Evolutionary Medicine: From Dwarf Model Systems to Healthy Centenarians?

  title={Evolutionary Medicine: From Dwarf Model Systems to Healthy Centenarians?},
  author={Valter D. Longo and Caleb E. Finch},
  pages={1342 - 1346}
Restriction of the number of calories consumed extends longevity in many organisms. In rodents, caloric restriction decreases the levels of plasma glucose and insulin-like growth factor I (IGF-1) and postpones or attenuates cancer, immunosenescence, and inflammation without irreversible side effects. In organisms ranging from yeast to mice, mutations in glucose or IGF-I–like signaling pathways extend life-span but also cause glycogen or fat accumulation and dwarfism. This information suggests a… 

Aging and survival: the genetics of life span extension by dietary restriction.

How recent work in nonmammalian model organisms has revealed new insight into the genetics of DR and how the discovery of DR-specific transcription factors will advance the understanding of this phenomenon are discussed.

Aging and Dietary Restriction: The Yeast Paradigm

Some of the methods and discoveries related to dietary restriction (DR) and aging in yeast are reviewed and the potential genes and mechanisms mediated its effect on life span are discussed.

Longevity genes: from primitive organisms to humans

  • H. Warner
  • Medicine
    Mechanisms of Ageing and Development
  • 2005

Murine models of life span extension.

Targeted mutations that affect components of this pathway, including the GH receptor, p66Shc, and the IGF-1 receptor (IGF-1R), also extend life span, and these effects on life span may result from an increased capacity to resist oxidative damage.

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

The somatotropic axis and aging: Benefits of endocrine defects.

  • A. BartkeE. ListJ. Kopchick
  • Biology, Medicine
    Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society
  • 2016

Genes against aging.

  • Richard A. Miller
  • Biology
    The journals of gerontology. Series A, Biological sciences and medical sciences
  • 2012
This essay compares different strategies for using genetic information to clarify questions in biogerontology, suggesting an emphasis on genes that can retard multiple forms of age-dependent dysfunction in parallel.

Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction

The present findings support the notion that enhanced sensitivity to insulin plays a prominent role in the actions of CR and GH resistance on longevity and imply that somatotropic signaling is critically important not only in the control of aging and longevity under conditions of unlimited food supply but also in mediating the effects of CR on life span.

Calorie restriction: Decelerating mTOR-driven aging from cells to organisms (including humans)

It is discussed that the anti-aging effect of CR rules out accumulation of DNA damage and failure of maintenance as a cause of aging, and suggests that aging is driven in part by the nutrient-sensing TOR network, thus slowing aging and delaying diseases of aging.

Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice

Deletion of DGAT1 in mice provides a model of leanness and extended lifespan that is independent of calorie restriction, and is linked to metabolic conditions that favor longevity.



Longevity, Genes, and Aging

Because of its complexity, the aging process takes us into the realm of integrative biology, and thus, biogerontology should prove instrumental in deciphering the functional and regulatory circuitry of the sequenced genome.

Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production

It is shown that mice homozygous for loss-of-function mutations at the Pit1 (Snell dwarf) locus show a >40% increase in mean and maximal longevity on the relatively long-lived (C3H/HeJ × DW/J)F1 background, demonstrating that a single gene can control maximum lifespan and the timing of both cellular and extracellular senescence in a mammal.

Longevity: Extending the lifespan of long-lived mice

It is shown that calorie restriction confers a further lifespan increase in the dwarfs, indicating that the two factors may act through different pathways.

Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae.

These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD, the oxidized form of nicotinamide adenine dinucleotide.

Visions & Reflections¶Regulation of longevity and stress resistance: a molecular strategy conserved from yeast to humans?

Although the authors are only beginning to understand the molecular mechanisms that mediate life span extension, the similarities between longevity regulatory pathways in organisms ranging from yeast to mice suggest that insulin/ IGF-1 signaling pathways may also regulate cell damage and longevity in humans.

Caloric Restriction in Primates and Relevance to Humans

Results strongly suggest that the same beneficial “antiaging” and/or “antidisease” effects observed in CR rodents also occur in primates and suggest that CR primates will be less likely to incur diabetes, cardiovascular problems, and other age‐related diseases and may in fact be aging more slowly than fully fed counterparts.

Timing Requirements for Insulin/IGF-1 Signaling in C. elegans

It is found that life-span regulation can be dissociated temporally from phenotypes that might seem to decrease the quality of life, and this finds that in Caenorhabditis elegans, the pathway acts during adulthood to influence aging.

Longevity, senescence, and the genome

By comparing species that have different developmental and life spans, Finch proposes a typology of senescence from rapid to gradual to negligible, and he provides the first multiphyletic calculations of mortality rate constants.

Oxidative Stress, Caloric Restriction, and Aging

Support for this hypothesis includes the following observations: (i) Overexpression of antioxidative enzymes retards the age-related accrual of oxidative damage and extends the maximum life-span of transgenic Drosophila melanogaster and (ii) Variations in longevity among different species inversely correlate with the rates of mitochondrial generation of the superoxide anion radical and hydrogen peroxide.