Proc Natl Acad Sci U S A 2006 May 16; 103(20): 7901-5 (Read article online)

Bonkowski MS, Rocha JS, Masternak MM, Al Regaiey KA, Bartke A

Reduced intake of nutrients [calorie restriction (CR)] extends longevity in organisms ranging from yeast to mammals. Mutations affecting somatotropic, insulin, or homologous signaling pathways can increase life span in worms, flies, and mice, and there is considerable evidence that reduced secretion of insulin-like growth factor I and insulin are among the mechanisms that mediate the effects of CR on aging and longevity in mammals. In the present study, mice with targeted disruption of the growth hormone (GH) receptor [GH receptor/GH-binding protein knockout (GHRKO) mice] and their normal siblings were fed ad libitum (AL) or subjected to 30% CR starting at 2 months of age. In normal females and males, CR produced the expected increases in overall, average, median, and maximal life span. Longevity of normal mice subjected to CR resembles that of GHRKO animals fed AL. In sharp contrast to its effects in normal mice, CR failed to increase overall, median, or average life span in GHRKO mice and increased maximal life span only in females. In a separate group of animals, CR for 1 year improved insulin sensitivity in normal mice but failed to further enhance the remarkable insulin sensitivity in GHRKO mutants. These data imply that somatotropic signaling is critically important not only in the control of aging and longevity under conditions of unlimited food supply but also in mediating the effects of CR on life span. The present findings also support the notion that enhanced sensitivity to insulin plays a prominent role in the actions of CR and GH resistance on longevity.

Ageing Res Rev 2006 May 9; (Read article online)

Hyun DH, Hernandez JO, Mattson MP, de Cabo R

Oxidative stress over time leads to the accumulation of damaged macromolecules and to profound physiological changes that are associated with several age-related diseases. The plasma membrane redox system (PMRS) appears to attenuate oxidative stress acting as a compensatory mechanism during the aging process. The PMRS appears to play a protective role during mitochondrial dysfunction to provide cells with a survival mechanism by lowering oxidative stress. The PMRS accomplishes this by producing more NAD(+) for glycolytic ATP production via transfer of electrons from intracellular reducing equivalents to extracelluar acceptors. Ubiquinone and alpha-tocopherol are key antioxidant molecules in the plasma membrane that are affected by aging and can be up-regulated by dietary interventions such as calorie restriction (CR). Up-regulation of PMRS activity leads to cell survival and membrane homeostasis under stress conditions and during calorie restriction. Further studies of the PMRS may provide not only additional information on the mechanisms involved in aging and CR, but may provide therapeutic targets for the prevention and treatment of age-related diseases.

Proc Natl Acad Sci U S A 2006 May 8; (Read article online)

Bonkowski MS, Rocha JS, Masternak MM, Al Regaiey KA, Bartke A

Reduced intake of nutrients [calorie restriction (CR)] extends longevity in organisms ranging from yeast to mammals. Mutations affecting somatotropic, insulin, or homologous signaling pathways can increase life span in worms, flies, and mice, and there is considerable evidence that reduced secretion of insulin-like growth factor I and insulin are among the mechanisms that mediate the effects of CR on aging and longevity in mammals. In the present study, mice with targeted disruption of the growth hormone (GH) receptor [GH receptor/GH-binding protein knockout (GHRKO) mice] and their normal siblings were fed ad libitum (AL) or subjected to 30% CR starting at 2 months of age. In normal females and males, CR produced the expected increases in overall, average, median, and maximal life span. Longevity of normal mice subjected to CR resembles that of GHRKO animals fed AL. In sharp contrast to its effects in normal mice, CR failed to increase overall, median, or average life span in GHRKO mice and increased maximal life span only in females. In a separate group of animals, CR for 1 year improved insulin sensitivity in normal mice but failed to further enhance the remarkable insulin sensitivity in GHRKO mutants. These data imply that somatotropic signaling is critically important not only in the control of aging and longevity under conditions of unlimited food supply but also in mediating the effects of CR on life span. The present findings also support the notion that enhanced sensitivity to insulin plays a prominent role in the actions of CR and GH resistance on longevity.

