Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction

  title={Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction},
  author={Stephen Richard Spindler},
  journal={Mechanisms of Ageing and Development},
  • S. Spindler
  • Published 1 September 2005
  • Biology
  • Mechanisms of Ageing and Development

Conserved and tissue-specific genic and physiologic responses to caloric restriction and altered IGFI signaling in mitotic and postmitotic tissues.

It is argued that the longevity effects of CR are derived from repeated cycles of apoptosis and autophagic cell death in mitotically competent tissues and protein turnover and cellular repair in postmitotic tissues.

Use of microarray biomarkers to identify longevity therapeutics

Test the hypothesis that existing pharmaceuticals can mimic the physiologic effects of CR by evaluating the effectiveness of glucoregulatory drugs and putative cancer chemopreventatives in reproducing the hepatic gene‐expression profiles produced by long‐term CR (LTCR), and find that metformin treatment was superior to 8 weeks of CR at reproduces the specific changes in transcript levels produced by LTCR.

Adult-onset, short-term dietary restriction reduces cell senescence in mice

The data suggest the possibility that reduction of cell senescence may be a primary consequence of DR which in turn may explain known effects of DR such as improved mitochondrial function and reduced production of reactive oxygen species.

Identification of potential caloric restriction mimetics by microarray profiling.

Results indicate that gene expression biomarkers can be used to identify promising candidate CR mimetics, and metformin has been shown to reduce cancer incidence in mice and humans.

Beneficial Biochemical Outcomes of Late‐Onset Dietary Restriction in Rodents

Dietary restriction or caloric restriction initiated late in life in rodent models suggests a possibility that DR/CR is beneficial if applied in middle‐aged or early senescent obese people, however, it is argued that application of late life DR/ CR can be harmful if practiced in people who are already eating modestly.

Oxidative Stress, Dietary Restriction and Aging

This observation does not support the interpretation that the extended survival induced by DR feeding results from a slower life time rate of accrual of oxidative damage, and the use of a small molecular mimetic of the DR effect may provide an alternative experimental approach to identify the mechanism underlying the extended Survival observed.

Dietary restriction in Drosophila melanogaster

Dietary Restriction (DR), the reduction of nutrient intake without malnutrition, was first shown to extend lifespan in rodents in 1935. DR has subsequently proven to be a 'public' method of

Caloric restriction: From soup to nuts

  • S. Spindler
  • Biology, Medicine
    Ageing Research Reviews
  • 2010

Transcription‐blocking DNA damage in aging: a mechanism for hormesis

  • B. Schumacher
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2009
A mechanistic basis for hormesis is discussed and its implications for cancer prevention and healthy aging are discussed.

Nutritional limitation in early postnatal life and its effect on aging and longevity in rodents




Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice

Genome-wide microarray expression analysis of 11,000 genes in an aging potentially mitotic tissue, the liver, shows that the early changes in gene expression, which extend into old age, are key to the life- and health-span-extending effects of CR.

Temporal linkage between the phenotypic and genomic responses to caloric restriction.

It is demonstrated that CR initiated in 19-month-old mice begins within 2 months to increase the mean time to death by 42% and increase mean and maximum lifespans by 4.7 and 6.0 months, respectively, which suggest a cause-and-effect relationship between the rate of aging and the CR-associated gene expression biomarkers.

Dietary Restriction Initiated in Late Adulthood Can Reverse Age‐related Alterations of Protein and Protein Metabolism

It is conceivable that DR conducted in old age can be beneficial not only to retard age‐related functional decline but also to restore functional activity in young rodents.

Reversible effects of long-term caloric restriction on protein oxidative damage.

Overall, the current findings indicate that changes in the level of caloric intake may reversibly affect the concentration of oxidized proteins and sufhydryl content and also retards the age-associated accumulation of oxidative damage.

Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans.

This review synthesizes the key biological mechanisms underlying many of the beneficial effects of CR, with a particular focus on the insulin-like growth factor-1 pathway and some of the opportunities now available for investigations.

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

Evidence is provided that aging of the heart is associated with specific transcriptional alterations, and that CR initiated in middle age may retard heart aging by inducing a profound transcriptional reprogramming.

Genotype and age influence the effect of caloric intake on mortality in mice

Results of this study indicate that CR does not have beneficial effects in all strains of mice, and it increases rather than decreases mortality if initiated in advanced age.

Molecular mechanisms linking calorie restriction and longevity.

  • B. Merry
  • Biology
    The international journal of biochemistry & cell biology
  • 2002

Demography of Dietary Restriction and Death in Drosophila

Dietary restriction in Drosophila extends life-span entirely by reducing the short-term risk of death, and two days after the application of DR at any age for the first time, previously fully fed flies are no more likely to die.

Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence.

The food intake of 12- to 13-month-old mice of two long-lived strains was restricted by using nutrient-enriched diets in accordance with the concept of "undernutrition without malnutrition" and spontaneous lymphoma was inhibited.