Control of Human Aging With Special Nutritional Program.
Presentation of the Method
By Arcady L. Economo. Ph.D, Pharm.D. Anti-Aging Center Europe

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Key words: aging, dietary restriction, nutritional program, human life span extension
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ABSTRACT
Dietary restriction proved to be extremely effective for extending maximum life span in animals. Are the animal data translatable to humans? Modern scientific data indicates that with high order of probability we can answer on this question yes ! If yes than we ought to change our diet. The purpose of this work was to develop special nutrient criteria for human being - Anti-Aging Dietary Norms (AADN) for construction of various anti-aging food regimes - that are low-calorie, properly balanced and individually adjusted. 42 Versions of AADN were developed on the basis of present scientific data on biology of aging process: 7 versions for Standard model, 9 versions for Diabetic model, 17 versions for Gastroentheropathy model and 9 versions for Ischemic heart disease & Hypertension model. Using AADN-tables and originally developed computer program we can maintain within optimal ranges the intake with diet of 58 essential nutrients. Such a nutritional supervision on human being and the condition of caloric limitation will lead to an essential reduction of the rate of human aging. Panel of Experts - International Anti-Aging Expert Commission certified five values for each of 58 essential nutrients: A - minimum required, B - low optimum, I - ideal value, C - high optimum, D - unsafe level.

INTRODUCTION
Since the 1930s, caloric limitation of diet, y.e. dietary restriction(DR) has been the only intervention shown to slow aging in warm-blooded organisms. Early DR experiments of Clive M. McCay(1), who placed rats on a very low calorie diet and extended animal’s life span by 40 percent had been nowadays repeated in numerous experiments on mice and rats - for review see a comprehensive monograph of R. Weindruch and R.L. Walford(2). Mechanisms by which DR extend life span in rodents is now become more clear(3). DR decreases susceptibility to most diseases and significantly reduces aging rate in animals(4). There are ongoing trials of DR’s influence on aging in non-human primates(5,6). Preliminary observations furnished no proof that the quality of life of DR monkeys is impaired in any way. For human beings numerous low-calorie diets were introduced as an anti obese and therapeutic method. Low-calorie diets significantly improve various bio-markers of human aging(2,7,8,9). Even the American Dietetic Association, known for their conservatism, agreed with beneficial health role of low-calorie regimes for human beings(10).

Modern scientific data indicates that DR will with a high order of probability retard the rate of aging and extend life span in humans(2,7). Yet to achieve anti-aging goal low-calorie diets should be properly balanced in terms of all essential nutrients. Some of these nutrients - Vitamin E, Vitamin C, beta-Carotene, Selenium and others have intimate link with the aging process. Till now specialists on aging, dietitians and nutritionists have no unanimity of views upon: first - what nutrients are essential for anti-aging diet regimes, second - how much of these nutrients should be entered our organism daily with meals. In present work we tried to answer the questions what nutrients? and how much? As a result an anti-aging nutritional criteria - ANTI-AGING DIETARY NORMS(AADN) were developed. AADN have to serve as a standard guide for everybody, who want to control aging by nutritional methods.

MATERIAL AND METHODS

Definition
ANTI-AGING DIETARY NORMS are defined as the levels of intake of essential nutrients that the International Anti-Aging Expert Commission on the basis of scientific knowledge on biology of aging process, judges to be adequate and optimum for the maximum prevention of human aging process. The AADN are amounts intended to be consumed as part of a normal varied diet. AADN were developed for healthy persons (Standard version of AADN-tables) and for individuals with special health problems (Disease version of AADN-tables).

Philosophy
AADN-tables are intended to be a scientific and practical basis for gerontologists, nutritionists, dietetic practitioners and practical physicians, who deal with food planning as an anti-aging tool. Using AADN-tables one can prepare food rations in order to suppress human aging, diseases and obesity. AADN tables are in good correspondence with “US 10 Th. edition of the Recommended Dietary Allowances”, officially issued in 1989 by the Food and Nutrition Board of US National Academy of Sciences (1989 RDAs)(11). AADNs includes all 29 nutrients, that are presented in 1989 RDAs, but also contains other 29 essential nutrients. AADN are more complicated and diversified than 1989 RDAs. AADN are disease oriented tables. Certain types of health problems are correspondent to certain version of AADN-tables, that is in good correspondence with the recommendations of National Research Council(12) and of Americans Dietetic Association(10). AADN-tables are also in good agreement with the official recommendations of “The Surgeon General Report on Nutrition and Health”, that was published in 1989 by US Government(13).

