Hypothesis: lifespan is regulated by chronomere DNA of the hypothalamus.
As the basis for the lifelong clock and as a primary cause of aging, a process of shortening of hypothetical perichromosomal DNA structures termed chronomeres is proposed in the CNS. The lifelong clock is regulated by the shortening of chronomere DNA in postmitotic neurons of the hypothalamus. Shortening of these DNA sequences occurs in humans on a monthly basis through a lunasensory system and is controlled by release of growth hormone discharged from the anterior pituitary directly into the hypothalamus via local blood vessels. In adults, this process is under control of the pineal gland. It is further proposed that different forms of Alzheimer's disease (AD) are caused by somatic and inherited deletions of chronomeres followed by a further abnormally accelerated decrease in their activity, resulting in failures of neurotrophic and neuroendocrinal activities and in various cellular imbalances. In this model, AD is considered as a segmental progeria caused by shortening of anomalous chronomeres that are partially deleted in early development. It is proposed that a calorie-restricted diet retards chronomere shortening due to a local deficit of growth hormone in the surroundings of hypothalamic cells, thus slowing the lifelong clock and delaying aging. Calorie restriction increases lifespan by preserving mitochondrial and other organismal functions owing to the decreased chronomere shortening.
Olovnikov
A M
AM
Institute of Biochemical Physics, Russian Academy of Sciences, Chernyakhovskogo, 5-94, Moscow, 125319 Russia. olovnikov@dol.ru
D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics; D000818:Animals; D001683:Biological Clocks; D005075:Biological Evolution; D002872:Chromosome Deletion; D003599:Cytoskeleton / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005609:Free Radicals / Q000378:metabolism; D006112:Gravitation; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000502:physiology; D008136:Longevity / Q000235:genetics*; D016081:Moon; D010870:Pineal Gland / Q000503:physiopathology; D010902:Pituitary Gland / Q000503:physiopathology; D016615:Telomere / Q000502:physiology*; D014898:Werner Syndrome / Q000235:genetics
D005609:Free Radicals; D004247:DNA