Research Advances: Calorie Restriction and Increased Longevity

colleagues from Nestlé and Nestlé Purina Research centers in Switzerland and the United States point out that previous studies on a range of animals h...
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Chemical Education Today

Reports from Other Journals

Research Advances by Angela G. King

Calorie Restriction and Increased Longevity Linked to Metabolic Changes In a study of Labrador retriever dogs, those fed a calorierestricted diet showed different lifelong patterns relating to energy metabolism and the activities of their gut microbes and lived almost two years longer than similar dogs given a slightly higher-calorie diet. Imperial College London’s Jeremy K. Nicholson and colleagues from Nestlé and Nestlé Purina Research centers in Switzerland and the United States point out that previous studies on a range of animals have established caloric restriction as a proven method for extending the lifespan of animals. Those studies, however, have not explained how calorie restriction works. The new study, which followed 24 pairs of dogs lifelong, aimed at improving knowledge of the metabolic effects of caloric restriction, suggests that some of the important beneficial changes may relate to the activities of the symbiotic bacteria that live in the intestinal tract. Those microbes produce a range of biochemicals that may influence disease processes and alter energy metabolism in the host organism. Researchers paired 24 dogs, with one dog in each pair given 25 percent less food than the other. Those with a restricted intake of calories lived, on average, about 1.8 years longer than those with a greater

intake. Researchers noted that the study’s main goal was to help develop diets that keep pet animals alive and healthy for as long as possible, but that the findings may be relevant to human dietary changes and obesity. Nicholson’s team employed a 1H NMR-based metabonomic strategy to monitor urinary metabolic profiles throughout the dogs’ lifetimes (Figure 1). Metabonomics involves the study of multivariate responses of complex organisms to physiological and/or pathological stressors. The emerging patterns revealed that both age and caloric intake affected levels of metabolites in urine (see table below). For instance, creatinine and glycoprotein levels were age dependent, while energy-associated metabolites, such as creatine, lactate, acetate, and succinate, were depleted from the urine of dogs on the restricted diet. More Information 1. Wang, Yulan; Lawler, Dennis; Larson, Brian; Ramadan, Ziad; Kochhar, Sunil; Holmes, Elaine; Nicholson, Jeremy K. Metabonomic Investigations of Aging and Caloric Restriction in a Life-Long Dog

Changes of Metabolites Associated with Aging Chemical shift (ppm)

Figure 1. Three typical 600 MHz 1H NMR spectra of urine obtained from a dog with a control diet at ages (A) 13 weeks, (B) 1.5 yr, (C) 9 yr. Signals in the chemical shift range of d 6.5–9 and 0.7–3.0 are displayed at 4x magnification compared to signals in the d 3.0–4.5 range. Key: 1, a-ketobutyrate; 2, 2-propanol; 3, lactate; 4, alanine; 5, acetate; 6, 7, mixed N-acetylglycoproteins; 8, succinate; 9, citrate; 10, dimethylamine; 11, trimethylamine; 12, dimethylglycine; 13, creatinine; 14, taurine; 15, trimethylamine-N-oxide; 16, glycine; 17, (4-hydroxyphenyl)propionic acid; 18, (phenylacetyl)glycine; 19, Nmethylnicotinamide; 20, hippurate; 21, formate; 22, polyols. Image credits: Reprinted with permission from J. Proteome Research 2007, 6, 1846–1854. Copyright 2007 American Chemical Society.

13 weeks

alanine

d 1.48

acetate

d 1.924

NSD*

acetylglycoproteins

d 2.04

0.9308

citrate

d 2.55

NSD

NSD

1.5 years 10.3701 20.352 20.6026 NSD

creatinine

d 3.0465

20.4731

10.3796

DMA

d 2.724

0.942

20.5582

DMG

d 2.94

20.6631

NSD

9 years 10.3573 NSD 20.4087 10.3751 10.4175 NSD 10.6561

hippurate

d 7.831

20.3717

10.3043

NSD

3-HHPA

d 7.313(s)

20.6303

10.6004

NSD

a-ketobutyrate

d 1.07

20.7143

NSD

lactate

d 1.3285

NSD

20.2994

N-methyl­ nicotinamide

d 9.28

NSD

20.3221

10.7166 10.5904 NSD

2-propanol

d 1.1

succinate

d 2.41

NSD

TMA

d 2.88

NSD

TMAO

d 3.27

NSD

20.3949

NSD

taurine

d 3.437

NSD

10.5322

NSD

20.6932

10.5152 20.3448 NSD*

10.6485 10.3637 10.4594

1  indicates the increase in the concentration of metabolites. 2  indicates the decrease in the concentration of metabolites. *  NSD denotes no significant difference.

