HUMAN SENESCENCE: PRIMARY CAUSES AND INTERACTIONS FLOW CHART





J.D. Furber

Legendary Pharmaceuticals,
PO Box 5823,
Redwood City CA 94063-0823




The many observable signs and symptoms of human senescence have been hypothesized by various researchers to result from several primary causes. Close inspection of the biochemical pathways associated with each of the hypothesized causes of human senescence shows interactions and feedback among them. As an aid to keeping track of the many interactions, a flow chart is presented.


The mechanisms which are incorporated into the flow chart include:


-- Nonenzymatic glycation of long-lived proteins and nuclear DNA.
-- Accumulation of mutations in the mitochondrial genomes of postmitotic cells.
-- Increasing acetylation of histones opens heterochromatin, permitting inappropriate expression of aging-specific genes.
-- Accumulation of lipofuscin in lysosomes of postmitotic cells.
-- Redox stress from Reactive Oxidative Species (ROS or Free Radicals) causes both oxidative damage to macromolecules and increased redox potential. Increased redox potential alters some intracellular signaling pathways and alters some enzyme activities.
-- Damage and crosslinking to long-lived macromolecules in postmitotic cells and extracellular matrix.
-- Telomere shortening induces altered phenotype and a halt in cell division in some cells.
-- Apoptosis, necrosis, and cell loss leading to tissue wasting and organ malfunction.
-- Alterations in neuroendocrine and immune systems.
-- Decline in rate of repair and turnover of macromolecules and organelles.
-- Export of toxic reactive species and cytokines from senescent cells.
-- Induction of cancer.


This flow chart will be maintained on the Worldwide Web as a reference to researchers, and will be updated as new information comes to light.


http://www.LegendaryPharma.com/senescence.html#Mechanisms




Key words: senescence, aging, biochemistry, flowchart, causes







Problems or questions regarding this site should be directed to webmaster@americanaging.org