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Changes In Glucose Metabolism May Define Aging

4 months, 3 weeks ago

1859  0
Posted on Jul 17, 2019, 2 p.m.

This study describes a new aging clock that is based on the changes of glucose catabolism in aging which is able to predict the age of an individual, and was able to show mutations identified in peripheral blood cells of aged subjects are statistically correlated with degenerative diseases. 

Aging is a physiological process that determines a progressive decline, several alterations contribute to the process including oxidative stress, deregulated autophagy, epigenetic modifications, and telomere shortening which may be so linked with the aging process that is may be possible to predict age based on the modification of one specific pathway. 

This aging clock is based on DNA methylation because energy metabolism changes are involved in the aging process; modifications of glucose catabolism and biochemical analyses were performed on mononuclear cells isolated from peripheral blood obtained from healthy people between the ages of 5-106. 

 ATP/AMP ratio, lactate dehydrogenase activity, malondialdehyde, and oxidative phosphorylation function and efficiency were evaluated, a machine learning based mathematical model was developed based on these biochemical markers that was able to predict age with a mean absolute error of approximately 9.7 years. Resulting non-invasive tool can evaluate and define age that could be used to evaluate effects of drugs of other treatments/interventions on early aging or rejuvenation.

This work is based on energy metabolism changes that occur with aging; MNC results show glucose metabolism shifts from aerobic to anaerobic with age and influences cellular energy status. Data shows during aging oxygen consumption isn’t completely coupled with ATP synthesis, determining reduction of ATP availability and making it more difficult to AMP recycling through enzymes regulating energy balance. 

Uncoupling status of OXPHOS machinery determines and increment of ROS production demonstrated by high MDA levels observed after the 60s and later decades triggering a vicious cycle in which damage to the inner membrane of mitochondria induces an increment of oxidative stress and relative structural failures. Attempts to restore ATP levels was observed in increment of LDH activity, possibly to convert NADH to NAD+ to restore the correct pool of oxidized coenzymes; LHD increment is not a choice for the cell rather a unique alternative to produce ATP from glucose. 

The critical period is between 50-60 decades based on data, subsequently energy metabolism continues to change but more slowly to stabilize after reaching 80; this may depend on if over 60 the level of oxidative stress is too high to become critical for integrity of the cell structure, determining a damage. Mild inhibition of mitochondrial respiration has been shown to extend lifespan in several species, therefore it is possible to speculate around the 30s-40s the increment of oxidative stress production could be considered favoured to drive towards cell proliferation devoted to renewal. But the increment of cellular proliferation requires energy and increases mitochondrial metabolism and relative oxidative stress production, reaching a critical amount that determines aging in the later decades. 

This model represents a new non-invasive tool to evaluate and define age on the basis of biochemical bioenergetic markers that may help to evaluate the effects of drugs or other interventions on early aging or rejuvenation. 

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This article is not intended to provide medical diagnosis, advice, treatment, or endorsement.

https://www.nature.com/articles/s41598-019-46749-w

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