All Stem Cells Japan

The inverse association of cancer and Alzheimer's: a bioenergetic mechanism(2013)

Lloyd A. Demetrius and David K. Simon
The sporadic forms of cancer andAlzheimer’s disease (AD) are both age-related metabolic disorders. However, the molecular mechanisms underlying the two diseases are distinct: cancer is described by essentially limitless replicative potential, whereas neuronal death is a key feature of AD. Studies of the
origin of both diseases indicate that their sporadic forms are the result of metabolic dysregulation, and a compensatory increase in energy transduction that is inversely related. In cancer, the compensatory metabolic effect is the upregulation of glycolysis—the Warburg effect; in AD, a bioenergetic model based on the interaction between astrocytes and neurons indicates that the compensatory metabolic alteration is the upregulation of oxidative phosphorylation—an inverseWarburg effect. These two modes of metabolic alteration could contribute to an inverse relation between the incidence of the two diseases.We invoke this bioenergeticmechanismto furnish amolecular basis for an epidemiological observation, namely the incidence of sporadic forms of cancer and AD is inversely related.We furthermore exploit the molecular mechanisms underlying the diseases to propose common therapeutic strategies for cancer and ADbased on metabolic intervention.
 

1. Introduction

The vast majority of cancers and neurodegenerative disorders such as Alzheimer’s disease (AD) in the general population are sporadic in nature.
The monogenic forms of cancer and AD are relatively rare, less dependent on age and have proved genetic factors. The sporadic forms of the diseases are strongly age-related. The incidence of cancer increases exponentially with age, and it abates with age at very advanced ages. The incidence of AD also increases exponentially with age. In view of the age-dependence of these diseases and the dramatic increase in life expectancy during the last 25 years, there has been a tremendous increase in the number of individuals affected with both diseases. Cancer and AD represent increasingly common pathologies
with significant effects on human health and welfare.
 

7. Conclusion

The analysis in this paper contends that both cancer and AD are metabolic diseases—a predictable consequence of the process of ageing and the effect of metabolic instability.
Cancer is characterized by a metabolic shift—an upregulation  of glycolysis (the Warburg effect). AD is characterized by an inverse shift—an upregulation of OxPhos (the inverse Warburg effect).
The proliferation of cancer cells and the transition towards AD implicate a common mechanism—the entropic selection principle. This principle entails that the outcome of selection between cells using OxPhos and glycolysis will be predicted by the metabolic rate, which is positively correlated with evolutionary entropy, and contingent on the resource abundance and resource diversity: cells with upregulated OxPhos will have a selective advantagewhen resources are constant and limited,
whereas cells with upregulated glycolysis will be favoured when resources undergo large variation in abundance.
The entropic selection principle, when integrated with the metabolic processes underlying cancer and AD, predicts an inverse relationship between the incidence of the two diseases: individuals with cancer are less likely to develop AD in the future, and individuals with AD are less vulnerable to cancer. These predictions are consistent with recent epidemiological studies.
The elucidation of a common dynamic process underlying both sporadic forms of the disorders suggests a new class of therapeutic strategies for regulating the propagation of these diseases.
Source and See More : http://dx.doi.org/10.1098/rsif.2013.0006