Is Cell Regeneration Diet Specific?
Sunday, October 24th, 2010
By Amy Price PhD
Regenerative and preventive medicine can have an impact on quality of life by reducing neurodegeneration, optimizing the genetics we are dealt and by giving us the best shot at deflecting the damage trama has created. It appears that balance provides keys to longevity. It is tempting to chase after the newest ‘super antioxidant’ , cell treatment, medical device or pharmaceutical in hope of the cure. The most exciting concept is the power of the human body to heal from the inside out. I have noted the mostly mediocre results of multitudes of patients who have tried to juice their way to health, get injections of souped up grown out stem cells, live life in altered oxygen environments and inject chemical concoctions in hopes of staving off destruction.
Recently I was invited to join the herd of hardcore calorie restriction regimes. I did a little study on this and the results were interesting. There may be a slight bias here since I possibly value dark chocolate above hard science and only wish it was included as a food group! The study of interest was not hard core starvation but simply allowed animals to eat without limits and then the maximum amounts were reduced by 30% over a lifetime. None of the animals were underweight, they were allowed what was optimal for survival nothing more. A team of miners trapped underground in Chile were fed the same way and when they were rescued they were in remarkably good shape. The impact of diet restriction and not starvation is illustrated by the monkey study below:
The longitudinal Rhesus monkey (RM) study is an adult-onset study from 1989+ which explored the effects of 30% Caloric restriction (CR) without malnutrition on RM (Colman, Anderson, Johnson, Kastman, & Kosmatka 2009). Metabolic disorders and rising obesity incidence rates are complicated by the drive to eat until satiation is reached. Sedentary lifestyles, stress and environmental are contributing factors (Mattson, & Magnus, 2006). Resistance to age related illness and mortality in RM was addressed. A 5 page journal submission necessitates sharing selectively when considering research spanning 20 year+. Earlier CR research used rodents, mice, worms, flies, and yeast, however small human studies name CR as a factor for cardiovascular benefits (Colman et al, 2009).
The 30 mature male monkey study (1989) was expanded to include 30 females and an additional 16 males (1994) to increase statistical power and enable gender CR effects. RM matures at 7-14 years with mean lifespan of 27 years in captivity and 40 years in the wild. In 2009, 50% of controls and 80% of the CR group were still alive (Colman et al, 2009). CR was found to delay onset and reduce incidence of diabetes, cardiovascular disease, cancers and specific grey matter (GM) brain atrophy. Slowing or reversing the ageing process as evidenced by CD, metabolic disorders and neoplasms could benefit the economy. CR induced metabolic reorganization and regulation may reveal significant cross species metabolism regulatory factors and inform future research on life-span and quality life.
Ageing effects in yeast, worms, flies or mice CR studies indicate molecules responsible for signalling including mTOR,PGC-1a and SIRT1 are sensitive to nutrient changes (Colman et al, 2009). These mechanisms were introduced but not addressed in the study. They are thought to optimize mitochondrial function by improving synaptic function. These findings will be important if found to apply to primates and then humans (Colman et al, 2009) CR animals (below) looked younger and healthier at 27.6 years than controls as noted by thicker fur, elastic skin, posture, eye clarity, skin colour oxygenation, bone density seen through shoulders/hips/spine/jaw and less joint swelling in CR animals. See photo top left.
Subjective evidence was augmented by decreased mortality rates and age related conditions in CR protocols for RM. Figure 2 shows glucose impairment was not present in CR animals, cancer and CD were reduced. CR reduction correlating with lower glucose impairment/neoplasia/CD rates would be valuable to determine for later correlation in human studies. Diagram B (3) shows CR age related deaths 1:3 ratio. Figure C (4) shows all deaths. The higher non disease related deaths of CR animals to approximately age 20 is of concern and may be why CR effects on overall mortality failed to reach significance (p=0.16). The ratio of age related differences in mortality in contrast to this insignificance warrants further investigation.
Age associated diseases in RM are consistent with human ageing processes specifically glucose impairment, cancers and heart disease. Assessments included nutrient intake, BMI, blood pressure, activity levels, endocrine, serum, glucose level profiles and necropsy. Animals were observed 2x daily. They had regular electrocardiograms, brain MRs, and x-rays (Colman et al, 2009). Inclusions of EEG, echocardiogram and MRI colonoscopy could yield improved preliminary disease results. Stress echo may yield early cardiac valve impairment and angiography stroke inducing blockages. EEG could measure temporal aspects of brain function and determine if impaired timing resulted in attention, coordination or processing deficits. Colonoscopy could explore whether early treatment or CR affected survival rates.
