Chronic Caloric Restriction Preserves Mitochondrial Function in Senescence without Increasing Mitochondrial Biogenesis

Maintaining a high abundance of mitochondrial DNA and reduced oxidative stress ameliorates age-related insulin resistance.

“maintaining a high abundance of mtDNA and reduced oxidative stress ameliorate age-related IR (6).”

Caloric restriction is known to improve insulin sensitivity and lessen mitochondrial redox stress, which lowers reactive oxygen species release.

“Thus, energy restriction that is well-known to enhance insulin sensitivity also reduces redox burden on the mitochondria, resulting in lower reactive oxygen species emissions (15).”

These adaptations appear to improve myocellular redox status through mechanisms similar to those previously reported in calorie-restricted mice.

“Together, these adaptations appear to improve the myocellular redox status through mechanisms similar to those that we previously reported preserved mitochondrial performance during senescence in lifelong calorie-restricted mice (15).”

Moderate reduction of calorie intake to 30-50% less than ad libitum without malnutrition can delay the onset of age-related diseases, improve stress resistance, and slow functional decline.

“Moderate reduction of calorie intake to 30–50% less than ad libitum without malnutrition can delay the onset of age-related diseases, improve stress resistance, and slow functional decline [70].”

Life-long 40% caloric restriction preserves mitochondrial capacity and efficiency in aged mice without substantially affecting mitochondrial biogenesis.

“Conversely, a study by Lanza et al. showed that life-long 40% caloric restriction preserves mitochondrial capacity and efficiency in aged mice without substantially affecting mitochondrial biogenesis [70].”

Lifelong caloric restriction in mice completely prevents age-related loss of mitochondrial oxidative capacity and efficiency without increasing mitochondrial content, suggesting CR preserves mitochondrial function by maintaining existing components rather than replacing damaged mitochondria.

“Lifelong CR in mice can completely prevent the age-related loss of mitochondrial oxidative capacity and efficiency without increasing mitochondrial content,152 suggesting that CR preserves mitochondrial function by maintaining its existing components, not by replacing damaged mitochondria with new mitochondria.”

CR increases mitochondrial coupling efficiency.

“Indeed, CR has been shown to decrease mitochondrial reactive oxygen species (ROS) production (Asami et al., 2008; Lanza et al., 2012), increase mitochondrial coupling efficiency (Lanza et al., 2012), and increase mitochondrial respiration per unit of mitochondria in aged muscles (Hepple et al., 2005, 2006).”

CR decreases mitochondrial reactive oxygen species production.

“Indeed, CR has been shown to decrease mitochondrial reactive oxygen species (ROS) production (Asami et al., 2008; Lanza et al., 2012), increase mitochondrial coupling efficiency (Lanza et al., 2012), and increase mitochondrial respiration per unit of mitochondria in aged muscles (Hepple et al., 2005, 2006).”

All studies reporting an aging-related decrease in IMF mitochondrial size only assessed mitochondrial morphology in longitudinal orientation.

“Importantly, all studies reporting an aging-related decrease in IMF mitochondrial size only assessed mitochondrial morphology in longitudinal orientation.”

A recent report indicates that caloric restriction enhances mitochondrial function without changes in mitochondrial content or biogenesis.

“Interestingly, a recent report indicates that CR enhances mitochondrial function without changes in mitochondrial content or biogenesis (Lanza et al, 2012).”

The effects of caloric restriction on mitochondrial function are not consistent across studies or across tissues.

“However, this is not consistent across studies or across tissues (Hancock et al., 2011; Lanza et al., 2012; Walsh et al., 2014).”