**2. Age changes of basal metabolism**

Methodological requirements for basal metabolism measuring are hard to be implemented outside a clinic, therefore metabolism in a state of rest is most commonly measured (lying down, comfortable temperature, 2-4 hours after food intake, without any stress factors), which is approximately 10-20% more than the level of basal metabolism. Present-day children have resting metabolism values even lower than standard norms of basal metabolism (Kornienko, 1979), proposed by Harris and Benedict (1919), which might be the result of acceleration of growth and development, observed up to the 1980s (Godina, 2009). With age the rate of resting metabolism (per body mass unit) is reduced – from infancy to the adulthood– by 1.5 – 2 times. The reasons for this reduction have been discussed for the last 150 years.

Since Max Rubner's time (1883) it has been known that as mammals gain body mass, heat production per mass unit is reduced, while the metabolism rate, relative to the surface space, is practically constant ("the rule of surface"). These metabolism changes were primarily explained by thermoregulation expenditure, but it turned out that in a thermoneutral conditions, without any extra heat production, this alignment persists. Moreover, this relation between metabolism rate and body size is observed in invertebrates (Schmidt – Nielsen, 1987; Ivanov, 1990).

Energy Metabolism in Children and Adolescents 123

metabolism even during rest— 300 kcal/kg/day. At the same time, the muscle tissue whose relative quantity is almost doubled in the period of postnatal development, is characterized

It should be noted, that the dynamics of age changes in resting metabolism is not just a simple decrease in metabolism rate. As it is given in Fig. 1, periods characterized by a rapid decrease in metabolism rate, are replaced by age intervals where resting metabolism values are stabilized (Kornienko, 1979; Kornienko & Gohblit 1983; Kornienko et al, 2000). Taking this into consideration, a close correlation of changes in metabolic rate and growth velocity is found. Columns in Fig. 1 show relative annual increase in body mass. Turns out that, excluding the first year after birth, the higher the relative growth velocity, the higher the rate of resting metabolism lowering during this period. Inhibition of growth processes at the age of 1.5-2 coincides with the highest values of resting metabolism, and the increase in growth velocity by ages 6 through 7 is accompanied by a considerable decrease in metabolism. After this there is the next inhibition of growth, during which the level of metabolism is stabilized, and the next value decrease coincides with a new acceleration of growth processes. The last peak of resting metabolism is observed at about the age of 14 years, before the puberty growth spurt, and soon after that the energy metabolism rate is stabilized on the level typical for adults. According to longitudinal observations, all these changes are typical both for boys and girls, but in girls they are usually observed 0.5-1 years

Rate value of basal metabolism is especially important for diagnosing and treating several endocrinological diseases, as well as obesity. Because of that there are ongoing discussions in scientific literature about methods of calculating basal metabolism values using various formulae – Harris & Benedict (1919), the WHO committee and others (White & Seymour, 2005; Frankenfield et al., 2005; Garrel et al., 1996; Hayter & Henry, 1994; Tverskaya et al., 1998, etc.). Most contemporary authors consider the volume of cellular mass or the value of lean body mass the most important factor, as well as age, sex, constitution, race and ethnicity (Bosy-Westphal et al., 2009; McDuffie et al., 2004; St-Onge & Gallagher, 2010; Vermorel et al., 2005).

Fig. 1. Dynamics of growth velocity and basal metabolic rate in children from birth to

by a very slow resting metabolism rate — 18 kcal/kg/day.

earlier (Kornienko & Gohblit, 1983).

maturity (after: Kornienko, 1979; modified)

