Reversing Diabetes Type 2 and Prediabetes

An open Letter to President Obama:
 
Research presented at the Radiological Society of America’s November 2011 meeting showed that a cohort of obese men and women with type 2 diabetes mellitus was able to reverse the symptoms of their disease by following a calorie-restricted diet. In fact, they were able to eliminate their need for insulin medications.
After following a low, 500 calorie a day, diet for four months -- the average body mass index of the obese cohort dropped significantly from 35.3 to 27.5, while indicators of their cardiovascular function improved.*
As leaders of calorie restriction and practice, we recommend that anyone with type 2 diabetes or prediabetes who wants to follow a  low calorie diet intervention like that used in the study, do so under medical supervision. Normally, a person who follows a calorie-restricted diet eats three or four times more calories than the amount used.
We do recommend that physicians consider using calorie restriction lifestyle and diet plans as a treatment plan for type 2 diabetes diabetes and prediabetes.
The Centers for Disease Control estimates that diabetes affects 25.8 million people in the U.S., or roughly 8 percent of the population. The vast majority of cases are type 2 diabetes, the type associated with obesity.  Seventy-nine million more are estimated to have prediabetes.  This is more than one-third of all  Americans.
Please help us reverse this personal tragedy that ruins the lives of so many and that places an intolerable burden on the nation’s healthcare system. We need to make physicians aware that safe, healthful, and manageable calorie restriction lifestyle plans are available for those who want to reduce the severity of type 2 diabetes, and for anyone to have the best chance to avoid disease and enjoy a healthy, happy, long, and productive life.
 
*Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function.
J Am Coll Cardiol. 2008 Sep 16;52(12):1006-12.
PMID:18786482, from NIH, NLM, PubMed access to Medline's bibliographic citations
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For more see:
The CR Way to Great Glucose Control

 The CR Way Diabetes Intervention Membership

 Diabetes and Glucose Control Forum

Diabetes

Calorie Restriction: Reversing age-related decline in 6 months!

Maybe we’re all having Midsummer Night’s Dreams, but we’d like to bring a reality to your attention. We probably don’t have to tell you that eyesight deteriorates with age. What you may not know is that this is not a necessary forecast. Take a look —

Which of the following lines can you read?

If you can read all of them at 100% normal size – reduce the viewing size to 75%, then 50%, etc., until line 4 is no longer legible.

This is a most important day. It is the day when I start to grow younger.
This is a most important day. It is the day when I begin to achieve my goals.

This is a most important day. Today I grow healthier & happier – more able to do what I want to do.

This is a most important day. It is the beginning of the reversal of my age-related decline

The CR Way helps you make extraordinary health gains by putting science into practice. Improving eyesight is one of them. After six months of following the CR Way, you will almost certainly be able to see better.

If you aren’t yet travelling the CR Way™ – start today. And set the goal of being able to read one print size smaller than you can today six months from now.

Other life-changing benefits you are likely to appreciate:

• Weight loss, if you need it
• Lower disease risk: cancer, diabetes, and Alzheimer's, heart, and kidney disease
• More energy
• Better thinking power
• Less inflammation
• Better outlook – more positive and optimistic
• Increased chances for longer life.

Here’s a second challenge to give you the opportunity for another success:

Take your picture now and again in six months to see your physical improvement for yourself. Then, if you would like to inspire others,  share them with the CR Way™ community on the CR Way Longevity Center on Facebook.

Calorie Restriction: Glucose Control is Vital!

Those who follow the CR Way know that blood glucose control is emphasized (see The CR Way, Chapter 4, for example: “Glucose Control: The Sweet Spot in Longevity”). While many search for a drug to mimic the effects of CR or to increase CR’s age-slowing effect, turn around, Dorothy, and click your heels three times because a natural way to increase CR benefits has been readily available for years – Keeping Glucose Low!

