Editors' ChoiceDiabetes

Aging metabolism: Evitable or inevitable?

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Science Translational Medicine  03 Feb 2016:
Vol. 8, Issue 324, pp. 324ec19
DOI: 10.1126/scitranslmed.aaf2006

Decades of research have begun to unravel the mysteries of how and why we age. For example, as we grow older we become less responsive to insulin, a hormone that regulates blood sugar. This condition, called “insulin resistance,” is important because it is a step in the progression to type 2 diabetes. With aging, we also begin to store fat in strange places, such as within our muscle or liver cells rather than within fat cells where it is intended to be stored. To add insult to injury, our mitochondria, the organelles that generate essential chemical energy, begin to fail at their jobs. All of these metabolic abnormalities are considered hallmarks of aging. However, this dogma is now being called into question: Are these metabolic derangements truly inevitable consequences of age, or do they simply reflect altered lifestyle with aging? This paradigm shift has been proposed previously, but a recent report in the journal Diabetes provides some compelling new evidence.

Chee and colleagues carefully evaluated insulin sensitivity and lipid metabolism in young and older adults. What makes this study unique is that the young and older subjects were matched for habitual physical activity levels and body composition. A separate group of overweight older adults were compared with lean older adults with similar lean mass. With this study design, the authors were able to provide some interesting new insights into the extent to which metabolic abnormalities are due to aging, independent of the influence of lifestyle factors. They found that only overweight older adults exhibited insulin resistance and lipid accumulation in their muscles. There were no differences between young and older adults who were matched for body composition and physical activity. These data are encouraging because they suggest that some age-related metabolic changes may not be inevitable. The news is not all good, however. This study also shows that even lean older adults exhibit changes in adipose tissue lipolysis such that they have greater release of lipids from fat cells into circulation. This increased lipid availability may predispose older adults to accumulate fat in skeletal muscle and liver when they become physically inactive. The study reinforces the importance of physical activity across the life span and also highlights the need for therapeutic strategies to target lipid metabolism in older adults.

C. Chee et al., The relative contribution of intramyocellular lipid to whole body fat oxidation is reduced with age, but subsarcolemmal lipid accumulation and insulin resistance are only associated with overweight individuals. Diabetes 10.2337/db15-1383 (2016). [Abstract]

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