Renormalized Basal Metabolic Rate as a Biomarker of Aging
The research community is very interested in producing biomarkers that can accurately measure the progression of aging, and the variance in the pace of aging from individual to individual. In a world in which therapies to slow or reverse aging are being developed and tested, progress will be slow until such time as there are easy, cost-effective ways to measure the state of aging before and after a treatment. It is an important area of research. While a universal biomarker of aging, one that works equally well to assess any class of therapy to treat aging, is probably too much to hope for, given that aging is caused by many distinct processes, the diversity of efforts to produce such a biomarker of aging should nonetheless lead to useful tools as the field advances.
Recent aging theories have proposed various causative biomarkers such as reactive oxygen species, calorie restriction, telomere length, insulin signaling, mitochondrial (mt) DNA mutations, fatty acid composition of membranes, and methylation. To date, the validity of these biomarkers has been examined mainly by investigating their age dependency. However, they are not satisfactory for an accurate description of the aging process, and they seem to interact with each other in a complex way. Thus, it is essential to explain how these biomarkers can show that the survival curve and mortality rate are directly related to longevity. Indeed, the probability of survival drops markedly in individuals over the age of 80, and the mortality rate increases exponentially up to the age of 100.
We here propose a new biomarker to describe the mortality rate and survival curve of the elderly. The basal metabolic rate (BMR) has long been known to decline with age, in line with the Harris-Benedict equation (HBE), which is useful for statistical analysis of a large amount of data. The mass-specific BMR (msBMR; BMR per unit mass) confers the standard normalization of BMR to decrease the variation based on the body weight of individual persons. However, the obtained msBMR still varies among them. We developed an approach in which a universal metabolic rate function of age was derived by renormalizing the msBMR. The first renormalization was attained by incorporating the body mass index (BMI) into the HBE. Interestingly, the variation of the msBMR was thus markedly decreased. We further performed a second renormalization to remove the remaining variation due to individual height by a little readjustment of the BMI. As a result, the renormalized msBMR (RmsBMR) revealed an exponential decline with only age.
The RmsBMR is likely proportional to cellular metabolism and then to the mitochondrial number (mt density) within the standard cell. The mt density was found to decrease very slowly with age. The exponential decay form of this density was shown to be a solution of the transport equation for the mitochondrial dynamical fusion/fission flow. This decay form was proven to be based on the Markov process, although the basic mechanism behind the occurrence of the mitochondrial dysfunction has remained unresolved.