1242 Journal of Chemical Education  •  Vol. 84  No. 8  August 2007  •  www.JCE.DivCHED.org

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Reports from Other Journals Study. J. Proteome Res. 2007, 6, 1846–1854. Additional discussion of this paper is available online at http://pubs.acs.org/subscribe/journals/ jprobs/6/i05/html/0507profile1.html (accessed May 2007). 2. This Journal has published teaching labs on the synthesis of creatine and the detection of creatinine in urine. See J. Chem. Educ. 2006, 83, 1654 and 1983, 60, 74, respectively. 3. Nicholson’s research Web page can be found at http://www1. imperial.ac.uk/medicine/people/j.nicholson/ (accessed May 2007).

Isotope Ratios Reveal Trickery in the Produce Aisle The supermarket sign in the produce aisle says “organic” and the higher price lends credence. But is that organically grown fruit or vegetable authentic or a mislabeled version of some conventionally grown crop? Scientists in the United Kingdom are now reporting development of a test that could help answer that question. Simon D. Kelly and colleagues point out that authentication of organic food products at present is based on enforcement of production standards through certification and inspection—a paper trail from farm to fork. The basic framework that determines what produce is organic is governed by the International Federation of Organic Agriculture Movements, but around 100 different sets of standards exist worldwide. The market for organic produce is expanding and the value of this demand totaled $27.8 billion in 2004. Since organic produce sells for higher prices than conventional equivalents, an economic incentive exists for intentionally mislabeling produce as organic, even if it does not meet the set standards. Synthetic fertilizers used by conventional farmers are banned by organic standards, replaced instead with crop rotations, green manures and legumes, and substances that boost soil nutrients such as animal manures, fishmeal, and seaweed-derived products. The new test developed by Kelly’s team is based on mass spectrometry, and checks for the nitrogen isotope ratio in the food. Nitrogen isotope analysis was conducted on freeze-dried samples of both conventionally grown and organically grown produce and the resulting nitrogen isotope data reported in standard d notation in units of per mil with respect to atmospheric nitrogen (air) according to the equation d15Nsample (‰) = [(Rsample 2 Rstandard)/Rstandard] 3 1000 ‰ where R = 15N/14N and the standard is atmospheric nitrogen. Synthetic fertilizers have nitrogen isotope ratios (d) close to zero, usually between 22 and 2‰ since their nitrogen content is derived from unfractionated air. For organic manure-based fertilizers, the nitrogen ratio is 10–20‰. Researchers found differences in the nitrogen isotope composition of tomatoes, lettuces, and carrots grown organically and conventionally—an indication of whether the crop was grown with synthetic nitrogen fertilizer (Figure 2). Researchers indicate that such a test could be important in providing evidence on authenticity, helping to protect both consumers and honest organic growers. However, they emphasize that the test is not unequivocal, but may be used to

Figure 2. Histograms showing the d15N‰(air) values of organic and conventional crops (a) tomatoes, (b) lettuces, (c) carrots. Reprinted with permission from J. Agric. Food Chem. 2007, 55, 2664–2270. Copyright 2007 American Chemical Society.

1244 Journal of Chemical Education  •  Vol. 84  No. 8  August 2007  •  www.JCE.DivCHED.org

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Reports from Other Journals provide supplementary “intelligence” in an enforcement situation. Consequently, the authors also stress the importance of the existing organic certification and inspection programs. More Information 1. Bateman, Alison S.; Kelly, Simon D.; Woolfe, Mark. Nitrogen Isotope Composition of Organically and Conventionally Grown Crops. J. Agric. Food Chem. 2007, 55, 2664–2270. 2. This Journal has previously published a laboratory on the identification of pesticide residues in food. See J. Chem. Educ. 1973, 50, 855. 3. Online coverage of this research can be found at http://www. ifr.ac.uk/Science/ScienceBriefs/070413organictest.html, http://www. sciam.com/article.cfm?articleID=F1856AA5-E7F2-99DF-3D96F7F C7243D857&chanID=sa003, and http://www.rsc.org/chemistryworld/ News/2007/April/13040701.asp (all sites accessed May 2007).