Age/sex grouping
Although beneficiary effects of Anti-Aging food rations seems be achieved in any age group we consider that AADN-tables are developed for age groups starting from 20 years of age. We make no difference by sex in AADN-tables.

Design of AADN-tables
Generally every nutrient in AADNs tables is presented by five values: A- value (minimum required), B-value (low optimum), I-value (ideal value), C-value (high optimum), D-values (unsafe level). These values may differ for persons having different diseases or being on different caloric limitation regimes.

A-values (left column in AADN-tables) must be achieved while preparing daily meal plans. A values are to coincide with the corresponding male values of 1989 RDAs tables of age group 25-50 except Energy value. For those nutrients, that are not presented in 1989 RDAs A-, B-, I-, C- and D-values were developed by International Anti-Aging Expert Commission.

D-values (right column in AADN-tables) are corresponding to potentially undesirable level of nutrient intake or even to toxic values.

B- and C-values(two middle columns in AADN-tables) contains values of nutrients that indicate anti-aging optimum range for human beings. We consider that the rate of human aging for persons being on diet, when nutrients are within this optimum range (between B and C) is decreased to a minimum.

I-values (central column in AADN-tables) contains nutrient values, that are corresponding to the most desirable nutrient value. I-value’s position is between B- and C-values and its meaning is rather relative but serves as a basic figure for calculating of A-, B-, C- and D-values for some nutrients. AADN presents 5 values (A, B, I, C and D) for each of 58 essential nutrients that are combined into 6 subgroups: Main, Amino acids, Lipids, Carbohydrates, Vitamins and Elements. Methods of calculating of A-, B-, I-, C-, D-values for Standard model of AADN are presented below.

Main (include 8 nutrients)
Energy(E) (in kCal). Adequately adjusted daily energy intake has a crucial meaning for developing of anti-aging diet regimens. Although individual daily energy intake can be different depending on personal prescriptions, we used in present work 2000 kCal daily energy intake as a Standard value for all further calculations. A- and B-values are lower than the I-value by 6% and 3% correspondingly. C- and D-values are higher than I-value by 3% and 6% correspondingly. Thus for 2000 kCal regimes A-, B-, I-, C- and D-values should be 1880, 1940, 2000, 2060 and 2120 correspondingly (Table 1). AADN may have different versions depending on Energy content of a diet.

Proteins(Prot), Lipids(Lip), Carbohydrates(Carb) (as % of Energy). I-values for these nutrients are presented in Table 2 for different disease models. For Proteinsand Carbohydrates A- and B- values are lower than I-value by 30% and 20% correspondingly. C- and D-values are higher than I-value by 20% and 30% correspondingly. For Lipids A-, B-, C- and D-values are lower and higher than I-value by --60%, --50%, +20% and +50% correspondingly.

Indispensable Amino Acids (Total IAA) (as % of Energy). Total IAA’s daily intake is considered to be 33% of Total Protein Daily Intake(14). I-value for Total IAA is calculated by multiplying I-value for Proteins by 0,33. A-, B-, C- and D-values are lower and higher, than I-Total IAA value by --67%, --30% +50% and +100% correspondingly. A-value is correspondent to the recommendations of Food and Agriculture Organization FAO/WHO/UNU, 1985 (15).

Total fiber (in g) = Soluble fiber + cellulose + hemicellulose + lignin.

I-value for Total fiber is 25 g. A-, B-, C- and D-values are lower and higher than I-value by --30%, --20%, +20% and +40% correspondingly. Total fiber content should be decreased for persons with some gastrointestinal diseases, or for persons, who during long period of life were on low fiber food rations. (Gastroentheropathy version of AADN-tables).

Soluble fiber(FibS) (in g) = pectins + micilages + gums + algae&seaweeds + inulin.

I-value for Soluble fiber are calculated by multiplying of Total fiber’s I-value by 0,30. A-, B-, C- and D-values are lower and higher, than I-value by --30%, --20%, +20% and +40% correspondingly.

Water(H2O)(in g). I-value is 2000 g. A-, B-, C- and D-values are lower and higher than I-value by --25%, --15%, +15% and +25% correspondingly.

