Molecular Biology

20000922
Judith Campisi. Science Vol 289. Sciencemag.org.

Takeaway:

Calorie restriction slows down entropy in a cell lineage. CR increases SIR2p activity, which maintains heterochromatin, which protects DNA? This article may not reflect current findings, since it is 18 years old.

Ideas presented:

• In yeast, calorie restriction (CR) increased longevity requires genes NPT1 and SIR2.
• NPT1 gene encodes one of two enzymes in yeast that produce NAD.
• SIR2 gene encodes a protein that promotes a compact chromatin structure (histone deacetylase), silencing gene transcription, including at the rDNA locus.
• Accumulation of extra-chromosomal rDNA circles and DNA fragments is a major cause of yeast aging.
• Circles and fragments are excised during homologous recombination, especially from regions like the rDNA locus.
• If rDNA locus is silenced by SIR2p, then fewer circles formed.
• CR invokes higher levels of NAD, which increases SIR2p activity?
• CR reduces the impact of Mitochondrial Reactive Oxygen Species (ROS), which also increases SIR2p activity (how is not explained).
• In mammals, age related loss of silencing occurs with age, such as with the X chromosome.
• Telomere shortening occurs more rapidly on human X chromosomes, which could contribute to the age-dependent reactivation of X chromosome loci.

— Marcos Reyes 2019/04/04 12:07