European Journal of Clinical Nutrition (2000) 54, Suppl 3, S77±S91 ß 2000 Macmillan Publishers Ltd All rights reserved 0954±3007/00 $15.00 www.nature.com/ejcn Mechanisms of changes in basal metabolism during ageing CJK Henry1* 1Department of Nutrition and Food Science, School of Biological and Molecular Sciences, Oxford Brookes University, Oxford, UK A considerable number of physiological functions are known to show a gradual decline with increasing age. However, the effects of ageing differ widely between organ systems. It is believed that basal metabolic rate (BMR) falls dramatically with age. These observations, largely based on cross-sectional surveys, are discussed in light of our present understanding of the biology of ageing. This paper reviews both the longitudinal and cross- sectional studies of BMR and presents evidence that the fall in BMR with ageing may be less dramatic than previously perceived. Indeed, some subjects may show an increase in BMR with ageing. The mechanism of changes in BMR during ageing will be discussed. Organ weight changes appear to have a profound impact on BMR. The use of BMR to predict total energy expenditure in the `old elderly' ( > 75 y) is unlikely to be of any practical use due to wide intra- and inter-individual variation in BMR. This wide intra- and inter-individual variation in BMR is due to illness, disease and other metabolic disorders seen in the elderly. Finally, the importance of measuring BMR in elderly populations for its use in clinical medicine will be discussed. Descriptors: aging; basal metabolic rate; body composition European Journal of Clinical Nutrition (2000) 54, Suppl 3, S77±S91 Historical overview The principle embodied in the surface law was that basal metabolism is a simple function of surface area. Hence, if It is no exaggeration to claim that the science of nutrition surface area was computed, basal metabolism could be was founded on the study of energy metabolism. Tata calculated. The surface law was to have a powerful and (1964) de®ned basal metabolism rate (BMR) as the sum dominant hold on the estimation of BMR for over half total of the minimal activity of all tissue cells of the body a century. While the surface law remained in¯uential under steady state conditions. Similarly, Mitchell (1964) amongst many physiologists during the early part of this commented that `the basal metabolism of an animal is the century, it also attracted considerable opposition, notably minimal rate of energy expenditure compatible with life.' from Benedict and his co-workers. Benedict's objections to Magnus-Levy coined the term Grundumsatz or `basal the surface law were both biological and practical. In 1915, metabolism' in 1899. This term was of great value to the Benedict had introduced the concept of `active protoplas- early investigators, as it emphasised the need to conduct mic mass', and approached the problem of metabolism, not experiments under strictly standardized conditions. Krogh from the perspective of heat loss, but heat production. (1916) proposed the term `standard metabolism' to circum- Thus, Benedict proposed that BMR was proportional to vent the erroneous impression that basal metabolism is the protoplasmic mass. However, on a practical level, it soon lowest resting metabolism, ie the lowest that could be became clear that the measurement and estimation of sur- obtained by an individual. Although the term `standard face area was far from easy and satisfactory. By 1916, metabolism' has not gained universal usage, the meaning of DuBois and DuBois were to admit that `the validity of the basal metabolism has been widely accepted. surface law rests on the accuracy of determining surface area in humans'. Despite this cautionary note, they then went on to develop the ®rst reference standards for BMR Review of early work on BMR standards and predictive based on surface area! equations The `basal metabolism', namely the total of heat production DuBois height ± weight formula chart under standardised conditions, is closely related to oxygen consumption. The view that heat is primarily produced in While surface area may be calculated using various anthro- an animal to keep warm was ®rst proposed by Bergman in pometric parameters, DuBois and DuBois (1916) produced 1843 (Lusk, 1928). Forty years later, Rubner presented an equation relating weight and height to surface area as `supportive' evidence by demonstrating that the heat pro- follows: duction in a living organism is directly proportional to the A W 0:425 Â H 0:715 Â 71:84 surface area. This was the origin of the famous `surface rule=law' of Rubner, which he explained in terms of where A surface area (cm2), W weight (kg) and homeothermy. H height (cm). This was derived from surface area measurements in *Department of Nutrition and Food Science, School