Amino acids (include 8 nutrients)
Amino acids include 8 nutrient parameters as % of Energy, that are corresponded to 10 Indispensable Amino Acids(IAA). We do not include Histidine in AADN-tables as well as indispensable statue of this amino-acid was proved only recently and requirements for this IAA is not yet established with certainty. However we took Histidine into account while calculating percentage ratio for certain IAA as we used the data from paper of P. Pellet, 1990 (16). If we consider 100% is total sum of IAA, than percentage ratio for certain amino-acid parameter(AA%) would be for Valine(Val) - 10,7%, for Isoleucine(Ile) - 10,7%, for Leucine(Leu) - 15,0%, for Lysine(Lys) - is 12,8%, for Methionine + Cystin(M+C) - 13,9%, for Threonine(Tre) - 7,5%, for Tryptophan(Trp) - 3,7%, for Phenylalanine + Tyrosine(P+T) - 15,0%, for Histidine - 10,7%. Ideal values for each of 8 IAA nutrient parameters are presented in AADN-tables as % of Energy (Table 1) and can be calculated by the following formula:

AA%E = Prot%E x 0.33 x AA% x 0.01 where

AA%E - I-value for certain AA parameter as % of Energy.

Prot%E - I-value for Protein as % of Energy.

AA% - percentage ratio for certain AA.

A-, B-, C- and D-values for certain AA parameter are lower and higher than I-value by --67%, --30%, +50%, +100%. For the convenience of calculations one can use the following formulas: A = I x 0.33, B = I x 0.7, C = I x 1.5, D = I x 2.0.

A-values are coincided with the recommendations of Food and Agricultural Organization (15).

Lipids (include 8 nutrient parameters)
Saturated fatty acids(SFA), Monounsaturated fatty acids(MFA) and Polyunsaturated fatty acids(PFA)are presented in AADN-tables as % of Energy. I-values for these three nutrients are calculated by multiplying Lipids’ I-value by 0,20 for SFA, by 0,50 for MFA and by 0,30 for PFA. A-, B-, C- and D-values are lower and higher than I-values by

--50%, --25%, +50% and +100% correspondingly.

Linoleic acid(Lin)(as % of Energy). I-value is calculated by multiplying PFA’s I value by 0.75. A-, B-, C- and D-values are lower and higher, than I value by --50%, --25%, +50% and +100%.

Cholesterol(Chol)(in mg). I-value is 200 mg. A-, B-, C- and D-values are lower and higher, than I-value by --70%, --50%, +50% and +100% correspondingly.

PFA/SFA ratio(P/S). I-value is 1.50. A-, B-, C- and D-values are lower and higher than I value by --50%, --25%, +50% and +75%.

n-3/n-6 ratio(3/6).This is the ratio (n-3)PFA/(n-6)PFA. I-value is 0.33. A-, B-, C- and D-values are lower and higher, than I-value by

--75%, --50%, +100% and +200% correspondingly.

Alcohol(Alc)(as % of Energy). The consumption of alcohol is regarded to be safe, if not in access 1 or 2 drinks per day. That is why A-, B-, C- and D-values in grams are 0, 0, 30, 60. AADN-tables presents corresponding values as % of Energy. We consider, that energy content of 1 g of Alcohol is 7 kCal.

Carbohydrates (include 5 nutrient parameters),Vitamins (include 14 nutrients), Elements (include 15 nutrients).

A-, B-, C-, D-, I-values for these nutrients for Standard model are presented in Table 1.

RESULTS & DISCUSSION

Modern program
42 Versions of Anti-Aging Dietary Norms (food allowances) were developed by now in Anti-Aging Center, Budapest in a form of AADN-tables: 7 versions were developed for Standard model (900, 1200, 1500, 1700, 2000, 2200 and 2500 kCal), 9 versions - for Diabetic model (900, 1300, 1500, 1600, 1800, 2100, 2200, 2300 and 2400 kCal), 17 versions - for Gastroentheropaty model (900, 900LF, 1100, 1100LF, 1300, 1500, 1500LF, 1700, 1700LF, 1900, 1900LF, 2100, 2100LF, 2300, 2300LF, 2500 and 2500LF kCal. LF - means low-fiber content), 9 versions - for Ischemic Heart Disease & Hypertension model (1000, 1100, 1200, 1400, 1600, 1800, 1900, 2100 and 2300 kCal). All tables’ values are in good correspondence with modern views of diet - health relationships (17). Table 1 presents only 1(one) of 42(forty two) AADN-tables - 2000 kCal Standard model. Other 41(forty one) versions of AADNs are stored in Anti-Aging Center, Budapest.