J Am Geriatr Soc 2006 Apr; 54(4): 648-53 (Read article online)

Yukawa M, Cummings DE, Matthys CC, Callahan HS, Frayo RS, Spiekerman CF, Weigle DS

OBJECTIVES: To determine whether the failure of the orexigenic hormone ghrelin to increase as it normally does with weight loss contributes to impaired weight recovery in older persons. DESIGN: Prospective diet intervention study. SETTING: University of Washington Medical Center from 2001 through 2005. PARTICIPANTS: Twenty-one younger (18-35) and 18 older (>/=70) men and women. INTERVENTION: Two weeks of a weight-maintaining diet were followed in sequence by 2 weeks of 30% calorie restriction, then 4 weeks of ad libitum food intake. MEASUREMENTS: Twenty-four-hour plasma ghrelin levels, dual x-ray absorptiometry scan for body composition, resting energy expenditure, and calorie intakes were measured. RESULTS: Both younger and older subjects lost weight with calorie restriction and failed to fully regain their baseline weight. The older adults trended toward increasing their calorie intake above their baseline level during the ad libitum period (111+/-66 kcal, P=.11), whereas the younger individuals did not (-236+/-95 kcal, P=.02). There was no statistically significant difference between the two cohorts in 24-hour ghrelin levels before or after calorie restriction. Ghrelin levels in the two cohorts increased equivalently after calorie restriction and decreased after ad libitum food consumption resumed. CONCLUSION: Ghrelin levels in healthy older individuals respond appropriately in a compensatory manner to changes in body weight and calorie intake.

Antioxid Redox Signal 2006 Mar-Apr; 8(3-4): 529-38 (Read article online)

Seo AY, Hofer T, Sung B, Judge S, Chung HY, Leeuwenburgh C

Hepatic aging may involve alterations in redox status, resulting in enhanced oxidant production and changes in specific signaling pathways that lead to a pro-inflammatory response. The authors investigated whether mild calorie restriction and long-term voluntary exercise could attenuate these changes. Four groups of male Fischer 344 rats were compared: young (6 mo), old (24 mo), old calorie restricted (8% CR, 24 mo) and old CR with daily voluntary wheel running (Exercise; 8% CR, 24 mo). Levels of endogenous reactive oxygen species (ROS), nitric oxide (NO(.)), and peroxynitrite (ONOO()) were significantly higher in the old ad libitum fed group compared to the young group. Sulfhydryl (-SH) content was significantly reduced and glutathione (GSH) content tended to be lower in the old animals. Old rats had significantly increased nuclear presence of NF-kappaB and in connection, increased levels of regulatory cytosolic phosphorylated I-kappaBalpha and decreased dephosphorylated I-kappaBalpha, suggesting an increased inflammatory response. Interestingly, a significant increase in liver RNA oxidation (8-oxo-7,8-dihydroguanosine) in the old ad libitum fed rats was detected and DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine) tended to be increased. The age-associated increase in oxidative stress and upregulation of pro-inflammatory proteins was attenuated in the livers from both the CR and the exercise + CR groups.

Biogerontology 2006 May 5; (Read article online)

Holliday R

Some animals live in environments in which the food supply fluctuates. When it is scarce these animals do not breed, but invest resources into survival until food is again available, and they can reproduce. Under these circumstances the lifespan can be increased, just as it is after calorie restriction. Other animals have a fairly constant food supply, and it is predicted that these would not have an extended life span if subjected to calorie restriction. Hibernation is a natural form of calorie restriction, and in some cases may lengthen lifespan.

Antioxid Redox Signal 2006 Mar-Apr; 8(3-4): 671-80 (Read article online)

