Timekeeping in genetically programmed aging.

Genetically programmed aging, with its cellular genetic switching implied by the in vitro Hayflick limit, requires additional timing devices to coordinate the switching processes within the different cells of a highly complex life form. Evolutionary arguments have been presented elsewhere to support the need for a centralized timing mechanism as against a localized mean-field alternative. Extensive evidence is now available for the role of the pineal gland and its secreted melatonin in the aging process. The nightly melatonin peak changes with age, thus providing a potential signal to inform all of the cells in the organism of its age. Here it is hypothesized that the decoding of this "durational signal" at the cellular level is carried out with the aid of the sleep induced pCO2 changes in the blood. To test this hypothesis, modifications of the in vitro Hayflick experiment and of the in vivo Pierpaoli longevity experiment involving rhythmic addition of melatonin and pH manipulations are proposed.