of Biological and nine subjects ranging in body weight from 6 to 93 kg. Later, Molecular Sciences, Oxford Brookes University, Gipsy Lane, Oxford OX3 0BP, UK. Aub and DuBois (1917), applying the surface law, of heat loss published a table of BMR=m2=h from 14 to 80 y (Table E-mail: [email protected] 1). This table is still widely used despite being based on a Mechanisms of changes in BMR CJK Henry S78 group of only nine subjects and one cadaver. The values socio-economic status and levels of physical activity. consisted of a tabulation for males and females between Longitudinal studies (Rinder et al, 1975) have shown that 14 ± 80 y by 2 y periods from 14 ± 20 y, and by decades many physiological parameters remain relatively constant from 20 to 80 y. All values were expressed as Cal=m2=h. right through middle life, and show a decline at around The major criticism of the Aub and DuBois standards is the 70 ± 75 y. Without considering the additional issue of fact that the values only begin with subjects older than 14 y, sexual dimorphism in the rate and timing of the age-related and are too `general' for ages beyond 20 y. For example, changes in physiology and body composition (Chumlea & the BMR of a 20 and 39 y old man are the same, con®rming Baumgartner, 1989), as a ®rst approximation we may that the standards do not take into account the likely age- classify the elderly as: related changes in BMR. `young elderly' 65 ± 75 y `old elderly' > 75 y BMR and ageing This classi®cation may be a practical consideration Among the earliest to investigate energy exchange in when we attempt to measure and use BMR values to humans at various ages were Magnus-Levy and Falk, estimate total energy expenditure in these subjects. who in 1899, studied seven men. These results were subsequently used by Aub and DuBois (1917) to draw a stylized curve of the average level of metabolism at various Speci®c problems in the assessment of BMR in the ages (Figure 1). elderly At the time of this analysis, these authors commented on Benedict (1938) outlined a comprehensive list of conditions the paucity of data on subjects after the age of 43. In an to be imposed when BMR was to be measured. attempt to rectify this situation, Aub and DuBois (1917) These included the following: studied six men aged between 77 and 83 y. The subjects for the study came from a New York City home for the aged. 1. Absence of gross muscular activity. The authors commented that the subjects were `fairly well 2. Post-absorptive state. nourished, though on a plain and scanty diet'. This raises 3. Zone of thermoneutrality. the question of sample choice and selection of the elderly 4. Minimal emotional disturbance. for studies on BMR ± a point we shall return to later on. 5. Wakefulness. 6. Normal nutritional status. 7. Absence of disease or infection. Problems in the de®nition and classi®cation of the elderly Whilst these conditions may be relatively hard to comply with even in the young and middle aged, it is The term elderly, currently de®ned as 65 y or older, even harder to satisfy all these conditions in the elderly. encompasses a heterogeneous group with varying health, More importantly, conditions (1), (6), and (7) may be nearly impossible to achieve in all elderly subjects. For example, minor muscular movement appears to increase Table 1 DuBois normal standards for BMR (Cal=m2=h) BMR dramatically as shown in Table 2. Age (y) Males Females By de®nition, BMR is measured in the thermoneutral zone where there is no cold or heat stress to in¯uence 14 ± 15 46.0 43.0 metabolism. Little is known about the `thermoneutral zone' 16 ± 17 43.0 40.0 18 ± 19 41.0 38.0 in the elderly. For example Horvath et al (1955) found that, 20 ± 29 39.5 37.0 when young men were exposed to 10 C, this produced 30 ± 39 39.5 36.5 shivering and an increased metabolic rate but the elderly 40 ± 49 38.5 36.0 showed no response at all. Numerous studies have sug- 50 ± 59 37.5 35.0 gested an association between levels of physical activity 60 ± 69 36.5 34.0 70 ± 79 35.5 33.0 and BMR. Indeed, Poehlman and colleagues (Poehlman & Danforth, 1991; Poehlman, 1996; Poehlman, 1998) have Figure 1 Changes in BMR with age expressed as Cal=m2=h. European Journal of Clinical Nutrition Mechanisms of changes in BMR CJK Henry S79 Table 2 In¯uence of small muscular movements on oxygen Table 3 Measurements of basal metabolism in subjects over 50 y reported consumption at rest between 1899 ± 1936 O2 consumption Percentage Number of subjects by age group Activity (cm3=min) increase Date Authors Gender 50 ± 69 70 ± 89 > 90 Total Basal 188 ± - Arm movement 218 15.9 1899 Magnus-Levy & Falk M 2 4 0 6 Basal 189 ± - 1916 DuBois M 1 0 0 1 Arm movement 224 18.5 1917 Aub & DuBois M 0 6 0 6 Leg movement 209 10.6 1919 Harris & Benedict M 5 0 0 5 F142016 Adapted from Carpenter (1933).