Galanin: a biologically active peptide. Curr Drug
Targets CNS Neurol Disord 2002; 1(6): 531-41.
 Caldeira da Silva CC, Cerqueira FM, Barbosa LF, Medeiros MH,
Kowaltowski AJ. Mild mitochondrial uncoupling in mice affects
energy metabolism, redox balance and longevity. Aging Cell 2008;
 Jonas WB, Ives JA. Should we explore the clinical utility of hor-
mesis? Hum Exp Toxicol 2008; 27(2): 123-7.
 Kyriazis M. Clinical anti-aging hormetic strategies. Rejuvenation
Res 2005; 8(2): 96-100.
 Honjoh S, Yamamoto T, Uno M, Nishida E. Signalling through
RHEB-1 mediates intermittent fasting-induced longevity in C. ele-
gans. Nature 2009; 457(7230): 726-30.
Received: April 22, 2009 Revised: May 14, 2009 Accepted: October 05, 2009
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