Jung KJ, Maruyama N, Ishigami A, Yu BP, Chung HY

It was recently found that age-related changes in SMP30 expression can be modulated by antioxidative action. In the current study, the modulation of SMP30 gene expression was explored by (a) antioxidative calorie restriction (CR), (b) proinflammatory lipopolysaccharide (LPS), in aged rat, (c) oxidative stress promoter, tert-butylhydroperoxide (t-BHP)-injected mouse, and (d) t-BHP-treated Ac2F cells. Utilizing EMSA, particular attention was given to the binding activity of unidentified transcription factor in sites 3 and 5 that are located in -800 bp of the SMP30 promoter. Results showed that CR prevented the age-related decrease in SMP30 expression, and also showed that SMP30 gene expression and binding activities of sites 3 and 5 decreased with treatments of t-BHP or LPS. These findings were confirmed by the antioxidant NAC and ERK-specific inhibitor PD098059 that blunted decreased SMP30 gene expression and binding activity of sites 3 and 5 by t-BHP in Ac2F cell system. Our data strongly indicate that the SMP30 transcriptional process is redox-sensitive and its modulation occurs at DNA binding sites 3 and 5 in the promoter region. Perhaps a more significant finding of the present study is that the downregulation of SMP30 is likely involved in ERK signal pathway.

Biogerontology 2006 May 5; (Read article online)

Yu BP

Experimentally imposed calorie restriction (CR) is shown to result in the most reproducible endpoint of lifespan extension in all animals models tested. In this presentation, the question of CR's effect on human longevity is reviewed by discussing data pertinent to the putative efficacy of CR on humans. Arguments are presented in support of this possibility based on CR's unique abilities to retard biological functional declines and to deter pathological processes, both of which are major targets of deleterious oxidative stress. To delineate the cellular and molecular mechanisms of CR's efficacy on human longevity, this review elaborates on the modulation of CR on the inflammatory process, a common risk factor for many chronic diseases. Discussions also include evidence from human data on the effect of CR in the loss of body weight, known to suppress inflammatory cytokines, subsequently leading to the reduction of chronic diseases known to compromise the functional longevity of humans.

Antioxid Redox Signal 2006 Mar-Apr; 8(3-4): 572-81 (Read article online)

Chung HY, Sung B, Jung KJ, Zou Y, Yu BP

Emerging pathological evidence indicates that major chronic aging-related diseases such as atherosclerosis, arthritis, dementia, osteoporosis, and cardiovascular diseases, are inflammation-related. In this review, inflammation is examined as a possible underlying basis for the molecular alterations that link aging and agerelated pathological processes. A proposal for the molecular inflammation hypothesis of the aging views the redox derangement that occurs during aging as the major factor for increased risk for age-related inflammation. Accumulated data strongly indicate the activation of redox-sensitive transcription factors and dysregulated gene expression under the age-related oxidative stress seems to be the major culprits. Key players involved in the inflammatory process are the age-related upregulation of NF-kappaB, IL-1beta, IL-6, TNFalpha, cyclooxygenase-2, adhesion molecules, and inducible NO synthase. Furthermore, data are presented on the molecular events involved in age-related NF-kappaB activation and phosphorylation by IkappaB kinase/NIK and MAPKs. Experimental data on antiaging calorie restriction (CR) for its antiinflammatory efficacy by suppressing the upregulated proinflammatory mediators will be reviewed. Also, the involvement of another super family of transcription factors, PPARs (PPARalpha, gamma) as regulators of proinflammatory responses and NF-kappaB signaling pathway is described as well as a discussion on the physiological significance of a well-maintained balance between NF-kappaB and PPARs.

Life Sci 2006 Apr 18; 78(21): 2523-2532 (Read article online)

Kim YJ, Kim HJ, No JK, Chung HY, Fernandes G

Inflammation, inflammatory mediators, cyclooxygenase (COX)-2, and inducible nitric oxide (iNOS) are all influenced by age-related oxidative status. To investigate the effect of dietary fish oil (FO) and calorie restriction (CR) on oxidative stress-related inflammatory status with age, (NZB/NZW) F1 (B/W) mice were fed for 4 and 9 months either ad libitum or calorie-restricted (60% of ad libitum intake) diets containing 5% corn oil or 5% FO. We measured several key oxidative and inflammatory markers: TBARS, xanthine oxidase (XOD)-derived superoxide generation, and PGE(2) and LTB(4) production. Expressions of renal COX-1, COX-2, and iNOS mRNA were analyzed by RT-PCR; additionally, COX-2 protein was estimated by Western-blot method. Results show that FO intake and CR individually and together suppressed age-related increases in lipid peroxidation and superoxide generation. The inhibitory effects of dietary FO and CR were also found for iNOS expression, COX-2 expression, which subsequently led to the suppression of PGE(2) and LTB(4). We conclude that the beneficial effects of FO feeding and CR are synergistic in ameliorating the age-related nephritis of B/W mice by suppressing COX-2 and iNOS, reactive species generation, and pro-inflammatory mediators.

