Isao Shimokawa, MD, PhD
Pathology & Gerontology,
Department of Respiratory and Digestive Medicine,
Nagasaki University School of Medicine,
Nagasaki, Japan.

Introduction
Caloric restriction (CR)--the restriction of food intake while maintaining adequate supplies of essential nutrients (i.e. not malnutrition)--is widely recognized as the most powerful intervention for the extension of lifespan in organisms. CR slows the aging process, prevents or retards age-related diseases and extends the mean and maximum lifespan in laboratory organisms.^1,2 In the 66 years since the seminal report of McCay,³ many studies have confirmed its life-extending effects. These effects do not depend on the restriction of specific nutrients or food contaminants.4 Despite numerous efforts, our knowledge of the mechanisms underlying the effects of CR is not yet complete. The present article focuses on several possible mechanisms. Other historic and recent research can be found in more comprehensive reviews^1,2 and a recent update.⁴

An Evolutionary Perspective
It has been suggested that the anti-aging effects of CR might derive from adaptive responses that evolved to maximize organism survival during periods of food shortage. In order to avoid extinction, organisms have evolved neuroendocrine and metabolic response systems to enhance survival during natural periods of food shortage.

Anna Liachenko, BSc, MSc
Managing Editor,
Geriatrics & Aging

The relationship between aging and cancer has its basis in cell cycle alterations. While multiple factors affect cell cycle progression, recent research has directed a great deal of attention to telomere length as a key factor affecting mammalian cell proliferation. This article discusses recent findings with respect to the role of telomeres and telomerase in cancer, cellular aging, and longevity.

Telomeres are short DNA repeats located at the ends of eukaryotic chromosomes. Telomeres cap chromosomal ends preventing the loss of important genes during cell division. With every cell division, the length of telomeres decreases unless it is corrected by telomerase, a ribonucleoprotein enzyme that extends the telomeres by adding hexameric nucleotide repeats to the ends of chromosomes. In humans, telomeres are short, and telomerase activity is low in many somatic tissues but is present in germ cells, activated leukocytes, and stem cells from a variety of organs. The study of telomeres has been hampered by the fact that classical animal models, such as mice, have highly active telomerase. This results in long telomeres that do not shorten enough during the animal lifespan to play a significant role in cellular aging. Recently, a genetically altered telomerase-deficient mouse model has been created by a group of researchers at Harvard.