The benefits of low glucose are so profound that they are documented throughout LivingtheCRWay.com and include –


More energy
Increased protection from cancer
Increased cognitive ability
Better eyesight
Increased protection from heart disease
More protection from diabetes
Increased expression of longevity genes

Meanwhile, glucose control is also important in reducing formation of AGEs (Advanced Glycation Endproducts) — a potential side effect of long-term CR when practiced without the CR Way approach of gently teasing insulin into production. In a groundbreaking study, CR research greats – Luigi Fontana, Samuel Klein, and John O. Holloszy – found that 40% of those practicing long-term calorie restriction were not producing enough insulin to easily dispose of the bolus of glucose, which is poured down the throat of unfortunate individuals who undergo a standard glucose tolerance test. [Oral Glucose Tolerance Test (OGTT) includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg). It is supposed to be a test to determine the ability of an individual to maintain homeostasis of blood glucose. However, when people who intentionally ingest very little sugar and other food that is digested quickly to glucose and therefore secrete very little insulin – only what is required for their small sugar intake – are given this test, the glucose floods their systems, leading to the opposite of homeostasis and providing no useful data.] Fructosamine, a marker of AGE formation, was higher in this group.

Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action,
and adipokine production.
Luigi Fontana, Samuel Klein, John O. Holloszy
Age (Dordr). 2010 Mar;32(1):97-108. Epub 2009 Nov 11.

Abstract
Calorie restriction (CR) slows aging and is thought to improve insulin sensitivity in laboratory animals. In contrast, decreased insulin signaling and/or mild insulin resistance paradoxically extends maximal lifespan in various genetic animal models of longevity.

Nothing is known regarding the long-term effects of CR on glucose tolerance and insulin action in lean healthy humans. In this study we evaluated body composition, glucose, and insulin responses to an oral glucose tolerance test and serum adipokines levels in 28 volunteers, who had been eating a CR diet for an average of 6.9±5.5 years, (mean age 53.0±11 years), in 28 age-, sex-, and body fat-matched endurance runners (EX), and 28 age- and sex-matched sedentary controls eating Western diets (WD).

We found that the CR and EX volunteers were significantly leaner than the WD volunteers. Insulin sensitivity, determined according to the HOMA-IR and the Matsuda and DeFronzo insulin sensitivity indexes, was significantly higher in the CR and EX groups than in the WD group (P=0.001). Nonetheless, despite high serum adiponectin and low inflammation, approximately 40% of CR individuals exhibited an exaggerated hyperglycemic response to a glucose load.

This impaired glucose tolerance is associated with lower circulating levels of IGF-1, total testosterone, and triiodothyronine, which are typical adaptations to life-extending CR in rodents.

PMID: 19904628

From the full-text of the paper:

"Aging and many age-associated diseases in both humans and rodents are associated with progressive increase in fasting insulin concentration and insulin resistance (Meigs et al. 2003; Basu et al. 2003; Reaven 1995). However, the relationship between aging/aging related diseases and insulin resistance is confounded by associated factors such as excessive abdominal adiposity, decreased physical activity, hyperinsulinemia, dyslipidemia, inflammation, and other metabolic and hormonal components of the metabolic syndrome (Barzilai et al. 1998; Reaven 1995).

It is intriguing that based on the 2-h OGTT plasma glucose values, 11 of our CR subjects met diagnostic criteria for glucose intolerance (Genuth et al. 2003), and six of the CRNGT (CR Normal Glucose Tolerance) subjects had high–normal 2-h glucose values, even though all CR subjects were extremely lean and had very low fasting plasma concentrations of glucose and insulin, and an outstanding metabolic profile (very low triglyceride, high HDL-cholesterol, high adiponectin, and extremely low C-reactive protein concentrations; Fontana et al, 2006).”

All of these markers are associated with increased longevity and protection from disease. In fact, the study shows that those who were not able to dispose of the glucose influx easily (CR-IGT -- (CR Impaired Glucose Tolerance) had better scores on key markers – testosterone, adiponectin, IGF-I – than the CR group that did well in the glucose tolerance test (CR-EGT). It is likely that the CR-EGT group consumed a high protein diet, which would explain the extraordinarily high IGF-I scores at the high end of the reference range. For more see "Excess Protein Negates key Longevity Marker," a blog post that can be accessed for free by becoming a Healthy Start member of LivingtheCRWay.com

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Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production

Luigi Fontana, Samuel Klein, John O. Holloszy - ©American Aging Association 2009

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Some speculate that the long-term CR group had “insulin resistance,” a condition in which the body produces insulin, but doesn’t use it properly. The paper states:

"decreased insulin sensitivity and glucose disposal could enhance survival, by preventing hypoglycemia and maintaining circulating glucose for organs that require glucose as a fuel."

