Nanomedicine, Volume IIA: Biocompatibility
© 2003 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003
126.96.36.199 Intracellular Lipofuscin and Storage Diseases
Insoluble age-pigment lysosomal granules called “lipofuscin” collect in many of our cells, the accumulation starting as early in life as 11 years old and rising with age , activity level [4535, 4536] and caloric intake ; and varying with cell type [5469, 5470]. Clumps of these yellow-brown autofluorescent granules – typically 1-3 microns in diameter [4538-4540] – may occupy up to 10% of the volume of heart muscle cells , and from 20% of brainstem neuron volume at age 20 to as much as 50% of cell volume by age 90 . Lipofuscin concentrations as high as 75% have been reported in Purkinje neurons of rats subjected to protein malnutrition . Elevated concentrations in heart cells appear not to increase the risk of heart attack [4541, 4544], nor to accelerate cellular aging processes in heart muscle or liver tissues . Brain cell lipofuscin is not associated with mental [4542, 4545] or motor  abnormalities or other detrimental cellular function . Hereditary ceroid lipofuscinosis  or neuronal ceroid-lipofuscinosis (NCL) diseases  can lead to premature death, though ceroid appears to be pathological only in neurons  or when loaded into human fibroblasts . There is also considerable evidence that A2E, a hydrophobic fluorophore component  of retinal pigment epithelial lipofuscin , may contribute to age-related macular degeneration [6020-6026]. But the fact that lipofuscin is an indigestible lipid peroxidation product that cannot be excreted but whose presence appears commonly not directly injurious to the cell argues strongly that cells can tolerate significant volumetric replacements of cytoplasmic fluid with artificial foreign bodies such as medical nanorobots while continuing to function normally.
Other inert intracellular pigments are known , along with a number of pathological intracellular storage diseases [4550-4554, 5476-5478] including Fabrey’s, Gaucher’s, mannosidosis, Niemann-Pick , and Tay-Sachs, Lewy bodies in Hallervorden-Spatz disease [5919-5921], and Hirano bodies . Accumulation of lysosomal deposits of oxidized low-density lipoproteins in macrophage foam cells may contribute to atherosclerosis . Intracellular crystalloid bodies have been observed in the skeletal muscle cells of patients with hypothyroid myopathy . Noninert amyloid deposits average ~12% of pancreatic islet cell volume in patients with maturity onset diabetes .
Last updated on 30 April 2004