CR-RNA: Can Calorie Restriction affect blood miRNAs and mRNAs?

[Meredith Averill]

Here’s your chance to contribute to CR Science by contributing lab samples!

Participants’ blood and urine will be sampled to study micro-RNAs and messenger RNAs.

Differences between these genetic components in calorie restrictors and control volunteers will be analyzed.

 

Eligibility Requirements:

• 
   
  Experienced Calorie Restrictor
  Good health – no known illness
  30 to 75 years of age
  110 pounds in weight, minimum
  Male (We’ll let the men blaze the trail -- with the goal of studying women soon.)
  

 

• 
   
  
• The study involves a one-time collection of a small amount of blood.
  
• Procedure includes: venipuncture (blood draw)
  
• All procedures will be performed under the supervision of trained professionals at the UCR campus health clinic or another accredited clinical laboratory.
  
• Participants will be reimbursed for their travel expenses.
  
• If you are interested in participating in the CR cohort, please contact Meredith Averill at boardchair@CRSociety.org.
  

Researchers: Joseph Dhahbi, MD, PhD; Stephen Spindler, PhD

Department of Biochemistry, University of California, Riverside

[davebtokyo]

Meredith,

 

I thought Al's post of the 11th on MiRNAs very interesting, (appended below) and wondered whether it had any bearing on

the CR-RNA research.

 

Dave

 

It seems that http://en.wikipedia.org/wiki/Fibrosis may matter much for microRNA-21 action, based on:

 

http://www.ncbi.nlm....med?term=MiR-21 (C-reactive protein OR fibrinogen OR TGF) AND pubmed pmc local[sb] AND loprovpmc[sb]

 

The below paper is pdf-availed. Figures can be seen in the URL version.

Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammagingOlivieri F, Spazzafumo L, Santini G, Lazzarini R, Albertini MC, Rippo MR, Galeazzi R, Abbatecola AM, Marcheselli F, Monti D, Ostan R, Cevenini E, Antonicelli R, Franceschi C, Procopio AD

Mech Ageing Dev. 2012 Oct 2. pii: S0047-6374(12)00160-1. doi: 10.1016/j.mad.2012.09.004. [Epub ahead of print]

PMID: 23041385http://www.sciencedi...047637412001601Abstract

Circulating microRNAs (miRs) have been investigated as diagnostic/prognostic biomarkers in human diseases. However, little is known about their expression throughout the aging process.

Eleven healthy individuals aged 20, 80 and 100 years underwent miR plasma profiling. The validation cohort consisted of 111 healthy adults (CTR) aged 20-105 years and included 30 centenarians. In addition, 34 patients with cardiovascular disease (CVD) and 15 healthy centenarian offspring (CO) were enrolled

An Exploratory Factorial Analysis grouped the miRs into three main factors: factor 1 primarily higher in 20-year-old subjects, but these differences did not reach statistical significance, factor 2 primarily higher in octogenarians and factor 3 primarily higher in centenarians. MiR-21, the most highly expressed miR of factors 2 and 3, was further validated, confirming the differences in the age-groups. MiR-21 expression was higher in the CVD patients and lower in the CO compared to the age-matched CTR. MiR-21 was correlated with C-reactive protein and fibrinogen levels. TGF-ß signaling was the predicted common pathway targeted by miRs of factor 2 and 3. TGF-ßR2 mRNA, a validated miR-21 target, showed the highest espression in the leukocytes from a subset of the octogenarians.

Our findings suggest that miR-21 may be a new biomarker of inflammation.

Highlights

Profiling of circulating miRs revealed age-related differences.

MiR-21 was decreased in centenarians and increased in CVD patients.

A significant correlation between miR-21 and C-reactive protein and fibrinogen was observed

MiR-21 appears as circulating biomarker of inflammation in aging process and CVD.

Keywords

Circulating microRNA; Centenarians; Centenarians offspring; Circulating miR-21

1. Introduction

Human aging is a highly complex process characterized by the remodeling of many molecular pathways involved in cellular and tissue homeostasis ( [spazzafumo et al., 2011] and [Cevenini et al., 2010]).

An important goal in this field of research is to identify innovative cellular and tissue level biomarkers of aging that may also be useful for diagnosing age-related diseases.MicroRNAs (miRs) are small non-coding RNAs involved in the epigenetic regulation of coding gene expression. They provide an additional level of control for important cellular processes such as growth, differentiation, the stress response and remodeling ( [Garzon et al., 2009] and [Zampetaki et al., 2011]). They can safeguard the robustness of biological systems, modulating in turn the chance to achieve longevity or develop age-related diseases. Several recent reports have suggested that circulating miRs have relevant diagnostic and prognostic implications for age-related diseases, but their clinical relevance is still controversial ( [Cortez and Calin, 2009], [D’Alessandra et al., 2010], [Zampetaki et al., 2011], [Olivieri et al., 2012a] and [Olivieri et al., 2012b]). At present, only a few studies have identified significant differences in the circulating miR levels of healthy adults and centenarians (Elsharawy et al., 2012). Data obtained from models such as Caenorhabditis elegans and mouse have shown that specific miRs exhibit age-dependent expression patterns ( [Noren Hooten et al., 2010], [ibanez-Ventoso et al., 2006], [Li et al., 2011a] and [Maes et al., 2008]). It is important to recall that exceptional survival requires the dynamic maintenance of physiological variables at optimal levels and that the levels of many aging biomarkers have been shown to change throughout one's life ( [Yashin et al., 2009], [Franceschi et al., 2007] and [spazzafumo et al., 2011]). Interestingly, recent data have demonstrated that the expression of miRs in human peripheral blood mononuclear cells changes with aging, suggesting that miRs and their predicted targets may be potential diagnostic indicators of aging and/or age-related diseases ( [Noren Hooten et al., 2010] and [Li et al., 2011b]). Furthermore, gender specific signatures in the circulating miR profiles of young male and female individuals were recently reported (Duttagupta et al., 2011).

Studies have tested if lysed cells contribute to blood circulating miRs or if an active exchange of miRs occurs across cell membranes (microvesicles or exosomes) ( [Valadi et al., 2007], [Turchinovich et al., 2011] and [Ramachandran and Palanisamy, 2011]). An interesting aspect related to the “active secretory hypothesis” is the possibility that circulating miRs may influence the intercellular signaling of health status ( [Cocucci et al., 2009], [iguchi et al., 2010], [Zampetaki et al., 2011] and [Zhu and Fan, 2011]). It was recently demonstrated that exosomes are readily taken up by macrophages, supporting the notion that exosomal RNA can be shuttled between cells ( [Losche et al., 2004] and [Lasser et al., 2011]). Subpopulations of plasma microvesicles and their miRs have also been reported to regulate the immune response and hematopoiesis (Hunter et al., 2008). These findings underline the urgent need to investigate the biological role of circulating miRs

We aimed at identifying the plasma expression levels of miRs in differently aged healthy persons (20 to more than 100 years of age) to determine if healthy aging is characterized by differences in circulating miR expression levels. Moreover, because cellular miRs use well-connected networks to control many important biological functions, one may hypothesize that groups of miRs could modulate common target pathways. Therefore, we aimed at identifying the common pathways targeted by circulating miRs that are differentially expressed at different ages.

Finally, the circulating miRs that were differentially expressed in healthy subjects of different ages were also analyzed in older CVD patients and centenarian offspring. Geriatric CVD patients are one of the most studied models of unsuccessful aging, while centenarian offspring are a model of successful aging due to their significantly reduced risk of CVD development and mortality.

[snip]

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