In his book, Beyond the 120 Year Diet: How to Double Your Vital Years, Dr. Walford describes Calorie Restriction as a method for extending maximum life span. Chapter 2 describes functional tests for estimating the rate of aging. He calls these the “biomarkers of aging” and divides them into categories for determining functional age, predictive value for remaining life expectancy, and disease susceptibility or segmental aging (p. 32).
Dr. Walford also mentions “biomarkers of success” which determine whether a person is successfully following a CRON diet. He says, “Are you really doing what it takes to retard aging or are you just playing around? You don’t have to wait six years to find the answer to this important question. Six months is time enough. Your doctor can do a number of tests before you start and then six months later, tests which show rapid changes if you are on track with the program, tests including levels of blood sugar, cholesterol, blood pressure, and a number of other parameters.”
With regard to metabolism, Dr. Walford describes a study of 54 farmers (p. 64) that revealed “metabolic efficiency, expressed as work done in relation to energy intake, was actually 80 percent higher for the ten farmers with the lowest intake (1,535 calories) than for those with the highest intake (2,382 calories). Heights and weights did not differ and the two groups performed the same amount of labor.” Dr. Walford goes on to say: “A major secret of health and longevity is to be always below your set point, maintaining yourself on a high enough quality diet that you are not deficient in any essentials, and to operate at maximum metabolic efficiency. This is, in fact, the central idea of my longevity program.”
In describing his experience in the Biosphere, Dr. Walford describes that Keys showed in the Minnesota experiment that 6 mo of severe energy restriction reduced the resting metabolic rate (RMR) in absolute terms by 39% or by 16% when expressed per kilogram of metabolically active tissue. A more recent study showed that a 40% CR diet for 21 days reduced BMR by 12%. Studies of anorexic patients, who are consistently calorically restricted, also demonstrate that their BMR is significantly lower than that of control subjects. One study found the BMR of anorexic patients to be lower by 20.8%, or by 11.5% after adjustment for fat-free mass.
BMR seems like a good biomarker for Calorie Restriction because it decreases within a few days of the onset of CR, and because it remains lower as long as CR is continued. The absolute value of the BMR in kJ/min may be a useful biomarker for determining whether you are “really doing what it takes to retard aging”.
 Roy Walford, M.D., “Beyond the 120 Year Diet: How to Double Your Vital Years”, 2000.
 Christian Weyer, Roy L Walford, Inge T Harper, Mike Milner, Taber MacCallum, P Antonio Tataranni and Eric Ravussin, “Energy metabolism after 2 y of energy restriction: the Biosphere 2 experiment”, American Journal of Clinical Nutrition, Vol. 72, No. 4, 946-953, October 2000.
 Friedlander AL, et al. “Three weeks of caloric restriction alters protein metabolism in normal-weight, young men” Am J Physiol Endocrinol Metab., 2005 Sep;289(3):E446-55. Epub 2005 May 3. PMID: 15870104
Nine young, normal-weight men [23 +/- 5 y, 78.6 +/- 5.7 kg, peak oxygen consumption (Vo2 peak) 45.2 +/- 7.3 ml.kg(-1).min(-1), mean +/- SD] were underfed by 40% of the calories required to maintain body weight for 21 days and lost 3.8 +/- 0.3 kg body wt and 2.0 +/- 0.4 kg lean mass. Protein intake was kept at 1.2 g.kg(-1).day(-1). BMR declined from 1,898 +/- 262 to 1,670 +/- 203 kcal/day.
 Polito A, Fabbri A, Ferro-Luzzi A, Cuzzolaro M, Censi L, Ciarapica D, Fabbrini E, Giannini D. Basal metabolic rate in anorexia nervosa: relation to body composition and leptin concentrations. Am J Clin Nutr. 2000 Jun;71(6):1495-502. PMID: 10837290
The BMR of AN patients (2.73 ± 0.37 kJ/min) was significantly lower than that of control subjects (3.45 ± 0.34 kJ/min) (P < 0.001), even after adjustment for FFM (2.92 ± 0.33 kJ/min in AN patients and 3.30 ± 0.26 kJ/min in control subjects; P < 0.004).