Caloric restriction versus drug therapy to delay the onset of aging diseases and extend life

Abstract

There are two firmly established methods of prolonging life. Calorie restriction (CR) using nutrient-rich diets to prolong life in lower animals, and life saving medications in humans to delay the development of the major diseases of middle and old age. These two approaches have different mechanisms of action. In rats, CR at 40% below ad libitum intake begun soon after weaning and continued until death, reduces body weight by about 40% and increases lifespan. There have been no lifelong CR studies performed on humans. However, in healthy adult human subjects about 20% CR over a period of 2-15 years, lowers body weight by about 20% and decreases body mass index (BMI) to about 19. This CR treatment in humans reduces blood pressure and blood cholesterol to a similar extent as the specific drugs used to delay the onset of vascular disease and so extend human life. These same drugs may act by mechanisms that overlap with some of the mechanisms of CR in retarding these pathologies and thus may have similar antiaging and life prolonging actions. Such drugs may be regarded as CR mimetics which inhibit the development of certain life shortening diseases, without the need to lower calorie intake. In developed countries, better medical care, drug therapy, vaccinations, and other public health measures have extended human life by about 30 years during the 20th century without recourse to CR, which is so effective in the rat. The percentage gain in human life expectancy during the 20th century is twice that achieved by CR in rat survival. However, rat longevity studies now use specific pathogen-free animals and start CR after weaning or later, thereby excluding deaths from infectious diseases and those associated with birth and early life. There is a need to develop CR mimetics which can delay the development of life-threatening diseases in humans. In the 21st century due to the human epidemic of overeating with a sedentary lifestyle, it may necessary to utilize CR to counter the aging effects of overweight. Since the greatest life-extending effects of CR in the rodent occur when started early in life, long-term antiaging therapy in humans should be initiated soon after maturity, when physiological systems have developed optimally.

Caloric restriction reduces age-related pseudocapillarization of the hepatic sinusoid

“…Reducing caloric intake delays the onset of agerelated diseases and increase maximum lifespan by between 20% and 40% in many species (Everitt et al, 2005). CR influences lipoprotein profiles and the onset of vascular disease in animal models ) and similar effects have replicated in short term studies in humans (Heilbronn et al, 2006).…”

Age‐Related Changes in the Liver Sinusoidal Endothelium

“…It has been recognized for more than 70 years that caloric restriction promotes longevity. In general, a reduction of caloric intake by about 40% (with appropriate nutritional supplementation and usually commenced after weaning) increases maximum life expectancy by about 40%, and this is associated with a delay in the onset of most age‐associated disorders 33 . Understanding the effects of caloric restriction is now a critical component of aging research 34,35 .…”

Life Extension by Calorie Restriction in Humans

“…This life‐prolonging effect of CR in the rat has been repeatedly confirmed and discussed extensively by later investigators 2 . Ten life‐long studies of specific pathogen‐free male rats on 40% CR showed mean life span to be extended by 24.7% 3 . CR over a lifetime retards the age‐related decline in most physiological processes in the rat and, conversely, overeating accelerates these age changes 4 .…”