Proc Natl Acad Sci U S A 2006 Feb 7; 103(6): 1768-73 (Read article online)

López-Lluch G, Hunt N, Jones B, Zhu M, Jamieson H, Hilmer S, Cascajo MV, Allard J, Ingram DK, Navas P, de Cabo R

Age-related accumulation of cellular damage and death has been linked to oxidative stress. Calorie restriction (CR) is the most robust, nongenetic intervention that increases lifespan and reduces the rate of aging in a variety of species. Mechanisms responsible for the antiaging effects of CR remain uncertain, but reduction of oxidative stress within mitochondria remains a major focus of research. CR is hypothesized to decrease mitochondrial electron flow and proton leaks to attenuate damage caused by reactive oxygen species. We have focused our research on a related, but different, antiaging mechanism of CR. Specifically, using both in vivo and in vitro analyses, we report that CR reduces oxidative stress at the same time that it stimulates the proliferation of mitochondria through a peroxisome proliferation-activated receptor coactivator 1 alpha signaling pathway. Moreover, mitochondria under CR conditions show less oxygen consumption, reduce membrane potential, and generate less reactive oxygen species than controls, but remarkably they are able to maintain their critical ATP production. In effect, CR can induce a peroxisome proliferation-activated receptor coactivator 1 alpha-dependent increase in mitochondria capable of efficient and balanced bioenergetics to reduce oxidative stress and attenuate age-dependent endogenous oxidative damage.

Biochem J 2006 Apr 21; (Read article online)

Zhang J

Resveratrol mimics calorie restriction to extend lifespan of C. elegans, yeast and Drosophila, possibly through activation of Sir2, a NAD-dependent histone deacetylase. In this study, resveratrol is shown to inhibit insulin signaling pathway in several cell lines and rat primary hepatocytes in addition to its broad spectrum inhibitions of several signaling pathways. Resveratrol effectively inhibits insulin-induced AKT and MAPK activation mainly through disruption of the interactions between insulin receptor substrates and its downstream binding proteins including p85 regulatory subunit of PI-3 kinase and Grb2. The inhibitory effect of resveratrol on insulin signaling is also demonstrated at mRNA level, where resveratrol reverses insulin effects on Phosphoenoylpyruvate carboxykinase (PEPCK), Glucose-6-Phosphatase (G-6-Pase), Fatty acid synthase (FAS) and Glucokinase (GK). In addition, RNAi experiment shows that the inhibitory effect of resveratrol on insulin signaling pathway is not weakened in cells with reduced expression of SirT1, the mammalian counterpart of Sir2. These observations raise the possibility that resveratrol may additionally modulate lifespan through inhibition of insulin signaling pathway, independently of its activation of SirT1 histone deacetylase. Furthermore, this study may help explain a wide range of biological effects of resveratrol, and provides further insight into the molecular basis of calorie restriction.

Med Hypotheses 2006 Mar 8; (Read article online)

