• Fernandes, Gabriel (PI)
  • Nelson, James F (PI)
  • Richardson, Arlan (PI)
  • Ward, Walter F. (PI)
  • Depaolo, Louie V. (PI)
  • Herlihy, Jeremiah T. (PI)
  • McCarter, Roger J. (PI)
  • Masoro, Edward J. (PI)
  • Mc Carter, Roger (PI)
  • Yu, Byung (PI)
  • Kalu, Dike (PI)
  • Bertrand, Helen (PI)
  • McCarter, Roger (PI)
  • Richardson, Arlan G. (PI)
  • Ward, Walter Frederick (PI)
  • Richardson, Arlan G (PI)

Project: Research project

Project Details


The primary aim of this proposal is to investigate the cellular and
molecular mechanisms underlying the remarkable anti-aging action of
dietary restriction. Intensive research endeavors from the past two
decades have firmly established that dietary restriction is the most
efficacious, and in fact the only, means available to gerontologists of
intervening in the aging processes in mammals. Therefore, we propose
that the mechanistic delineation of the action of dietary restriction is
the most logical approach leading to a better understanding and probing
of the complex biological aging processes. The central theme of the proposed project is built on the concept that
aging processes involve the loss in the ability of organisms to maintain
cellular homeostasis due to deterioration of self-regulatory mechanisms
at various levels. Therefore, it is our hypothesis that dietary
restriction exerts its anti-aging action by maintaining in optimal
condition the integrative and self regulatory capacities of critical
intracellular and extracellular biochemical processes. Project I tests the hypothesis that the modulation of free radical
activity and attenuation of the resulting oxidative alterations are
mechanisms by which dietary restriction retards aging and its disease
processes. Project II explores the cellular mechanisms by which dietary
restriction enhances the efficiency of DNA repair in specific genes.
Project IV examines the proteolytic processes which degrade abnormal and
altered proteins and their modulation by dietary restriction. Project VI
explores the age-related alterations in cellular calcium regulation and
the mechanisms by which dietary restriction maintains calcium
homeostasis. Project VII tests the hypothesis that dietary restriction
retards aging processes by modifying the cellular characteristics of
fuel utilization. Project VIII investigates the mechanism underlying
mild hyperadrenocorticism associated with dietary restriction and tests
the hypothesis that the hyperadrenocorticism potentiates cellular
homeostasis and contributes to its life-prolonging action. These studies
will permit a broader understanding and knowledge of the molecular and
cellular mechanisms responsible for te anti-aging action of dietary
restriction and provide new insights into the mechanisms underlying the
biological aging processes.
Effective start/end date6/1/795/31/99


  • National Institutes of Health


  • Medicine(all)


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