For a long time the increased metabolic rate in infants has been attributed to metabolic expenditure on growth (Karlberg, 1952). But this hypothesis was not corroborated by facts. An infant's growth is most intense in the first 6 months after birth. The growth coefficient during this period is 4.0 (Schmal'hausen, 1935). At one year after birth, the coefficient is sharply reduced, by more than 10 times - to 0.3. Basal metabolism rate is at its peak at the age of one. Special calculations (Kornienko & Gohblit, 1983) proved that true expenditure on synthesis, associated with growth processes, even in the first 3 postnatal months, when the infant's growth velocity is at its peak, is no more than 20 kcal /day, which is 7—8% of the total expenditure. According to King et al. (1994), total energy expenditure of a woman body during pregnancy is on the average 325 MJ (77621 kcal). It is approximately a 20% increase in metabolism rate, compared to basal energy expenditure of a female. Evidently most of this energy expenditure is the expenditure on extra functions of maternal body systems, including the ones associated with the required adaptation to the increased physical load: during the second half of the pregnancy period the condition of the mother is bearing an extra load weighing from 2-3 kg to 10-12 kg (that includes the weight of the foetus, placenta, amniotic fluid, grown uterus, etc.). In fact, the growth processes takes a small part of the volume of energy expenditure. The energy expenditure on proliferative processes of kids older than one year is even less (under 1%), when the growth velocity becomes 12-15 times slower compared to intrauterine period.

Empiric formulae are used to express the relation between body size and metabolic rate. Kleiber (Kleiber, 1961) proposed the following formula for mammals, including humans:

$$\mathbf{M} = \mathbf{67.7} \bullet \mathbf{P}^{0.75} \text{kcal } / \text{day} \tag{1}$$

Where M is the heat production of the whole body, and P is body mass.

But age changes in basal metabolism cannot be calculated using this equation. During the first year after birth, heat production is not reduced as required by the Kleiber equation, but stays on the same level or even increases, while the body mass during this period is tripled. Only one year after birth is the metabolism rate of 55 kcal/kg per day reached, "proposed" by the Kleiber equation for the body with the mass of 10 kg.

Only after 3 years does the basal metabolic rate starts to gradually reduce, and reaches the level of an adult person (25 kcal/kg per day) only during puberty.

Increase in the basal metabolic rate within the first year of an infant's life is correlated by some authors with a decrease in volume of intracellular space in most tissues. According to Brück (1970), if the oxygen consumption rate per mass unit of newborn infants in rest is 5.0 ml O2/kg/min, and in one-year infants — 8.2 ml O2/kg/min, then recalculated per an active cellular mass unit, it turns out that a newborn consumes 9.0 ml O2/kg/min, and a one year-old child— 10.9 ml O2/kg/min.

Rate of basal metabolism starts reducing from the age of three (Fig. 1). The first place among the probable reasons for this phenomenon is change in body composition correlated with age – increase in relative mass of tissue with a small rest metabolism rate (bone tissue, fat tissue, skeletal muscles, etc.). M. Holliday (1971) has already proven that a gradual decrease in the metabolism rate of children can be easily explained by the uneven growth of organs, presuming that the metabolic rate of tissue growth in the process of postnatal development is constant. For instance, it is known that mass of the brain (which greatly contributes to the level of basal metabolism) for newborns is 12% of their body mass, while in adults it's only 2%. Internal organs (liver, kidneys, etc.) also grow unevenly, and have a high level of energy

For a long time the increased metabolic rate in infants has been attributed to metabolic expenditure on growth (Karlberg, 1952). But this hypothesis was not corroborated by facts. An infant's growth is most intense in the first 6 months after birth. The growth coefficient during this period is 4.0 (Schmal'hausen, 1935). At one year after birth, the coefficient is sharply reduced, by more than 10 times - to 0.3. Basal metabolism rate is at its peak at the age of one. Special calculations (Kornienko & Gohblit, 1983) proved that true expenditure on synthesis, associated with growth processes, even in the first 3 postnatal months, when the infant's growth velocity is at its peak, is no more than 20 kcal /day, which is 7—8% of the total expenditure. According to King et al. (1994), total energy expenditure of a woman body during pregnancy is on the average 325 MJ (77621 kcal). It is approximately a 20% increase in metabolism rate, compared to basal energy expenditure of a female. Evidently most of this energy expenditure is the expenditure on extra functions of maternal body systems, including the ones associated with the required adaptation to the increased physical load: during the second half of the pregnancy period the condition of the mother is bearing an extra load weighing from 2-3 kg to 10-12 kg (that includes the weight of the foetus, placenta, amniotic fluid, grown uterus, etc.). In fact, the growth processes takes a small part of the volume of energy expenditure. The energy expenditure on proliferative processes of kids older than one year is even less (under 1%), when the growth velocity becomes 12-15 times