An Ancient Inca Tax and ­Metallurgy in Peru Metal pollution is nothing new. Pre-industrial contamination in North America as old as 3,000 years has been identified from the study of ice cores, peat cores, and lake sediments. Investigations into the metal pollution generated by coinage and smelting in South America have previously been less extensive. But now scientists in the United States and Canada are reporting the first scientific evidence that ancient civilizations in the Central Andes Mountains of Peru smelted metals, and hints that a tax imposed on local people by ancient Inca rulers forced a switch from production of copper to silver. The University of Alberta’s Colin A. Cooke and colleagues point out that past evidence for metal smelting, which involves heating ore to extract pure metal, was limited mainly to the existence of metal artifacts dating to about 1,000 C.E. and the Wari Empire that preceded the Inca. The new evidence emerged from a study of metallurgical air pollutants released from ancient furnaces during the smelting process and deposited in lake sediments in the area. The study was based at the Morococha mining region of central Peru and Laguna Pirhuacocha, a small lake 11 km northeast of Morococha with no hydrological connection to any mining activity (Figure 3). The scientists measured levels of copper, lead, zinc, antimony, bismuth, and silver, all of which are associated with local

ores, and titanium, which comes from local crustal rocks (see table below). The levels of lead formed the basis of scientific interpretation. Since it is not affected by post-depositional mobility in lake sediment, stable Pb isotope ratios can trace the source of ore, and the mineral galena (PbS) was used by Inca as a flux in smelting. Cooke’s team was able to calculate sediment ages for the last 130 years using the short-lived radioisotope 210Pb in the constant initial concentration (CIC) dating model, while 14C dating was used to estimate dating beyond the range of 210Pb. Metals in each sediment sample were measured using inductively coupled plasma–atomic emission spectroscopy (ICP–AES) or ICP–mass spectrometry (ICP–MS), and lead isotopic ratios were measured with ICP–MS. By looking at changes in the amount of pollutant metals present in each sample, the researchers recreated a 1,000-year history of air pollution due to metal smelting in the area, predating Francisco Pizarro and his Spanish conquistadors by 600 years. Their findings show that smelters in the Morococha region of Peru switched from production of copper to silver around the time that Inca rulers imposed a tax, payable in silver, on local populations. More Information 1. Cooke, Colin A.; Abbott, Mark B.; Wolfe, Alexander P.; Kittleson, John L. A Millennium of Metallurgy Recorded by Lake Sediments from Morococha, Peruvian Andes. Environ. Sci. & Technol. 2007, 41, 3469–3474. 2. This Journal has published numerous articles on metallurgy. See J. Chem. Educ. 1995, 72, 416 and J. Chem. Educ. 1987, 64, 526. 3. Wolfe’s Web page, available at http://faculty.eas.ualberta. ca/wolfe/ (accessed May 2007), features additional discussion and references. 4. Additional discussion of this work is available online at http:// sciencenow.sciencemag.org/cgi/content/full/2007/420/1?rss=1 (accessed May 2007)

Angela G. King is Senior Lecturer in Chemistry at Wake Forest University, P.O. Box 7486, Winston-Salem, NC 27109; [email protected].

Peak and Background Concentrations (mg/g), Enrichment Factors (Peak to Background Ratios), and the CIC Age of Peak Metal Concentration within Laguna Pirhuacocha Sediment Zn

Peak concentration (mg g21) Background concentration (mg

g21)

Enrichment Factor (peak/background ratio) CIC age of peak enrichment

Ti

Pb

Cu

Ag

Sb

Bi

2512

170

1.52

14

72

835

56

45

46

14

26

0.02

0.02

0.02

19

1

185

7

75

600

3863

2005

1957

1974

1974

2005

2005

1974

Reprinted with permission from Environ. Sci. & Technol. 2007, 41, 3469–3474. Copyright 2007 American Chemical Society.

1246 Journal of Chemical Education  •  Vol. 84  No. 8  August 2007  •  www.JCE.DivCHED.org

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Figure 3. (a) Map of Peru showing study area and sites mentioned; (b) magnification of the central Andean region; (c) base map of the Morococha mining region, Laguna Pirhuacocha, and the nearby Puypuy glacier, which lies outside of the Laguna Pirhuacocha catchment. Image credits: Reprinted with permission from Environ. Sci. & Technol. 2007, 41, 3469–3474. Copyright 2007 American Chemical Society.



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