We think that rather than decreased insulin sensitivity, we are simply seeing decreased insulin production, a goal of long-term calorie restriction – as increased insulin production is associated with decreased longevity and increased cancer, diabetes, and both heart and Alzheimer’s diseases.

In fact, a standard oral glucose test is probably not appropriate to judge insulin secretion in a normal healthy calorie restrictor. Looking at the activity level of glucagon, the glucose-maintaining hormone, produced by pancreatic a cells when calorie intake is low would be more informative.

Prevention of AGE formation

While decreased insulin production is likely to be vital for CR benefits, having little insulin around to dispose of glucose could result in increased formation of AGEs (Advanced Glycation Endproducts) – biological garbage that has many deleterious effects. Because of this, The CR Way recommends the tease meal to start the huge metabolic shift from fasting, e.g.: overnight, to food intake -- from more inactive growth operations that are powered by insulin to insulin production, allowing the body to deal effectively with circulating glucose.

For tease meal suggestions see --

Paul McGlothin & Meredith Averill. The CR Way, NY: HarperCollins, 2008, pp. 191-194
The CR Way to Happy Dieting, available to Longevity Level members of LivingTheCRWay.com
"Lentil Tomato Tease" Recipe in the NutriBase CR Way Edition Software. Note that the software makes it easy to plan tease meals, which have a separate section in the food log and a tracking section for charting of glucose effects.
To get a head start on glucose control, find out more about The CR Way Glucose Control Kit

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Barzilai N, Banerjee S, Hawkins M, Chen W, Rossetti L
Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat.
The Journal of Clinical Investigation. 1998 Apr 1;101(7):1353-61.
PMID: 9525977

Basu R, Breda E, Oberg AL, Powell CC, Dalla Man C, Basu A, Vittone JL, Klee GG, Arora P, Jensen MD, Toffolo G, Cobelli C, Rizza RA
Mechanisms of the age-associated deterioration n glucose tolerance: contribution of alterations in insulin secretion, action, and clearance.
Diabetes. 2003 Jul;52(7):1738-48.
PMID: 12829641

Meigs JB, Muller DC, Nathan DM, Blake DR, Andres R, Baltimore Longitudinal Study of Aging
The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging.
Diabetes. 2003 Jun;52(6):1475-84.
PMID: 12765960

Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, Kitzmiller J, Knowler WC, Lebovitz H, Lernmark A, Nathan D, Palmer J, Rizza R, Saudek C, Shaw J, Steffes M, Stern M, Tuomilehto J, Zimmet P; Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
Follow-up report on the diagnosis of diabetes mellitus.
Diabetes Care. 2003 Nov;26(11):3160-7.
PMID: 14578255

Reaven GM
Pathophysiology of insulin resistance in human disease.
Physiological Reviews. 1995 Jul;75(3):473-86. Review.
PMID: 7624391

When Calorie Restriction Isn’t Calorie Restriction!

Some people say that a calorie restriction diet is difficult to follow. It used to be. But things have changed: Thanks to great work by leading scientists, calorie restriction is just as much about cell signaling as it is about limiting calories.

It is known, for example, that serious long-term calorie restriction dramatically lowers insulin levels, which is vital for longevity. Another hormone, with a very similar molecular structure, insulin-like growth factor one (IGF-I), shares the same pathway with insulin and is downregulated by calorie restriction as well.

The bad news is that if you do not pay attention to the special properties of individual foods, they can -- independent of calories -- stimulate the insulin/IGF-I pathway. At that point, CR should not stand for Calorie Restriction but rather Cancer Risk, since it is known that high levels of either hormone increase the likelihood of contracting cancer, as well as the risk of getting many chronic diseases -- including diabetes and both heart and Alzheimer’s disease.

