Jump to content

Lipofuscin

From Wikipedia, the free encyclopedia
(Redirected fromLipochrome)
Confocal imageof a spinalmotor neuronshowing stained lipofuscin granules in blue and yellow
Micrographshowing a cluster of lipofuscin particles (arrow) in anerve cellof the brain;toluidine bluestain; scale bar = 10 microns (0.01 millimeters)

Lipofuscinis the name given to fine yellow-brownpigmentgranulescomposed oflipid-containing residues oflysosomaldigestion.[1][2]It is considered to be one of the aging or "wear-and-tear" pigments, found in theliver,kidney,heartmuscle, retina,adrenals,nervecells, andganglioncells.[3]

Formation and turnover

[edit]
Micrographshowing lipofuscin, in brown/yellow, in aliverbiopsywithground glass hepatocytes;H&E stain

Lipofuscin appears to be the product of theoxidationofunsaturated fatty acidsand may be symptomatic of membrane damage, or damage tomitochondriaandlysosomes.Aside from a large lipid content, lipofuscin is known to contain sugars and metals, includingmercury,aluminium,iron,copperandzinc.[4]Lipofuscin is also accepted as consisting of oxidized proteins (30–70%) as well as lipids (20–50%).[5]It is a type oflipochrome[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 aproteaseinhibitor (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 theleupeptin-induced material is true lipofuscin.[8][9]There exists evidence that "true lipofuscin" is not degradablein vitro;[10][11][12]whether this holdsin vivoover longer time periods is not clear.

N-retinylidene-N-retinyl-ethanolamine(A2E,a lipofuscin example)

TheABCR -/-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 cationicbis-pyridinium salt,N-retinylidene-N-retinyl-ethanolamine(A2E), which causes dry and wetage-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

[edit]
Micrographof heart muscle showing lipofuscin pigment,H&E stain

Lipofuscin accumulation in the eye, is a major risk factor implicated inmacular degeneration,a degenerative disease,[15]andStargardt disease,an inherited juvenile form of macular degeneration.

In theperipheral nervous system,abnormal accumulation of lipofuscin known aslipofuscinosis[1]is associated with a family ofneurodegenerative disorders–neuronal ceroid lipofuscinoses,the most common of these isBatten disease.

Also, pathological accumulation of lipofuscin is implicated inAlzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,certainlysosomal diseases,acromegaly,denervationatrophy,lipidmyopathy,chronic obstructive pulmonary disease,[16]andcentronuclear myopathy.Accumulation of lipofuscin in the colon is the cause of the conditionmelanosis coli.

On the other hand,myocardiallipofuscin accumulation more directly reflects chronological ageing rather than human cardiac pathology.[17]

Possible therapies

[edit]

Calorie restriction,[4]vitamin E,[4]and increasedglutathioneappear to reduce or halt the production of lipofuscin.

Thenootropic drugpiracetamappears to significantly reduce accumulation of lipofuscin in the brain tissue of rats.[18]

Other possible treatments:

Wetmacular degenerationcan be treated using selectivephotothermolysiswhere a pulsed unfocusedlaserpredominantly 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 removetattoos,liverspots,and in general make skin appear younger. This ability to selectively target lipofuscin has opened up research opportunities in the field ofanti-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 andStargardt disease,for which there is currently no treatment. The drug has now been grantedorphan drugdesignation for the treatment of Stargardt disease by the European Medicines Agency.[25]

Other uses

[edit]

Lipofuscin quantification is used for age determination in variouscrustaceanssuch aslobstersandspiny 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 orotolithsare 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.

See also

[edit]

