title: The Lag of the Proliferative Aging Clock Underlies the Lifespan-Extending Effect of Calorie Restriction.
abstract: BACKGROUND
  The nature of the life-extending effect of calorie restriction (CR) is an unsolved problem in biology since 30 years of the last century. Furthermore, many different factors that cause analogous life-extending effect, so called CR-mimetic factors, have been found. They increase the lifespan of different animal species (repeatedly in invertebrates) and therefore remain in the forefront of anti-aging researches. The aims of this paper is to find an overarching solution for the nature of CR and all CR-mimetic factors and to analyze the consequences following this phenomenon.
  
  
  METHODS
  The analysis of empirical scientific data, which concern aging process and boundary areas from the point of view of the bioenergetics theory of aging.
  
  
  RESULTS
  "Anything that affects a living system that slows (accelerates) the rate of cell division entails extending (reducing) life duration" is this overarching solution. CR is one of such factors that cause a retardation in the rate of cell divisions due to the shortage in 'construction materials' necessary for doubling cell mass during reduplication. This put a brake on realization of the aging program. To draw this conclusion, a new concept of the proliferative aging clock based on bioenergetics theory of aging was put forward. This clock governs the rate of the aging process via programmed, proliferative dependent and stepwise bioenergetics decline.
  
  
  CONCLUSIONS
  The mechanism of the life-extending effect of CR and CR-mimetic factors is not related to that of natural aging, therefore this unable to be the basis for elaboration of radical remedy for senescence. However, both the CR and some of CR-mimetic factors can undoubtedly lead to human life extension: our organism differs from that of the other mammals only slightly. It is the wellbeing and vulnerability of such extended life that are under consideration. To achieve a healthy and unlimited life it is necessary to reprogram gene expression so that cell bioenergetics levels either remain at a previous level after cell division, which will stop aging, or else grow, which will result in organism rejuvenation.
authors.affiliation: Institute of Biology and Soil Sciences of Far Eastern Branch of Russian Academy of Sciences, pr. 100- letiya Vladivostoka 159, Vladivostok, 690022, Russia. trubitsyn35@mail.ru.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Trubitsyn
mesh_terms: D000375:Aging; D000818:Animals; D031204:Caloric Restriction; D049109:Cell Proliferation; D004734:Energy Metabolism; D006801:Humans; D008017:Life Expectancy