Back in the 1930s when the term calorie restriction was first applied to some rat and mice experiments, it was entirely appropriate because the focus was on calories since little was known about the signals involved in the life-extending effects of the diet. All that changed as scientists discovered important cell signaling patterns that produced the phenomenal life-transforming effects.

In 2008, The CR Way took the cell-signaling patterns that were known and integrated them with strategies to create a holistic lifestyle. This makes it much easier to follow a CR diet because it's turned into a happy, positive lifestyle that focuses on living better now and quite possibly longer. Delicious recipes and food choices are offered that help lower the insulin/IGF-I pathway – reducing disease risk, while making it easier to lose weight if you need to.

Music Principles Improve Brain Power

A well trained professional classical musician can immediately identify a performance by an amateur. Too often, amateurs try to perform a piece before they are ready. Consider, for example, this very difficult Chopin Scherzo performed here by one of the greatest pianists of all time, Vladimir Horowitz:

 Time and again, amateurs will practice such a piece at top speed. Here is the results of such an approach can sound like. It is hard to tell that it is the same piece:

A professional will practice a piece like this in slow motion – listening to every note to make sure it is executed cleanly and evenly as required and integrate any other techniques that raise the level of performance to truly beautiful expression. Only when it is perfect in slow motion will they increase the tempo little by little until they can consistently perform a work flawlessly at top speed. Practicing in this way is how great musicians like Vladimir Horowitz perform at such a high level.

We use the same principles to train Brain Booster Members: First we go over all the basic CR Way “techniques” that must be in place to activate the biochemistry that facilitates neural plasticity (changing of the structure, function, and organization of neurons in response to new experiences). Then we add a large and growing number of complementary practices that increase the capacity for learning.

As people put these fundamentals in place (the equivalent of practicing scales, arpeggios, and other basics of classical music), we encourage practicing the brain-training game, Dual N-back – and, of course, this is what we do ourselves!

Some N-Back users suggest a benefit in training at higher N-Back levels – before they have mastered lower levels, hoping this will help them progress faster. I suggest that this is equivalent to the performance of an amateur musician. Approaching N-Back improvement methodically is far better: practicing N-Back in slow motion – not progressing until your score is perfect at lower levels. This, combined with CR biochemistry, is the way to truly improve N-Back skill and ultimately your brain power.

Stand for Longer Life!

We have often written about various lifestyle practices that could negate CR benefits. One of them is sitting for long periods of time. Think about it: How much time do you spend sitting each day? The more time you sit, the more you risk death from all causes:

Sitting time and mortality from all causes, cardiovascular disease, and cancer.
Medicine and Science in Sports and Exercise. 2009 May;41(5):998-1005.
Katzmarzyk PT, Church TS, Craig CL, Bouchard C.
Pennington Biomedical Research Center, Baton Rouge, LA 70808-4124, USA. Peter.Katzmarzyk@pbrc.edu

Purpose: 

…We prospectively examined sitting time and mortality in a representative sample of 17,013 Canadians 18 to 90 years of age. 

Methods:

Evaluation of daily sitting time (almost none of the time, one fourth of the time, half of the time, three fourths of the time, almost all of the time), leisure time physical activity, smoking status, and alcohol consumption was conducted at baseline. Participants were followed prospectively for an average of 12.0 years for the ascertainment of mortality status. 

Results:

There were 1832 deaths (759 of cardiovascular disease (CVD) and 547 of cancer) during 204,732 person-years of follow-up. After adjustment for potential confounders, there was a progressively higher risk of mortality across higher levels of sitting time from all causes…and CVD…but not cancer. Similar results were obtained when stratified by sex, age, smoking status, and body mass index...

Conclusions:

These data demonstrate a dose-response association between sitting time and mortality from all causes and CVD, independent of leisure time physical activity. In addition to the promotion of moderate-to-vigorous physical activity and a healthy weight, physicians should discourage sitting for extended periods.

