Lipofuscin appears to be the product of the
oxidation of
unsaturated fatty acids and may be symptomatic of membrane damage, or damage to
mitochondria and
lysosomes. Aside from a large lipid content, lipofuscin is known to contain sugars and metals, including
mercury,
aluminium,
iron,
copper and
zinc.[4] Lipofuscin is also accepted as consisting of oxidized proteins (30–70%) as well as lipids (20–50%).[5] It is a type of
lipochrome[6] and is specifically arranged around the nucleus.
The accumulation of lipofuscin-like material may be the result of an imbalance between formation and disposal mechanisms. Such accumulation can be induced in rats by administering a
protease inhibitor (
leupeptin); after a period of three months, the levels of the lipofuscin-like material return to normal, indicating the action of a significant disposal mechanism.[7] However, this result is controversial, as it is questionable if the
leupeptin-induced material is true lipofuscin.[8][9] There exists evidence that "true lipofuscin" is not degradable in vitro;[10][11][12] whether this holds in vivo over longer time periods is not clear.
The ABCR -/- knockout mouse has delayed dark adaptation but normal final rod threshold relative to controls.[13] Bleaching the retina with strong light leads to formation of toxic cationic bis-pyridinium salt, N-retinylidene-N-retinyl-ethanolamine (A2E), which causes dry and wet
age-related macular degeneration.[14] From this experiment, it was concluded that ABCR has a significant role in preventing formation of A2E in extracellular photoreceptor surfaces during bleach recovery.
Relation to diseases
Lipofuscin accumulation in the eye, is a major risk factor implicated in
macular degeneration, a degenerative disease,[15] and
Stargardt disease, an inherited juvenile form of macular degeneration.
Wet
macular degeneration can be treated using selective
photothermolysis where a pulsed unfocused
laser predominantly heats and kills lipofuscin-rich cells, leaving untouched healthy cells to multiply and fill in the gaps.[citation needed] The technique is also used as a skin treatment to remove
tattoos,
liverspots, and in general make skin appear younger. This ability to selectively target lipofuscin has opened up research opportunities in the field of
anti-aging medicine.
Soraprazan (remofuscin) has been found to remove lipofuscin from retinal pigment epithelial cells in animals.[24] This opens up a new therapy option for the treatment of dry age-related macular degeneration and
Stargardt disease, for which there is currently no treatment. The drug has now been granted
orphan drug designation for the treatment of Stargardt disease by the European Medicines Agency.[25]
Other uses
Lipofuscin quantification is used for age determination in various
crustaceans such as
lobsters and
spiny lobsters.[26][27] Since these animals lack bony parts, they cannot be aged in the same way as bony fish, in which annual increments in the ear-bones or
otoliths are commonly used. Age determination of fish and shellfish is a fundamental step in generating basic biological data such as growth curves, and is needed for many stock assessment methods. Several studies have indicated that quantifying the amount of lipofuscin present in the eye-stalks of various crustaceans can give an index of their age. This method has not yet been widely applied in fisheries management mainly due to problems in relating lipofuscin levels in wild-caught animals with accumulation curves derived from aquarium-reared animals.
^
abAlberts, Daniel Albert (2012). Dorland's illustrated medical dictionary (32nd ed.). Philadelphia, PA: Saunders/Elsevier. p. 1062.
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^Double, KL; Dedov, VN; Fedorow, H; Kettle, E; Halliday, GM; Garner, B; Brunk, UT (June 2008). "The comparative biology of neuromelanin and lipofuscin in the human brain". Cellular and Molecular Life Sciences. 65 (11): 1669–82.
doi:
10.1007/s00018-008-7581-9.
PMID18278576.
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^"lipochrome", The Free Dictionary, retrieved 2021-02-18
^Terman, A; Brunk, UT (1998). "Ceroid/lipofuscin formation in cultured human fibroblasts: the role of oxidative stress and lysosomal proteolysis". Mech Ageing Dev. 104 (3): 277–291.
doi:
10.1016/s0047-6374(98)00073-6.
PMID9818731.
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^Elleder, M; Drahota, Z; Lisá, V; Mares, V; Mandys, V; Müller, J; Palmer, DN (1995). "Tissue culture loading test with storage granules from animal models of neuronal ceroid-lipofuscinosis (Batten disease): testing their lysosomal degradability by normal and Batten cells". Am J Med Genet. 57 (2): 213–221.
doi:
10.1002/ajmg.1320570220.
PMID7668332.
^Joakim Allaire; François Maltais; Pierre LeBlanc; Pierre-Michel Simard; François Whittom; Jean-François Doyon; Clermont Simard; Jean Jobin (2002). "Lipofuscin accumulation in the vastus lateralis muscle in patients with chronic obstructive pulmonary disease". Muscle and Nerve. 25 (3): 383–389.
doi:
10.1002/mus.10039.
PMID11870715.
S2CID22309073.
^Paula-Barbosa, M.; et al. (1991). "The effects of Piracetam on lipofuscin of the rat cerebellar and hippocampa; neurons after long-term alcohol treatment and withdrawal". Alcoholism: Clinical and Experimental Research. 15 (5): 834–838.
doi:
10.1111/j.1530-0277.1991.tb00610.x.
PMID1755517.
^Roy, D; Pathak, DN; Singh, R (1983). "Effect of centrophenoxine on the antioxidative enzymes in various regions of the aging rat brain". Exp Gerontol. 18 (3): 185–97.
doi:
10.1016/0531-5565(83)90031-1.
PMID6416880.
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