Empiric formulae are used to express the relation between body size and metabolic rate. Kleiber (Kleiber, 1961) proposed the following formula for mammals, including humans:

But age changes in basal metabolism cannot be calculated using this equation. During the first year after birth, heat production is not reduced as required by the Kleiber equation, but stays on the same level or even increases, while the body mass during this period is tripled. Only one year after birth is the metabolism rate of 55 kcal/kg per day reached, "proposed"

Only after 3 years does the basal metabolic rate starts to gradually reduce, and reaches the

Increase in the basal metabolic rate within the first year of an infant's life is correlated by some authors with a decrease in volume of intracellular space in most tissues. According to Brück (1970), if the oxygen consumption rate per mass unit of newborn infants in rest is 5.0 ml O2/kg/min, and in one-year infants — 8.2 ml O2/kg/min, then recalculated per an active cellular mass unit, it turns out that a newborn consumes 9.0 ml O2/kg/min, and a

Rate of basal metabolism starts reducing from the age of three (Fig. 1). The first place among the probable reasons for this phenomenon is change in body composition correlated with age – increase in relative mass of tissue with a small rest metabolism rate (bone tissue, fat tissue, skeletal muscles, etc.). M. Holliday (1971) has already proven that a gradual decrease in the metabolism rate of children can be easily explained by the uneven growth of organs, presuming that the metabolic rate of tissue growth in the process of postnatal development is constant. For instance, it is known that mass of the brain (which greatly contributes to the level of basal metabolism) for newborns is 12% of their body mass, while in adults it's only 2%. Internal organs (liver, kidneys, etc.) also grow unevenly, and have a high level of energy

Where M is the heat production of the whole body, and P is body mass.

by the Kleiber equation for the body with the mass of 10 kg.

level of an adult person (25 kcal/kg per day) only during puberty.

M 67.7 • P kcal /day 0.75 (1)

slower compared to intrauterine period.

one year-old child— 10.9 ml O2/kg/min.

metabolism even during rest— 300 kcal/kg/day. At the same time, the muscle tissue whose relative quantity is almost doubled in the period of postnatal development, is characterized by a very slow resting metabolism rate — 18 kcal/kg/day.

It should be noted, that the dynamics of age changes in resting metabolism is not just a simple decrease in metabolism rate. As it is given in Fig. 1, periods characterized by a rapid decrease in metabolism rate, are replaced by age intervals where resting metabolism values are stabilized (Kornienko, 1979; Kornienko & Gohblit 1983; Kornienko et al, 2000). Taking this into consideration, a close correlation of changes in metabolic rate and growth velocity is found. Columns in Fig. 1 show relative annual increase in body mass. Turns out that, excluding the first year after birth, the higher the relative growth velocity, the higher the rate of resting metabolism lowering during this period. Inhibition of growth processes at the age of 1.5-2 coincides with the highest values of resting metabolism, and the increase in growth velocity by ages 6 through 7 is accompanied by a considerable decrease in metabolism. After this there is the next inhibition of growth, during which the level of metabolism is stabilized, and the next value decrease coincides with a new acceleration of growth processes. The last peak of resting metabolism is observed at about the age of 14 years, before the puberty growth spurt, and soon after that the energy metabolism rate is stabilized on the level typical for adults. According to longitudinal observations, all these changes are typical both for boys and girls, but in girls they are usually observed 0.5-1 years earlier (Kornienko & Gohblit, 1983).