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PMID:19346988, lightly edited from National Institutes of Health, National Library of Medicine, PubMed. PubMed.gov. accessed, May 15, 2011

Some who are reading this may think that exercise can counter the bad effects of their daily sitting habits. This is probably not the case. In an interview, the principal investigator of the study, Peter Katzmarzyk, was quoted as saying that sitting is an independent risk factor for death – No matter what your lifestyle: smoker or not , exerciser or not.*

*Men’s Health. Bill Phillips and the editors: “The Most Dangerous Thing You'll Do All Day.”
 Mar 30, 2011

One of the reasons that sitting causes such problems is that it raises glucose levels – countering a basic tenant of CR Way practice. And we know that higher glucose levels increase risk for cancer, diabetes and heart disease while likely making longevity genes quiescent.

Moreover – simple, passive standing facilitates digestion and bowel motility, contributes to osteoporosis prevention, and increases concentration. So, just as a way to increase quality of life – standing makes sense.
Such knowledge made us change our lifestyle and spend a lot more time on our feet. To do this, several things had to change:

First, were our work stations. We had to have the flexibility to sit or stand while working at our computers and to be able to change the height of the standing position so that Meredith at 5’ 4” and Paul at 5’ 11’ could use them. Here, the goal was to have our computer monitor positioned so we are looking straight at the screen.

We also wanted something that was affordable, yet good looking. Besides our esthetic preferences, if the media folk who come here wanted to do an interview with us at a workstation, we would feel comfortable having it seen on television.

After quite a bit of looking, we decided on the Wallaby, a simple desktop that allows us to sit or stand, positions the monitor ergonomically, provides enough space for things like work materials and a glass of water, besides the mouse and keyboard. It is part of a family of products:  Sit or Stand Desktops for people who want to avoid the life-shortening risks of sitting and get the life-enhancing benefits of standing.

Still, standing for long periods can increase foot problems, especially for slim people who might be at risk for plantar fasciitis, a painful foot condition that can include swelling. So we use a thick rubber yoga mat to stand on so that the floor in front of our computers is softer.

We also use MBT Shoes, which are well known for providing many health benefits and thick, foot-protecting socks to make it much easier to stand for long periods of time much easier.

The yoga mat, shoes, and socks are also part of our strategy for minimizing irritation, for example when we do jumping exercises – part of the CR Way practice for building strong bones.


And moving about makes sense too. We don’t advocate standing rigidly for hours. So we   take occasional exercise breaks to keep us on our feet for most of the day and moving around as much as possible. This helps glucose stay low, helping burn fat that might otherwise end up in arteries.

"You are What you Don't Eat!"

The CR Way

4/1/2011 2:18:16 PM

We had the good fortune to participate in a terrific press conference, hosted by the American Federation of Aging Research (AFAR). AFAR is a forward-looking organization that provides financial support for early- and mid-career scientists who are developing careers in the study of aging. This conference, entitled “You are What you Don’t Eat!” presented two world-famous CR scientists, Drs. Luigi Fontana and Donald Ingram. After an introduction from AFAR's board member, Dr. Jack Watters, both scientists shared many profound insights that could extend healthy lifespan for millions of people. 

Dr. Fontana first reminded us how important calorie restriction research is for the health and financial viability of the health care system: “Cardiovascular disease (CVD), cancer, stroke and diabetes account for nearly 70% of the deaths in the United States and Europe. About 80% of adults over 65 years of age have at least one chronic disease, and 50% have two or more of these chronic diseases that accelerate the aging process¹ .” The point he makes is that health care systems, especially with our rapidly aging population cannot sustain this large number of people with disease. 

Meanwhile, his CR studies – many done in conjunction with the CR Society Intl. – show that those following a serious CR diet exhibit less risk of CVD, cancer, stroke, and diabetes – all chronic diseases that people in Western societies are so prone to. Drawing parallels with animal studies, Fontana points out that CR mice are found to live much longer and in better health. When they die, autopsies show no sign of a chronic condition. Dr. Fontana says the same is possible for people. He hailed the healthiest old people as “escapers:” people who live to 100 and contract no chronic disease. 