References

[edit]
  1. ^abAlberts, Daniel Albert (2012).Dorland's illustrated medical dictionary(32nd ed.). Philadelphia, PA: Saunders/Elsevier. p. 1062.ISBN978-1-4160-6257-8.
  2. ^"Medical Definition of LIPOFUSCIN".www.merriam-webster.com.
  3. ^Young B, Lowe JS, Stevens A, Heath JW. Wheater's Functional Histology: A Text and Atlas. 6th ed. Elsevier
  4. ^abcChris Gaugler, "LipofuscinArchived2007-07-15 at theWayback Machine",Stanislaus Journal of Biochemical ReviewsMay 1997
  5. ^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.PMC11131928.PMID18278576.S2CID6833509.
  6. ^"lipochrome",The Free Dictionary,retrieved2021-02-18
  7. ^Katz, ML; Rice, LM; Gao, CL (1999)."Reversible accumulation of lipofuscin-like inclusions in the retinal pigment epithelium".Investigative Ophthalmology & Visual Science.40(1): 175–181.PMID9888441.
  8. ^Terman, Alexei; Brunk, Ulf T. (1999)."Is Lipofuscin Eliminated from Cells?".Investigative Ophthalmology and Visual Science.40(10): 2463–2464.PMID10476822.
  9. ^Davies, Sallyanne; Ellis, Steven (1999)."Lipofuscin Turnover".Investigative Ophthalmology and Visual Science.40(8): 1887–1888.PMID10393067.
  10. ^Terman, A, Brunk, UT (1998). "On the degradability and exocytosis of ceroid/lipofuscin in cultured rat cardiac myocytes".Mech Ageing Dev.100(2): 145–156.doi:10.1016/S0047-6374(97)00129-2.PMID9541135.S2CID34448638.{{cite journal}}:CS1 maint: multiple names: authors list (link)
  11. ^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.S2CID44822239.
  12. ^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.
  13. ^Weng J, Mata NL, Azarian SM, Tzekov RT, Birch DG, Travis GH (July 1999)."Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice".Cell.98(1): 13–23.doi:10.1016/S0092-8674(00)80602-9.PMID10412977.S2CID18605680.
  14. ^Maeda A, Maeda T, Golczak M, Palczewski K (September 2008)."Retinopathy in mice induced by disrupted all-trans-retinal clearance".The Journal of Biological Chemistry.283(39): 26684–93.doi:10.1074/jbc.M804505200.PMC2546559.PMID18658157.
  15. ^John Lacey, "Harvard Medical signs agreement with Merck to develop potential therapy for macular degeneration",23-May-2006
  16. ^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.
  17. ^Kakimoto, Yu; Okada, Chisa; Kawabe, Noboru; Sasaki, Ayumi; Tsukamoto, Hideo; Nagao, Ryoko; Osawa, Motoki (2019)."Myocardial lipofuscin accumulation in ageing and sudden cardiac death".Scientific Reports.9(1): 3304.Bibcode:2019NatSR...9.3304K.doi:10.1038/s41598-019-40250-0.ISSN2045-2322.PMC6397159.PMID30824797.
  18. ^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.
  19. ^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.S2CID29129359.
  20. ^Amenta F, Ferrante F,et al.,Reduced lipofuscin accumulation in senescent rat brain by long-term acetyl-L-carnitine treatment.Arch Gerontol Geriatr.1989 Sep-Oct;9(2):147-53.
  21. ^Huang, SZ; Luo, YJ; Wang, L; Cai, KY (Jan 2005)."Effect of ginkgo biloba extract on livers in aged rats".World J Gastroenterol.11(1): 132–5.doi:10.3748/wjg.v11.i1.132.PMC4205372.PMID15609412.
  22. ^Stenbäck, Frej; Weisburger, J. H.; Williams, G. M. (1988-02-01)."Effect of lifetime, administration of dimethylaminoethanol on longevity, aging changes, and cryptogenic neoplasms in C3H mice".Mechanisms of Ageing and Development.42(2): 129–138.doi:10.1016/0047-6374(88)90068-1.ISSN0047-6374.PMID3361965.S2CID45595812.
  23. ^Shen, Li-Rong; Parnell, Laurence D.; Ordovas, Jose M.; Lai, Chao-Qiang (January 2013)."Curcumin and aging".BioFactors.39(1): 133–140.doi:10.1002/biof.1086.ISSN1872-8081.PMID23325575.S2CID39360837.
  24. ^Julien, S; Schraermeyer, U (Oct 2012). "Lipofuscin can be removed from the retinal pigment epithelium of monkeys".Neurobiol Aging.33(10): 2390–7.doi:10.1016/j.neurobiolaging.2011.12.009.PMID22244091.S2CID22829613.
  25. ^"EU/3/13/1208".17 September 2018.Retrieved1 June2021.
  26. ^Ingebrigt Uglem, Mark Belchier & Terje Svåsand (2005)."Age determination of European lobsters (Homarus gammarusL.) by histological quantification of lipofuscin ".Journal of Crustacean Biology.25(1): 95–99.doi:10.1651/c-2448.JSTOR1549930.
  27. ^Kerry E. Maxwell; Thomas R. Matthews; Matt R. J. Sheehy; Rodney D. Bertelsen; Charles D. Derby (2007)."Neurolipofuscin is a measure of age inPanulirus argus,the Caribbean spiny lobster, in Florida ".The Biological Bulletin.213(1): 55–66.doi:10.2307/25066618.JSTOR25066618.PMID17679720.S2CID8522101.

20. Young B, Lowe JS, Stevens A, Heath JW. Wheater's Functional Histology: A Text and Atlas. 6th ed. Elsevier

[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Lipofuscin&oldid=1227031539"