Biomarkers of Caloric Restriction May Predict Longevity in Humans

Roth, George S.; Lane, Mark A.; Ingram, Donald K.; Mattison, Julie A.; Elahi, Dariush; Tobin, Jordan D.; Muller, Denis C.; Metter, E. Jeffrey

doi:10.1126/science.1071851

Cited by 377 publications

(274 citation statements)

References 5 publications

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“…The age-related changes in plasma testosterone, triglycerides, oxidative damage and glucose regulation could be attenuated by CR, 37,38 which is related to autophagic activation. 39 Sitzmann et al 40 reported that moderate CR could help maintain higher levels of circulating testosterone.…”

Section: Discussionmentioning

confidence: 95%

Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

Li¹,

Chen²,

Chen³

et al. 2011

Asian J Androl

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Late-onset hypogonadism (LOH) is closely related to secondary androgen deficiency in aged males, but the mechanism remains unclear. In this study, we found that reduced testosterone production in aged rat Leydig cells is associated with decreased autophagic activity. Primary rat Leydig cells and the TM3 mouse Leydig cell line were used to study the effect of autophagic deficiency on Leydig cell testosterone production. In Leydig cells from young and aged rats, treatment with wortmannin, an autophagy inhibitor, inhibited luteinising hormone (LH)-stimulated steroidogenic acute regulatory (StAR) protein expression and decreased testosterone production. In contrast, treatment with rapamycin, an autophagy activator, enhanced LH-stimulated steroidogenesis in Leydig cells from aged, but not young, rats. Intracellular reactive oxygen species (ROS) levels were increased in both young and aged Leydig cells treated with wortmannin but decreased only in aged Leydig cells treated with rapamycin. Furthermore, an increased level of ROS, induced by H 2 O 2 , resulted in LH-stimulated steroidogenic inhibition. Finally, knockdown of Beclin 1 decreased LH-stimulated StAR expression and testosterone production in TM3 mouse Leydig cells, which were associated with increased intracellular ROS level. These results suggested that autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells, which might be influenced by intracellular ROS levels.

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Section: Discussionmentioning

confidence: 95%

Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

Li¹,

Chen²,

Chen³

et al. 2011

Asian J Androl

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“…It seems that HCRs are good candidates supporting the 'uncoupling to 489 survive' hypothesis since their higher OXPHOS, PGC-1 and UCP2 levels combined with 490 higher thermogenesis and longer lifespan compared to LCRs , 491 Karvinen et al 2015. 492 493 Previous studies have also shown that core body temperature declines with age both in 494 rodents and in humans , Roth et al 2002, Sanchez-Alavez, Alboni 495 & Conti 2011, which has raised speculation of possible anti-ageing effects of low body 496 temperature. In our studies, HCRs in the control group had lower body temperature at the age 497 of 21 months than HCR-Rs, and our previous study reported that HCRs in control group had 498 also longer lifespan (Karvinen et al 2015).…”

Section: Voluntary Running Aids To Maintain High Thermo-genesis Inmentioning

confidence: 99%

“…Previous studies have also shown that core body temperature declines with age both in rodents and in humans Roth et al 2002;, which has raised speculation of possible anti-ageing effects of low body temperature. In our studies, HCRs in the control group had lower body temperature at the 21-month time point than HCR-Rs, and this was accompanied with longer lifespan (Figures 15B, 18).…”

Section: Thermogenesismentioning

confidence: 99%

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

Karvinen

Silvennoinen

Vainio

et al. 2016

Experimental Gerontology

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“…From a 27-year communitybased cohort study of Japanese men, serum dehydroepiandrosterone sulfate was found to be a good predictor of longevity (Enomoto et al 2008). Roth and colleagues (Roth et al 2002) have identified insulin and body temperature as robust biomarkers of calorie restriction, a treatment known to increase life span in a number of animal models. Thus far, however, we have not been able to utilize these biomarkers to identify individuals that will live a longer and healthier life.…”

Section: Introductionmentioning

confidence: 99%

Development of a serum profile for healthy aging

Byerley

Leamy

Tam

et al. 2010

AGE

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Increasing numbers of Americans are reaching 85 years of age or older, yet there are no reliable biomarkers to predict who will live this long. The goal of this pilot study therefore was: (1) to identify a potential serum pattern that could identify proteins involved in longevity and (2) to determine if this pattern was a marker of longevity in an independent sample of individuals. Serum samples were analyzed in three cohorts of individuals (n=12 in each) aged 20-34, 60-74, and Q90 years who participated in The Louisiana Healthy Aging Study.The 12 most abundant proteins were removed and the remaining proteins separated by two-dimensional gel electrophoresis. Gels were matched and the intensity of each spot quantified. Multivariate discriminant analysis was used to identify a serum pattern that could separate these three age cohorts. Seven protein spots were found that correctly distinguished the subjects into the three groups. However, these spots were not as successful in discriminating the ages in a second set of 15 individuals as only eight of these subjects were placed into their correct group. These preliminary results show that the proteomics approach can be used to identify potential proteins or markers that may be involved in the aging process and/or be important determinants of longevity.

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Biomarkers of Caloric Restriction May Predict Longevity in Humans

Cited by 377 publications

References 5 publications

Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

Development of a serum profile for healthy aging

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