Johnson JB, Laub DR, John S

Restricting caloric intake to 60-70% of normal adult weight maintenance requirement prolongs lifespan 30-50% and confers near perfect health across a broad range of species. Every other day feeding produces similar effects in rodents, and profound beneficial physiologic changes have been demonstrated in the absence of weight loss in ob/ob mice. Since May 2003 we have experimented with alternate day calorie restriction, one day consuming 20-50% of estimated daily caloric requirement and the next day ad lib eating, and have observed health benefits starting in as little as two weeks, in insulin resistance, asthma, seasonal allergies, infectious diseases of viral, bacterial and fungal origin (viral URI, recurrent bacterial tonsillitis, chronic sinusitis, periodontal disease), autoimmune disorder (rheumatoid arthritis), osteoarthritis, symptoms due to CNS inflammatory lesions (Tourette's, Meniere's) cardiac arrhythmias (PVCs, atrial fibrillation), menopause related hot flashes. We hypothesize that other many conditions would be delayed, prevented or improved, including Alzheimer's, Parkinson's, multiple sclerosis, brain injury due to thrombotic stroke atherosclerosis, NIDDM, congestive heart failure. Our hypothesis is supported by an article from 1957 in the Spanish medical literature which due to a translation error has been construed by several authors to be the only existing example of calorie restriction with good nutrition. We contend for reasons cited that there was no reduction in calories overall, but that the subjects were eating, on alternate days, either 900 calories or 2300 calories, averaging 1600, and that body weight was maintained. Thus they consumed either 56% or 144% of daily caloric requirement. The subjects were in a residence for old people, and all were in perfect health and over 65. Over three years, there were 6 deaths among 60 study subjects and 13 deaths among 60 ad lib-fed controls, non-significant difference. Study subjects were in hospital 123 days, controls 219, highly significant difference. We believe widespread use of this pattern of eating could impact influenza epidemics and other communicable diseases by improving resistance to infection. In addition to the health effects, this pattern of eating has proven to be a good method of weight control, and we are continuing to study the process in conjunction with the NIH.

Aging Cell 2006 Apr; 5(2): 97-108 (Read article online)

Ingram DK, Zhu M, Mamczarz J, Zou S, Lane MA, Roth GS, deCabo R

When considering all possible aging interventions evaluated to date, it is clear that calorie restriction (CR) remains the most robust. Studies in numerous species have demonstrated that reduction of calories 30-50% below ad libitum levels of a nutritious diet can increase lifespan, reduce the incidence and delay the onset of age-related diseases, improve stress resistance, and decelerate functional decline. A current major focus of this research area is whether this nutritional intervention is relevant to human aging. Evidence emerging from studies in rhesus monkeys suggests that their response to CR parallels that observed in rodents. To assess CR effects in humans, clinical trials have been initiated. However, even if results from these studies could eventually substantiate CR as an effective pro-longevity strategy for humans, the utility of this intervention would be hampered because of the degree and length of restriction required. As an alternative strategy, new research has focused on the development of 'CR mimetics'. The objective of this strategy is to identify compounds that mimic CR effects by targeting metabolic and stress response pathways affected by CR, but without actually restricting caloric intake. For example, drugs that inhibit glycolysis (2-deoxyglucose), enhance insulin action (metformin), or affect stress signaling pathways (resveratrol), are being assessed as CR mimetics (CRM). Promising results have emerged from initial studies regarding physiological responses which resemble those observed in CR (e.g. reduced body temperature and plasma insulin) as well as protection against neurotoxicity (e.g. enhanced dopamine action and up-regulated neurotrophic factors). Ultimately, lifespan analyses in addition to expanded toxicity studies must be accomplished to fully assess the potential of any CRM. Nonetheless, this strategy clearly offers a very promising and expanding research endeavor.

Am J Physiol Endocrinol Metab 2006 Jan 31; (Read article online)

Nadeau KJ, Ehlers LB, Aguirre LE, Moore RL, Jew KN, Ortmeyer HK, Hansen BC, Reusch JE, Draznin B

Intramuscular triglyceride (IMTG) deposition in skeletal muscle is associated with obesity and type 2 diabetes (T2DM), and thought to be related to insulin resistance (IR). Curiously, despite enhanced skeletal muscle insulin sensitivity, highly-trained athletes and calorie-restricted (CR) monkeys also have increased IMTG. Sterol regulatory element binding proteins (SREBP) are transcription factors that regulate the biosynthesis of cholesterol and fatty acids. SREBP-1 is increased by insulin in skeletal muscle in vitro, and in skeletal muscle of IR subjects, but SREBP-1 expression has not been examined in exercise training or CR. We examined the relationship between IMTG and SREBP-1 expression in animal models of exercise and CR. Methods/Results: Gastrocnemius and soleus muscle biopsies were obtained from 38 Sprague Dawley rats (18 control and 20 exercise-trained). Triglyceride content was higher in the gastrocnemius and soleus muscles of the trained rats. SREBP-1c mRNA, SREBP-1 precursor and mature proteins, and fatty acid synthase (FAS) protein were increased with exercise training. Monkeys (Macacca mulatta) were CR for a mean of 10.4 years, preventing weight gain and IR. Vastus lateralis muscle was obtained from 12 monkeys (6 CR and 6 controls). SREBP-1 precursor and mature proteins, and FAS protein were higher in the CR monkeys. In addition, phosphorylation of ERK1/ERK2 was increased in skeletal muscle of CR animals. Summary: SREBP-1 protein and SREBP-1c mRNA are increased in interventions that increase IMTG, despite enhanced insulin sensitivity. CR and exercise-induced augmentation of SREBP-1 expression may be responsible for the increased IMTG seen in skeletal muscle of highly conditioned athletes.