Against that backdrop, Dr. Fontana explained that his human CR studies have looked carefully at various markers in human calorie restrictors – T3, IGF-I, insulin, glucose, correlating them to successful CR, established in animal studies. This has given him a battery of indicators that can used by anyone to judge the effectiveness of a CR regimen. These are the core of the CR Way biomarkers that we recommend for testing and tracking by anyone following a CR diet. Fontana’s presentation underlines the reality that living free of chronic disease is attainable for humans.

Dr. Ingram presented valuable research results.  He discussed many aspects of  his productive CR research career, including his search for a CR mimetic. He has looked at some well known candidates such at Metformin (producing no difference in life span extension in his studies), 2 d-oxyglucose, (proving to be unusable because of dangerous side effects in the heart). And a promising possibility: avocado-derived mannoheptulose. Highly recommended by The CR Way, avocados have a profound glucose/insulin-lowering effect, according to Dr. Ingram. He attributes this to mannoheptulose, a sugar that’s rare in the human diet and that reduces glycolysis via hexokinase inhibition.

Bioavailability of avocado-derived mannoheptulose in dogs

Gary Davenport¹, Stefan Massimino¹, Michael Hayek¹, Michael Ceddia¹, John Burr¹, Chyon-Hwa Yeh¹, Lijuan Li¹, George Roth² and Donald Ingram³

¹ Procter & Gamble, Lewisburg, OH
² Geroscience, Pylesville, MD
³ Pennington Biomedical Research Center, Baton Rouge, LA

The FASEB Journal: The Journal of the Federation of the Societies for Experimental Biology, now on their Web site: http://www.fasebj.org/cgi/content/meeting_abstract/24/1_MeetingAbstracts/725.3, accessed April 1, 2011 

Mannoheptulose (MH) is a 7-carbon sugar found in avocados and other natural sources that acts to reduce glycolysis via hexokinase inhibition. It has been proposed as a calorie restriction (CR) mimetic that delivers anti-aging and health-promoting benefits of CR without reducing food intake. Three studies were conducted to evaluate MH bioavailability when fed to dogs as an avocado extract (AvX) based on MH levels in urine (Study 1) and plasma (Study 2 & 3). In Study 1, Labrador Retrievers (LR; n=15) and Fox Terriers (n=15) were fed AvX-containing diets formulated to deliver 0, 2 or 5 mg MH/kg BW. All dogs were subjected to 24-hour quantitative urine collections. A dose-dependent increase (p<0.05) in urinary MH occurred with increasing dietary MH. In Study 2, LR (n=6) were fed AvX-containing diets once daily to deliver 0, 1 or 2 mg MH/kg BW. Sequential blood samples were collected before and after feeding through 12 hr and at 24-hr post-feeding. Plasma MH increased (P<0.05) with both MH diets compared to control. Peak MH occurred 6–8 hr post-feeding and returned to non-detectable levels by 24 hr. In Study 3, similar MH results were observed for LR (n=10) fed AvX-containing diets twice daily to provide 0 or 2 mg MH/kg BW. Peak MH occurred within 2–4 hr of MH consumption and returned to non-detectable levels by 24 hr.

Mannoheptulose, fed as an avocado extract, is biologically available in dogs based on its appearance in plasma and urine.

Dr. Ingram shared some additional successful research² on the neuroprotective effects of blueberries. He and his colleagues found that mice that were injected with a blueberry extract were protected against neurodegeneration induced by a toxic substance.

The growing interest in phytonutrients for health and longevity was reinforced by Dr. Fontana, who reported a current experiment gauging the effects of a cocktail of polyphenol extracts.

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On behalf of everyone interested in longevity, we asked the scientists to tell us where they think the next important areas of their research should be. Dr. Fontana wants to turn his attention to CR and cancer, noting that many unknowns continue to make preventing cancer’s occurrence – even predicting its likelihood – difficult. He reminded us that “cancer is the second leading cause of death in many developed countries," accounting for approximately one-fourth of all deaths. Among women, aged 40 to 79, and among men aged, 60 to 79, cancer is the leading cause of death in the U.S. The lifetime probability of developing cancer is 46% for men and 38% for women²  .  Furthermore, many of the processes of cancer mirror processes of aging, so this research will do double duty.

