The Effect of Retardation of Growth Upon the Breeding Period and Duration of Life of Rats

Osborne, Thomas B.; Mendel, Lafayette B.; Ferry, Edna L.

doi:10.1126/science.45.1160.294

Cited by 169 publications

(93 citation statements)

References 3 publications

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“…In one study, C3H mice that were given Tempol in their drinking water at a concentration of 58mM maintained a normal healthy weight while sucrosefed controls gained substantial weight very quickly ( Figure 13) [56]. Caloric restriction is know to increase lifespan in mice [97][98][99]. In a long term study, Tempol treated mice had a significantly increased survival, 123 vs. 92.6 weeks, and remained more active as they aged [56].…”

Section: Weight Controlmentioning

confidence: 99%

The chemistry and biology of nitroxide compounds

Soule

Hyodo

Matsumoto

et al. 2007

Free Radical Biology and Medicine

467

387

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Cyclic nitroxides are a diverse range of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15-20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described including their ability to degrade superoxide and peroxide, inhibit Fenton reactions and undergo radical-radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. While much remains to be done, many applications have been well studied and some are presently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials.

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Section: Weight Controlmentioning

confidence: 99%

The chemistry and biology of nitroxide compounds

Soule

Hyodo

Matsumoto

et al. 2007

Free Radical Biology and Medicine

467

387

View full text Add to dashboard Cite

show abstract

“…Since the findings of Osborne et al (6) , a huge body of work has examined DR across many species, primarily in the quest to unravel the mechanisms driving the ageing process. This research clearly demonstrates that DR is the most reproducible environmental intervention through which median and maximum lifespan can be extended (11)(12)(13)(14)(15)(16) .…”

Section: The Universality Of Dietary Restriction On Lifespan and Healmentioning

confidence: 99%

“…protein, carbohydrate and amino acids) are restricted without any reduction in energy intake per se (1)(2)(3)(4) . While the periods of fasting undertaken by religious ascetics have been known for centuries to increase awareness and activity (5) , the first experimental evidence that a restricted diet could impact positively on lifespan was provided by Osborne et al almost 100 years ago (6) . These authors reported that DR caused stunting of female rats, resulting in extended lifespan and a longer reproductive period, relative to non-stunted controls.…”

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confidence: 99%

Dietary restriction and the pursuit of effective mimetics

Selman

2014

Proc. Nutr. Soc.

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Dietary restriction (DR) has been shown to extend both median and maximum lifespan in a range of animals, although recent findings suggest that these effects are not universally enjoyed across all animals. In particular, the lifespan effect following DR in mice is highly strain-specific and there is little current evidence that DR induces a positive effect on all-cause mortality in non-human primates. However, the positive effects of DR on health appear to be highly conserved across the vast majority of species, including human subjects. Despite these effects on health, it is highly unlikely that DR will become a realistic or popular life choice for most human subjects given the level of restraint required. Consequently significant research is focusing on identifying compounds that will bestow the benefits of DR without the obligation to adhere to stringent reductions in daily food intake. Several such compounds, including rapamycin, metformin and resveratrol, have been identified as potential DR mimetics. Although these compounds show significant promise, there is a need to properly understand the mechanisms through which these drugs act. This review will discuss the importance in understanding the role that genetic background and heterogeneity play in mediating the lifespan and healthspan effects of DR. It will also provide an overview of the most promising current DR mimetics and their effects on healthy lifespan.

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“…In the early 1900s, several scientists reported that decreasing food intake by female rats delayed the onset of fertility and extended their life span (McCay 1933;Osborne et al 1917). Since then, several studies demonstrated that a caloric reduction of 30% was sufficient to achieve life extension in rodent models.…”

Section: Caloric Restrictionmentioning

confidence: 99%

Improving immunity in the elderly: current and future lessons from nonhuman primate models

Meyer

Kerns

Haberthur

et al. 2011

AGE

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The immune system must overcome daily challenges from pathogens to protect the body from infection. The success of the immune response to infection relies on the ability to sense and evaluate microbial threats and organize their elimination, while limiting damage to host tissues. This delicate balance is achieved through coordinated action of the innate and adaptive arms of the immune system. Aging results in several structural and functional changes in the immune system, often described under the umbrella term "immune senescence". Age-related changes affect both the innate and adaptive arms of the immune system and are believed to result in increased susceptibility and severity of infectious diseases, which is further exacerbated by reduced vaccine efficacy in the elderly. Therefore, multiple strategies to improve immune function in the aged are being investigated. Traditionally, studies on immune senescence are conducted using inbred specific pathogen free (SPF) rodents. This animal model has provided invaluable insight into the mechanisms of aging. However, the limited genetic heterogeneity and the SPF status of this model restrict the successful transfer of immunological discoveries between murine models and the clinical setting. More recently, nonhuman primates (NHPs) have emerged as a leading translational model to investigate immune senescence and to test interventions aimed at delaying/reversing agerelated changes in immune function. In this article, we review and summarize advances in immunorestorative approaches investigated in the NHP model system and discuss where the NHP model can support the development of novel therapeutics.

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The Effect of Retardation of Growth Upon the Breeding Period and Duration of Life of Rats

Cited by 169 publications

References 3 publications

The chemistry and biology of nitroxide compounds

The chemistry and biology of nitroxide compounds

Dietary restriction and the pursuit of effective mimetics

Improving immunity in the elderly: current and future lessons from nonhuman primate models

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