Rate value of basal metabolism is especially important for diagnosing and treating several endocrinological diseases, as well as obesity. Because of that there are ongoing discussions in scientific literature about methods of calculating basal metabolism values using various formulae – Harris & Benedict (1919), the WHO committee and others (White & Seymour, 2005; Frankenfield et al., 2005; Garrel et al., 1996; Hayter & Henry, 1994; Tverskaya et al., 1998, etc.). Most contemporary authors consider the volume of cellular mass or the value of lean body mass the most important factor, as well as age, sex, constitution, race and ethnicity (Bosy-Westphal et al., 2009; McDuffie et al., 2004; St-Onge & Gallagher, 2010; Vermorel et al., 2005).

Fig. 1. Dynamics of growth velocity and basal metabolic rate in children from birth to maturity (after: Kornienko, 1979; modified)

Energy Metabolism in Children and Adolescents 125

will have an effect basal metabolism of the whole body. Important qualitative changes in nervous and mental activity occur in children age 1-2, due to differentiation processes in neural tissue (Farber & Machinskaya, 2009; Tsekhmistrenko et al., 2009). Meanwhile it has been proven 40 years ago that tissue differentiation in ontogenesis always starts with mitochondria development and a more active oxidation metabolism (Macler et al., 1971;

Calculations by Kornienko (1979) have demonstrated that for humans the contribution of various organs to the basal metabolism is changes with age. The adult human brain accounts for 24% of basal metabolism, the liver for 20%, the heart for 10.2% and the skeletal muscles for 28%. A one-year old child's brain accounts for 53% of basal metabolism, while the skeletal muscles account only for 8%. The liver's contribution is about 18% (Fig.3).

Unlike basal metabolism, which is the minimum level of body energy expenditure, average daily metabolism includes the sum of all expenditures associated with the realization of various body functions. Food processing and digestion, thermoregulation and muscle activity are the most power-consuming functions. Unfortunately, there is almost no data in literature on the energy value of mental activity (not taking into consideration the indirect

Fig. 3. Age changes in contribution of various organs and tissues into the structure of human

basal metabolism (After: Holliday, 1971; Kornienko, 1979; modified)

**3. Energy supply for functions during ontogenesis** 

**3.1 Daily energy expenditure structure** 

calculations by Holliday, 1971).

Makhin'ko & Nikitin 1975).

Another factor might play an important role – the change in metabolic activity of tissues in a growing organism, that occurs with age (Conrad & Miller, 1956; Nagorny et al., 1963). To test this assumption, our laboratory researched age changes in the mitochondrial apparatus of various tissues (Demin, 1983; Kornienko, 1979). Using Chance's differential spectrophotometer we measured cytochrome **a** concentration, which is a terminal ferment of the oxidative chain of mitochondria, in tissue homogenates of Wistar rats during ontogeny (Fig.2). The higher cytochrome **a** concentration, the higher oxidation activity is developed by a given tissue under the influence of an appropriate stimulus, provided it is adequately supplied with substrates and oxygen. This data allows to compare not just the potential metabolic activity of various tissues, but also to observe its changes, including changes occurring with age.

Fig. 2. Cytochrome **a** concentration in tissue homogenates of Wistar rat during ontogeny (after: Kornienko, 1979; modified).

Brown adipose tissue has the highest potential metabolic activity, both in young and adult rats; the liver is second in potential. Both tissues are characterized by the fast rise of cytochrome **a** concentration at the age of 16-20 days, which can be explained by the fact that at that time young rats leave their nest and start their separate life, which requires the activation of thermoregulatory processes. The food type changes at the same age, which has an effect on cytochrome **a** concentration in the intestine tissue. When adulthood is reached, cytochrome content in all these tissues is considerably reduced.

