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jtitle_s:("Age (dodr)")
1.  Aging of the striatum: mechanisms and interventions 
Age  2008;30(4):251-261.
Motor function declines with increasing adult age. Proper regulation of the balance between dopamine (DA) and acetylcholine (ACh) in the striatum has been shown to be fundamentally important for motor control. Although other factors can also contribute to this age-associated decline, a decrease in the concentration and binding potential of the DA D2 receptor subtype in the striatum, especially in the cholinergic interneurons, are involved in the mechanism. Our studies have shown that gene transfer of the DA D2 receptor subtype with adenoiviral vectors is effective in ameliorating age-associated functional decline of the striatal cholinergic interneurons. These achievements confirm that an age-associated decrease of D2R contributes functional alteration of the interaction of DA and ACh in the striatum and demonstrate that these age-associated changes indeed are modifiable.
PMCID: PMC2585651  PMID: 19424849
Dopamine receptor D2; Viral vector; Acetylcholine; Interneuron
2.  Effects of calorie restriction on chromosomal stability in rhesus monkeys (Macaca mulatta) 
Age  2006;29(1):15-28.
The basic tenet of several theories on aging is increasing genomic instability resulting from interactions with the environment. Chromosomal aberrations have been used as classic examples of increasing genomic instability since they demonstrate an increase in numerical and structural abnormalities with age in many species including humans. This accumulating damage may augment many aging processes and initiate age-related diseases, such as neoplasias. Calorie restriction (CR) is one of the most robust interventions for reducing the frequency of age-related diseases and for extending life span in many short-lived organisms. However, the mechanisms for the anti-aging effects of CR are not yet well understood. A study of rhesus monkeys was begun in 1987 to determine if CR is also effective in reducing the frequency of age-related diseases and retarding aging in a long-lived mammal. Male monkeys were begun on the diet in 1987, and females were added in 1992 to examine a possible difference in response to CR by sex. The CR monkeys have been maintained for over 10 years on a low-fat nutritional diet that provides a 30% calorie reduction compared to a control (CON) group. Because of the greater similarity of nonhuman primates to humans in life span and environmental responses to diet compared with those of rodents, the rhesus monkey provides an excellent model for the effects of CR in humans. This study examined the effects of CR on chromosomal instability with aging. Significant age effects were found in both CR and CON groups for the number of cells with aneuploidy: old animals had a higher loss and a higher gain than young animals. However, there was no effect of age on chromosomal breakage or structural aberrations in either diet group. Diet had only one significant effect: the CR group had a higher frequency of chromatid gaps than did the CON group. CR, implemented in adult rhesus monkeys, does not have a major effect on the reduction of numerical or structural aberrations related to aging.
PMCID: PMC2267682  PMID: 19424827
aging; calorie restriction; chromosomal stability; diet; rhesus monkeys
3.  Caloric restriction versus drug therapy to delay the onset of aging diseases and extend life 
Age  2005;27(1):39-48.
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.
PMCID: PMC3456093  PMID: 23598602
blood pressure; calorie restriction mimetics; cardiovascular disease; cholesterol; lifespan; medications

Results 1-3 (3)