A-, B-, I-, C- and D-values of AADN-tables are based on thorough investigation of modern scientific literature on biology of aging and human nutrition. We intentionally digress from discussing every of 58 particular nutrient figures included in Table 1 since we consider that present work will encourage professional discussion among nutritional experts, dietitians, biologists and gerontologists, who may revise these values. Every interested scientist is welcome to join our International Anti-Aging Expert Commission to revise and modify A-, B-, C- and D-values, presented in Table 1. as well as of values that are included in other 41 AADN-tables. Discussion on data presented in this paper have to yield a joint comprehensive view on the problem of designing universal anti-aging nutritional criteria - ANTI-AGING DIETARY NORMS and in final will provide public with a new and improved version of AADN-tables. AADN-tables have to be a theoretical basis for the developing of various anti-aging diet rations.

Original computer program was developed in Anti-Aging Center, Budapest to help design Personal Diet Plans. Using certain version of AADN and with the help of food composition list a trained computer’s user can readily design individually adjusted Anti-Aging Diet Plan. Results of such a design for 2000 kCal Standard model version of AADN are presented on fig. 1. Nutrient’s composition of this Diet Plan is presented on fig 2. This Diet Plan (Fig. 1.) is only one of many possible computer’s work outs. Using AADN-tables anyone can be challenged to design their own individual Diet Plans according to their own personal taste. Recipes, included in Diet Plan are easy and fast cooking. Usually when daily energy intake is lower than 2300 - 2500 kCal Diet Plan must be enriched by vitamin and mineral supplements. In the Anti-Aging Diet Plan presented on Fig. 1 majority of 58 essential nutrients are being within the optimum range - between Low Optimum value (B) and High Optimum value(C). One can found from Fig. 2 that 49 of 58 nutrient parameters (85% of nutrients that were monitored) are lying within the Anti-Aging optimum range. We consider that in order to achieve adequate anti-aging protective effect of diet it is quite sufficient that vitamins and elements (totally 29) have to be between “minimum required value” (A) and “high optimum value” (C). Other nutrients - main, amino-acids, lipids, carbohydrates (totally 29) - should be more strictly balanced within Anti-Aging optimum range (between values B and C). Generally when 3/4 of nutrients are within optimum anti-aging range such a diet is regarded to be a diet with high degree of “balancing quality”.

Diet Plan (Fig. 1) can be used by an average healthy person, who wants to improve its health status and decrease the rate of aging. Individuals, aggravated with certain chronic diseases or who predispose to certain type of pathology should use other than Standard model version of AADN-tables. Due to lack of space 41 versions of AADN are not presented in present paper.

After approvement and verification of AADN-tables by anti-aging specialists, dietitians, nutritionists, physicians, and other practitioners everybody can readily and with confidence use AADN-tables as a practical guidance for designing individually adjusted Anti-Aging Diet Plans.

Future program
Control on human aging can be achieved on two levels of supervision on entry to the body (entry monitoring) and inside the body (inside monitoring). In present paper we attempted to develop a method of control of essential nutrients enter our organism (entry monitoring). Next step one have to supervise essential biochemical entities inside the body (inside monitoring). Due to differences in genetics, individual physiology, physical activity, nutrient bioavailability, predisposition to certain diseases and due to environmental differences or style of living it is more desirable to check all essential nutrients inside human body (inside monitoring). We mean that blood composition must be analyzed with a view to maintain within optimum anti-aging ranges the concentration of the maximum possible number of nutrients - amino acids, carbohydrates, lipoproteins, cholesterol, vitamins, micro and macro-elements, as well as of the most important biologically active substances: hormones, proteins and other essential endogenic species. We must monitor the quality and quantity of human biochemical media. In case the parameters monitored happen to be beyond the special optimum limits, appropriate corrections will be made by way of purpose-oriented changes in the character of the diet, exercises or other factors. If necessary vitamins, minerals, geroprotectors, nootropes and other supplements may be introduced into the Anti-Aging Diet Plan. The precise supervision on human being (entry and inside monitoring) as well as the condition of caloric limitation undoubtedly will lead to an essential reduction of the rate of human aging and essential prolongation of human life span.

ACKNOWLEDGMENTS
This work was supported by Anti-Aging Center Inc. The authors wish to extend their appreciation to Dr. Roy L. Walford, Professor of the UCLA School of Medicine for his extremely valuable monographs on the dietary restriction and aging, that encouraged us to perform this work. We are grateful to my colleagues and experts for their valuable contribution and criticism, while preparing present 1-St. Edition of Anti-Aging Dietary Norms.

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Table 1. Anti-Aging Dietary Norm-table, 2000 kCal Standard model.