Obesity (Silver Spring) 2006 Jan; 14(1): 115-21 (Read article online)

Martin CK, O'Neil PM, Pawlow L

OBJECTIVE: This study examined food cravings during a primarily food-based low-calorie diet (LCD) and a supplement-based very-LCD (VLCD). RESEARCH METHODS AND PROCEDURES: The Food Craving Inventory (FCI) was used to measure general cravings and cravings for specific types of foods (sweets, high fats, carbohydrates/starches, and fast food fats). The FCI was completed by participants in the LCD and VLCD programs at baseline and after 11 weeks of dieting. The VLCD group also completed the FCI at Week 6 and after 5 weeks of a refeeding phase, when their diet consisted primarily of solid food. RESULTS: From baseline to Week 12, craving decreases were greater for the VLCD group than for the LCD group on all measures. All craving measures decreased significantly for the VLCD group. The LCD group experienced a marginally significant decrease in sweet cravings. Within the VLCD group, all craving measures decreased significantly by Week 6 and did not change thereafter, including after resumption of solid food intake, and craving scores during all dieting points were lower than baseline. Changes in cravings were not related to weight loss. DISCUSSION: Cravings did not increase during either diet; all changes represented decreases. Compared with a primarily food-based diet (LCD), a more restrictive supplement-based diet (VLCD) resulted in significantly larger decreases in food cravings that occurred by the end of the 5th week of supplement use and did not rebound with resumption of solid food intake. The results of this study suggest that food cravings diminish with calorie restriction.

Int J Obes (Lond) 2006 Apr 4; (Read article online)

Jang Y, Kim OY, Lee JH, Koh SJ, Chae JS, Kim JY, Park S, Cho H, Lee JE, Ordovas JM

Objective:Perilipin (PLIN) is a class of protein-coating lipid droplets in adipocytes. We aimed to examine the association between common single-nucleotide polymorphisms (SNPs) at PLIN locus with circulating free fatty acid (FFA) and abdominal fat distribution in response to weight loss.Methods:Non-diabetic/overweight-obese Koreans (n=177) participated in a 12-week calorie restriction (-300kcal/day) program. Seven SNPs (6209T>C, 10076C>G, 10171A>T, 11482G>A, 13042A>G, 13048C>T and 14995A>T), abdominal fat areas (visceral/subcutaneous fat areas at 1st lumbar and 4th lumbar levels), serum lipids, glucose, insulin, FFA, oxidized low-density lipoprotein (LDL) and urinary 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) were examined.Results:Single-nucleotide polymorphisms 10076C>G/10171A>T showed the strongest positive linkage disequilibrium (LD) (D'=0.923, R (2)=0.839, P<0.001) and SNPs11482G>A/14995A>T showed moderate positive LD (D'=0.824, R (2)=0.578, P<0.001). Calorie restriction induced 4.6% weight loss with significant abdominal fat reduction. In response to weight loss, subjects with nCA/nCA haplotypes at SNPs 10076C>G/10171A>T showed greater reduction in FFA levels than those with CA/CA haplotype (CA/CA: C/C at SNP 10076 and A/A at SNP 10171, nCA: non-CA haplotype carrier). On the other hand, subjects with nGA/nGA haplotype at SNPs 11482G>A/14995A>T had increased FFA levels with a rapid loss in abdominal fat, whereas GA/GA haplotype carriers had reduction in FFA levels. These results still remained significant after adjusting for age, gender and BMI. Prostaglandin F(2alpha) and oxidized LDL were also more reduced in GA/GA haplotype carriers than in nGA haplotype carriers. This effect remained significant after adjusting for baseline level, age, gender and BMI. Paradoxically, nGA haplotype carriers had increased levels of urinary PGF(2alpha) after weight reduction.Conclusion:Fasting plasma FFA changes following a modest weight loss in overweight-obese subjects are influenced by the genetic variability at the PLIN locus. Furthermore, circulating FFA changes rather than body fat itself may determine changes in lipid peroxides such as urinary PGF(2alpha) and oxidized LDL.International Journal of Obesity advance online publication, 4 April 2006; doi:10.1038/sj.ijo.0803312.