Content of oxidation ferments in cardiac and lung tissues is the most stable – it stays almost unchanged with age. But oxidation ferments in tissues of rat kidneys and brain increase approximately by a factor of 2.5 by adulthood. If the increase in tissue mass is considered, it turns out that the metabolic potential of brown adipose tissue during postnatal ontogenesis grows 10 times, the brain's - 11.4 times, the liver's –38.5 times, the kidney's –57 times, the skeletal muscles' –87 times. That directly affects the level and structure of energy metabolism.

It has been proven using this method (based on post-mortem materials from a trauma clinic) that cytochrome concentration is increased considerably in some grey matter areas in the brain cortex (4, 6, 10th and 17th fields according to Broadman), in the subcortical structures, and in the homogenates of children's whole brain at the age of 1—1.5, compared to the first months of life (Kornienko, 1979). Since at this age the human brain accounts for at least 50% of basal metabolism, it can be assumed that a more active oxidation processes of this tissue

Another factor might play an important role – the change in metabolic activity of tissues in a growing organism, that occurs with age (Conrad & Miller, 1956; Nagorny et al., 1963). To test this assumption, our laboratory researched age changes in the mitochondrial apparatus of various tissues (Demin, 1983; Kornienko, 1979). Using Chance's differential spectrophotometer we measured cytochrome **a** concentration, which is a terminal ferment of the oxidative chain of mitochondria, in tissue homogenates of Wistar rats during ontogeny (Fig.2). The higher cytochrome **a** concentration, the higher oxidation activity is developed by a given tissue under the influence of an appropriate stimulus, provided it is adequately supplied with substrates and oxygen. This data allows to compare not just the potential metabolic activity of various tissues, but also to observe its changes, including changes

Fig. 2. Cytochrome **a** concentration in tissue homogenates of Wistar rat during ontogeny

cytochrome content in all these tissues is considerably reduced.

Brown adipose tissue has the highest potential metabolic activity, both in young and adult rats; the liver is second in potential. Both tissues are characterized by the fast rise of cytochrome **a** concentration at the age of 16-20 days, which can be explained by the fact that at that time young rats leave their nest and start their separate life, which requires the activation of thermoregulatory processes. The food type changes at the same age, which has an effect on cytochrome **a** concentration in the intestine tissue. When adulthood is reached,

Content of oxidation ferments in cardiac and lung tissues is the most stable – it stays almost unchanged with age. But oxidation ferments in tissues of rat kidneys and brain increase approximately by a factor of 2.5 by adulthood. If the increase in tissue mass is considered, it turns out that the metabolic potential of brown adipose tissue during postnatal ontogenesis grows 10 times, the brain's - 11.4 times, the liver's –38.5 times, the kidney's –57 times, the skeletal muscles' –87 times. That directly affects the level and structure of energy metabolism. It has been proven using this method (based on post-mortem materials from a trauma clinic) that cytochrome concentration is increased considerably in some grey matter areas in the brain cortex (4, 6, 10th and 17th fields according to Broadman), in the subcortical structures, and in the homogenates of children's whole brain at the age of 1—1.5, compared to the first months of life (Kornienko, 1979). Since at this age the human brain accounts for at least 50% of basal metabolism, it can be assumed that a more active oxidation processes of this tissue

occurring with age.

(after: Kornienko, 1979; modified).

will have an effect basal metabolism of the whole body. Important qualitative changes in nervous and mental activity occur in children age 1-2, due to differentiation processes in neural tissue (Farber & Machinskaya, 2009; Tsekhmistrenko et al., 2009). Meanwhile it has been proven 40 years ago that tissue differentiation in ontogenesis always starts with mitochondria development and a more active oxidation metabolism (Macler et al., 1971; Makhin'ko & Nikitin 1975).

Calculations by Kornienko (1979) have demonstrated that for humans the contribution of various organs to the basal metabolism is changes with age. The adult human brain accounts for 24% of basal metabolism, the liver for 20%, the heart for 10.2% and the skeletal muscles for 28%. A one-year old child's brain accounts for 53% of basal metabolism, while the skeletal muscles account only for 8%. The liver's contribution is about 18% (Fig.3).
