This study characterizes RMR in a group of high clinical importance for whom very little information is available, women older than 80 including frail women living in the community. RMR displayed a large degree of variability of RMR among old-old women and deviation from the sample average value was associated with being clinically frail. The likelihood of frailty did not increase monotonically with increasing RMR. Instead, either a low or high RMR was associated with an increase in the odds of frailty status after adjusting for body composition, body temperature and ambient temperature, compared to the sample average RMR. The relationship between RMR and self-selected walking speed, a key constituent feature of frailty, confirmed the findings for the frailty status indicator as either very low or high RMR was associated with slower average self-selected walking speeds compared to the sample average. This main finding, the increased variability of RMR in old-old women, particularly among the frail, has implications for both clinical practice and understanding the clinical syndrome of frailty if it is replicated.
There may be limited clinical utility to the practice of using population-based equations to predict energy requirements and create nutritional recommendations for old-old adults. The equation thought to be best suited for prediction of energy requirements in older adults correlated very poorly with measured RMR and was markedly biased toward a higher RMR. Difficulty predicting energy requirement may be even more pronounced for hospitalized old-old adults who are acutely ill than for these subjects, who were examined at home. Mean RMR and variability similar to this study were found in an examination of women in a nursing home in Sweden, which reported a mean reliable RMR of 1174 kcal/d ±175 (range 810–1560) among 33 women with an age range of 67–102.(27
) The findings here are also consistent with increased between-subject variability in total energy expenditure previously noted in old-old community-dwelling adults compared to younger adults.(28
) Until more information is available for old-old adults, clinical practice may be better suited by examination of clinical indicators such as oral intake and loss of muscle than by an estimate of energy requirement.
The exploratory findings here that relate deviations from average of RMR to frailty suggest the possibility of distinct pathways that converge on the clinical phenotype of frailty.(5
) One is characterized by a relatively hypermetabolic state, which may be disease-related.(31
) In another pathway, acceleration of age-associated decline in metabolic rate may occur, leading to a low resting metabolic rate. The nonlinearity of the relationship between RMR and walking speed is consistent with numerous studies showing an inverse u-shaped association between activity energy efficiency and walking speed (as examples, see Weyand et al.(33
) or Bastien et al.(34
)). Indeed, more generally it appears that for physiologic variables reflecting homeostasis (arterial blood pressure; serum glucose concentration; serum cholesterol concentration; body mass index; etc.) values at either extreme are an indicator of impaired physiologic function.
Our data suggest this occurs even after controlling for loss of muscle mass, and may represent physiologic compensation to preserve precious energy stores. The causal mechanisms behind alterations in RMR are likely to involve highly complex and redundant neurologic and endocrine pathways. That metabolic regulation is highly complex is suggested by the resilience in good health of both body temperature and body composition to fluctuations in ambient temperature and caloric intake across immediate, short-term and long-term time intervals. Specifically, sympathetic nervous system activity is a fundamental modulator of metabolism that has been shown to be positively associated both with physical activity and muscle mass(35
) and with dysfunction of the cardiac left ventricle.(36
) Among endocrine organs affecting metabolism, the thyroid plays a central role as a modulator of metabolism, perhaps partly through an influence on sympathetic nervous system activity.(37
) However, a substantial line of research suggests the thyroid may also be essential to adaptive changes that occur in the face of reduced energy intake. Caloric restriction studies have identified changes in mitochondrial membrane content, as well as function of uncoupling proteins ,governed by thyroid hormone that create thermogenesis through a mitochondrial proton leak.(38
) Studies in young healthy humans have repeatedly shown that a negative energy balance leads to a lowering of thyroid hormone levels that is accompanied by a lower resting metabolic rate (RMR) not explained by changes in body composition.(40
) The causal link between thyroid hormone levels and RMR was further been strengthened by an experimental study displaying how small changes in the dose of thyroid hormone replacement therapy led directly to corresponding increases or decreases in RMR.(44
) An attempt to replicate the previously-reported associations between sympathetic nervous system activity, thyroid hormone and RMR is planned in this old-old sample.
These data, if they are confirmed, support the hypothesis that there is more than one point of entry into the frailty spiral, and the importance of ongoing efforts to identify subtypes of frailty that point to subtype-specific preventive interventions. Previous work in older adults mostly younger than 80 years has also suggested that body composition alone does not explain differences in RMR between older and younger adults.(45
The study findings should be considered with its limitations. These results were obtained from a small sample of mostly urban, community-dwelling women. While filling an important void, these results are preliminary and larger studies will be required to examine RMR among men and for subgroups defined by chronic diseases and medication use. The equipment used to measure RMR did not measure ventilation rate. The external validity of the findings is strongly limited even if it is supported indirectly by the literature noted above. The post-hoc nature of some analyses warrants that P values should not be interpreted as confirmatory and detailed longitudinal examination of RMR is necessary to establish causal pathways.
In summary, in exploratory analyses RMR displayed a large degree of variability of RMR among old-old women and deviation from the sample average value was associated with being clinically frail. Equations to predict RMR that are not validated in old-old adults appear to have little ability to inform the clinical management of nutritional status in old-old adults. Frailty in late life may be the result of more than one type of derangement of metabolism.