Thromb Res 2006 Feb 7; (Read article online)

Murakami T, Horigome H, Tanaka K, Nakata Y, Ohkawara K, Katayama Y, Matsui A

INTRODUCTION: Generation of platelet-derived microparticle (PMP) is implicated in cardiovascular disease (CVD). However, the influence of adiposity and weight reduction on PMP generation remains to be fully elucidated. We compared PMP generation and fibrinolytic parameters between 49 non-diabetic obese (obese group) and 37 age-matched non-obese subjects (control group), and compared the effects of weight reduction on the parameters between a 12-week calorie restricted diet and diet with aerobic exercise in obese subjects. MATERIALS AND METHODS: PMP, plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) antigen were measured before and after intervention. RESULTS: Before intervention, PMP, PAI-1 activity and t-PA antigen values were elevated in the obese group compared with the control group. In all 86 subjects of both groups, these three parameters correlated with body mass index, waist circumference and fat tissue mass. There was a positive correlation between plasma levels of fibrinolytic parameters and visceral fat area (VFA). PMP values correlated with subcutaneous fat area (SFA). The intervention significantly reduced PMP, PAI-1 activity and t-PA antigen levels. There was a significant correlation between percentages of changes in PMP values and those in BMI, fat tissue mass and VFA in the obese group. No additional effect of exercise on PMP or fibrinolytic parameters was observed. CONCLUSIONS: Overproduction of PMP and fibrinolytic abnormalities may be associated with excessive adipose tissue. Weight reduction by either calorie restriction with or without exercise improves fibrinolytic abnormalities and PMP overproduction, probably through reduction of adipose tissue.

J Am Assoc Lab Anim Sci 2006 Jan; 45(1): 40-7 (Read article online)

Gerdes R, Fieber LA

Although the California sea hare, Aplysia californica, is well known from neurobiological studies and is raised in the laboratory for this purpose, various aspects of its life history in the laboratory, such as aging dynamics, are unknown. Therefore we collected life history data on 4 cohorts of eggs from hatchery-reared animals and performed an actuarial analysis of mortality data. Temperature was controlled at 13 to 15 degrees C, the photoperiod was a 14:10-h light:dark cycle, and the seawater O2 concentration, pH, and salinity were held at optimized levels. The feeding protocol for 3 cohorts was unrestricted access to the red macroalga Gracilaria ferox, whereas the remaining cohort was fed standard hatchery rations of G. ferox 4 times per week. Growth was sigmoidal in each cohort and resulted in linear growth rates of 1.25 to 3.62 g/d during the exponential phase; these rates were not influenced by feeding level. Sexual maturity occurred at approximately 160 g, at ages ranging from 144 to 241 d. Egg production was highly variable in the different cohorts. Mean lifespan of cohorts fed ad libitum was approximately 228 d. In contrast, the cohort fed standard rations lived an average of 375 d and showed a lower initial mortality rate, suggesting that calorie restriction on a single-species diet prolongs lifespan in California sea hares.

Ageing Res Rev 2006 Apr 24; (Read article online)

Hunt ND, Hyun DH, Allard JS, Minor RK, Mattson MP, Ingram DK, de Cabo R

Aging is a physiological process that involves a multi-factorial set of deleterious changes. These alterations are caused by an exponential increase in damage to macromolecules. This process is likely due to the cumulative effects of oxidative stress over time. One area of ongoing research in gerontology has focused on determining why there is an age-dependent decrease in cellular bioenergetics. The aim of this review is to summarize the recent findings on the effects of aging and calorie restriction on energy metabolism. The effect of calorie restriction on age-associated changes in bioenergetic parameters will be examined.