Calorie Restriction and Dwarf Mice in Gerontological Research

Abstract

What aging process is delayed by calorie restriction (CR) and mutations that produce long-lived dwarf mice? From 1935 until 1996, CR was the only option for increasing the maximum lifespan of laboratory rodents. In 1996, the mutation producing the Ames dwarf mouse (Prop-1^–/–) was reported to increase lifespan. Since 1996, other gene mutations that cause dwarfism or lower body weight have been reported to increase the lifespan of mice. The recent discovery of long-lived mutant dwarf mice provides an opportunity to investigate common features between CR and dwarf models. Both CR and dwarf mutations increase insulin sensitivity. Elevated insulin sensitivity reduces oxidative stress, a potential cause of aging. The elevation of liver insulin sensitivity by the hormone adiponectin in CR and long-lived dwarf mice can lower endogenous glucose production and raise fatty acid oxidation. Adiponectin reduction of plasma glucose in CR and long-lived dwarf mice can thereby lower age-related increases in oxidative damage and cancer.

From leptin to other adipokines in health and disease: Facts and expectations at the beginning of the 21st century

“…In this context, increased adiponectin levels are associated with extended longevity in mice [145][146][147][148]. Transgenic mice expressing high levels of human adiponectin have increased longevity [146] and various mouse models of extended longevity including fat-specific insulin receptor knockout mice [147], mice with defects in growth hormone production [148], and calorie-restricted mice [149] have increased adiponectin.…”

Dietary restriction, mitochondrial function and aging: from yeast to humans

“…Therefore, a conserved response to starvation stress is to accumulate carbon sources that would maximize long-term survival and to utilize them efficiently later in life [6]. Worth mentioning, one of the effects of CR in mammals is the elevation of liver insulin sensitivity by the hormone adiponectin, which lowers endogenous glucose production, diminishes reliance on glucose and its metabolites for energy, and raises fatty acid oxidation [144]. This switch in substrate utilization can reduce ROS generation at mitochondrial respiratory chain complex I and therefore, minimize oxidative stress.…”

Caloric restriction and its mimetics

“…However, it is still not clear whether the longevity extension effect of caloric restriction is dependent on the insulin/IGF signaling pathway. Flies containing the FOXO mutation still responded to caloric restriction (39), and the lifespan of long lived-Ames dwarf mice generated by mutation of growth hormone was also extended by caloric restriction (40).…”