Lean muscle mass and metabolic function was preserved in CR animals. Pre-diabetic conditions at baseline resolved in the CR condition. Neoplasm incidence and cardiovascular disease were reduced by 50% with CR. Human age related brain atrophy isn’t accurately replicated using small animals (Colman et al, 2009). Higher cognition, state/trait differences, working memory capacity and variances in somatosensory architecture complicate parallels between animal and human studies (Yankner& Loerch,2008). Common grey matter atrophy patterns exist so (GM) volume was measured. Age related cortical and temporal atrophy was resistant to CR. Significantly less age related atrophy was found in areas of executive function and motor pathways (Colman et al, 2009).
It is not known if genomics were applied to recruit genetically dissimilar animals to constitute a random population although animals were assigned to CR or control in a random manner. Diet was individualized in reference to volume consumed. We are not told if animals were allowed to graze or if food was given at specific times nor was there information given on sleep times and cycle differences (Froy & Miskin, 2010). This may influence insulin levels, circadian rhythms and preferred amount consumed per meal (Mattson, Chan, Duan, Aging, Joseph, Cole, G., et al. 2009). Nutritional needs over lifespan and personal variations in nutrient type were not identified (Mattson & Magnus, 2006). In animals requiring medical treatment, information was not forthcoming in relationship to drug/strategy interactions on factors measured (Heading, 2008). Libido/fertility levels with CR and CR effects on offspring DNA were not discussed.
Identification of longevity factors for RM not in captivity and whether CR benefits are tied to lifetime commitment or are developmentally sensitive would be useful for future study. Specific restriction of foods/groups such as high fats and sugars may be as beneficial as CR (Molteni, Barnard, Ying, Roberts & Go, 2002). Linking CR application to specific phenotypes may increase CR effects (Prolla & Mattson, 2001). The higher incidence of premature deaths in CR animals could be investigated by comparing vestibular and motor function of CT animals with controls.
Although this study may inform human ageing research, cross-species generalizations need cautious application. Human variations in genomics, phenotypes, complex cognition, stressors, diet, social responsibilities and exercise may mean successful RM studies do not transfer to humans (Carlson, 2007). It still may be reasonable to consider CR in order to enjoy the possible subjective and objective benefits described in the study.
References:
Carlson, N. R. (2007) Physiology of Behaviour, 9th edn, Pearson International, Allyn & Bacon, Boston.
Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, llison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R. ‘Caloric restriction delays disease onset and mortality in rhesus monkeys’. Science. 2009; 325:201‐204
Froy, O., & Miskin, R.(2010). Effect of feeding regimens on circadian rhythms : Implications for aging and longevity. Review Literature And Arts Of The Americas, 2(1), 7-27.
Heading, C, (2008) ‘Addiction potential of medicinal drugs’, GUIDE TO ADDICTION, 1-47.SD805 (eds) ,2009, Open University, UK, Milton Keynes
Mattson, M. P., & Magnus, T. (2006). ‘Ageing and neuronal vulnerability’. Neuroscience, 7(April). doi: 10.1038/nrn1886.
Mattson, M. P., Chan, S. L., Duan, W., Aging, B., Joseph, J., Cole, G., et al. (2009). Modification of Brain Aging and Neurodegenerative Disorders by Genes , Diet , and Behavior. Physiological Reviews, 637-672.
Molteni, R., Barnard, R. J., Ying, Z., Roberts, C. K., & Go, F. (2002). A High-Fat , Refined Sugar Diet Reduces Hippocampal Brain-Derived Neurotrophic Factor , Neuronal Plasticity ,. Science, 112(4), 803-814.
Prolla, T. A., Mattson, M. P., Prolla, T. A., & Mattson, M. P. (2001). Molecular mechanisms of brain aging and neurodegenerative disorders : lessons from dietary restriction. Review Literature And Arts Of The Americas, 24(11), 21-31.
Yankner BA, Lu T, Loerch P. Annu Rev Pathol 2008;3:41.
Figure 1 A&B are control animals C&D are CR all at 27.5 years (Colman et al 2009)Figure 1 A&B are control animals C&D are CR all at 27.5 years (Colman et al 2009)