Dr. Fontana believes that by looking at CR, which has been shown to reduce cancer incidence and rate of metastasis in animal and human studies³, better ways will be found to predict the likelihood of cancer as well as to prevent it.

This line of study will also help determine potential aging markers, a recurring theme for both presenters. Dr. Ingram declared in his answer to our question: Rate-of- aging markers need to be established and validated. Future projects need to focus on this work. Further, he called on the gerontological community to work hard on building consensus on these biomarkers, so that they can be used by researchers, healthcare professionals, and longevists.

We are heartened to know that forward-thinking organizations like AFAR are facilitating the work of talented scientists who will likely make it possible ultimately for all to live in good health longer.

The hope of the CR Society Intl. and the CR Way is that the work of these scientists will be fully appreciated and that government and other funders will respond with the support that is needed to pursue research that helps us all live longer, disease-free lives and ultimately makes a big difference in the financial viability of health care.

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 ¹ Modulating Human Aging and Age-Associated Diseases

Luigi Fontana, M.D., Ph.D.

Biochimica Biophysica Acta. 2009 Oct;1790(10):1133-8. Epub 2009 Feb 10.

Population aging is progressing rapidly in many industrialized countries. The United States population aged 65 and over is expected to double in size within the next 25 years. In sedentary people eating Western diets aging is associated with the development of serious chronic diseases, including type 2 diabetes mellitus, cancer and cardiovascular diseases. About 80 percent of adults over 65 years of age have at least one chronic disease, and 50 percent have at least two chronic diseases. These chronic diseases are the most important cause of illness and mortality burden, and they have become the leading driver of health care costs, constituting an important burden for our society.

Data from epidemiological studies and clinical trials indicate that many age-associated chronic diseases can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. Several recent studies suggest that more drastic interventions (i.e. calorie restriction without malnutrition and moderate protein restriction with adequate nutrition) may have additional beneficial effects on several metabolic and hormonal factors that are implicated in the biology of aging itself. Additional studies are needed to understand the complex interactions of factors that regulate aging and age-associated chronic disease.

PMID: 19364477

  ²A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats.

Duffy KB, Spangler EL, Devan BD, Guo Z, Bowker JL, Janas AM, Hagepanos A, Minor RK, DeCabo R, Mouton PR, Shukitt-Hale B, Joseph JA, Ingram DK.

Laboratory of Experimental Gerontology, Intramural Research Program, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.

Neurobiology of Aging. 2008 Nov;29(11):1680-9. Epub 2007 May 23.

Young male Fischer-344 rats were fed a diet containing 2% blueberry (BB) extract or control diet for at least 8 weeks and then received bilateral hippocampal injections of kainic acid (KA 200 ng/0.5 microl) or phosphate buffered saline (PBS). One week later rats were trained in one-way active footshock avoidance in a straight runway followed the next day by training in a footshock motivated 14-unit T-maze with documented sensitivity to hippocampal glutamatergic manipulations. Based on analyses of several performance variables, KA-treated rats exhibited clearly impaired learning performance; however, the BB diet significantly reduced this impairment. Supporting the behavioral findings, stereological assessment of CA1 pyramidal neurons documented greater neuronal loss in KA-treated controls compared to KA-treated rats on the BB diet.

In an in vitro experiment, FaO cells grown in medium supplemented with serum from BB-fed rats had enhanced viability after exposure to hydrogen peroxide. These findings suggest that BB supplementation may protect against neurodegeneration and cognitive impairment mediated by excitotoxicity and oxidative stress.

³ Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research.
Hursting SD, Smith SM, Lashinger LM, Harvey AE, Perkins SN.
Carcinogenesis. 2010 Jan;31(1):83-9. Epub 2009 Dec 7.

Calorie restriction (CR) is arguably the most potent, broadly acting dietary regimen for suppressing the carcinogenesis process, and many of the key studies in this field have been published in Carcinogenesis. Translation of the knowledge gained from CR research in animal models to cancer prevention strategies in humans is urgently needed given the worldwide obesity epidemic and the established link between obesity and increased risk of many cancers.

PMID: 19969554

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