Lipofuscin is the name given to fine yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion and considered to be one of the aging or “wear-and-tear” pigments

August 20, 2022
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Confocal image of a spinal motor neuron showing stained lipofuscin granules in blue and yellow.
David L McIlwain, Victoria B Hoke – McIlwain DL, Hoke VB. The role of the cytoskeleton in cell body enlargement, increased nuclear eccentricity and chromatolysis in axotomized spinal motor neurons. BMC Neurosci. 6, 1, 19. 2005. doi:10.1186/1471-2202-6-19. PMID 15774011. Retention of Nissl bodies and lipfuscin by extracted motor neurons. Confocal image of an extracted motor neuron cell body isolated from human lumbar spinal cord and stained with methylene blue. The pink structures (small arrows) are Nissl bodies and the blue and yellow structures are lipofuscin granules (large arrow). Bar = 25 μm.

Lipofuscin is the name given to fine yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion.[1][2] It is considered to be one of the aging or “wear-and-tear” pigments, found in the liver, kidney, heart muscle, retina, adrenals, nerve cells, and ganglion cells.[3]

Formation and turnover

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.

Micrograph showing a cluster of lipofuscin particles (arrow) in a nerve cell of the brain; toluidine blue stain; scale bar = 10 microns (0.01 millimeters). This is a photograph of a brain nerve cell (neuron) taken with a microscope using a 100X oil-immersion objective. The arrow indicates a cluster of lipofuscin particles in the cytoplasm. The tissue was embedded in plastic, cut at a thickness of 2 microns, and stained with the dye toluidine blue. The bar at the lower right indicates a distance of 10 microns (0.01 millimeters).

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.

In the peripheral nervous system, abnormal accumulation of lipofuscin known as lipofuscinosis[1] is associated with a family of neurodegenerative disorders – neuronal ceroid lipofuscinoses, the most common of these is Batten disease.

Also, pathological accumulation of lipofuscin is implicated in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, certain lysosomal diseases, acromegaly, denervation atrophy, lipid myopathy, chronic obstructive pulmonary disease,[16] and centronuclear myopathy. Accumulation of lipofuscin in the colon is the cause of the condition melanosis coli.

Micrograph showing lipofuscin, in brown/yellow, in a liver biopsy with ground glass hepatocytes; H&E stain. High magnification micrograph of ground glass hepatocytes, as seen in a chronic hepatitis B infection with a high viral load. Liver biopsy. H&E stain. Lipofuscin (fine brown/yellow granular pigment) is seen in several of the hepatocytes. See also Image:Ground glass hepatocytes high mag.jpg – uncropped version of this image. Image:Ground glass hepatocytes intermed mag.jpg – intermediate magnification view. Image:Ground glass hepatocytes high mag cropped 2.jpg – cropped version of another high magnification image – different case.

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

Possible therapies

Calorie restriction,[4] vitamin E,[4] and increased glutathione appear to reduce or halt the production of lipofuscin. (tracking glutathione at All This)

The nootropic drug piracetam appears to significantly reduce accumulation of lipofuscin in the brain tissue of rats.[18]

Other possible treatments:

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. (maybe just lay off the sunscreen?)

Micrograph of heart muscle showing lipofuscin pigment, H&E stain. Department of Pathology, Calicut Medical College – Calicut Medical College
Cardiac myocyte showing fine yellow brown lipofuscin granules in the perinuclear region [H&E stain 100X]

Soraprazan (remofuscin) has been found to remove lipofuscin from retinal pigment epithelial cells in animals.[23] 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.[24]

Other uses

Lipofuscin quantification is used for age determination in various crustaceans such as lobsters and spiny lobsters.[25][26] 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.

See also

References

  1. ^ Jump up to:a b Alberts, Daniel Albert (2012). Dorland’s illustrated medical dictionary (32nd ed.). Philadelphia, PA: Saunders/Elsevier. p. 1062. ISBN 978-1-4160-6257-8.
  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. ^ Jump up to:a b c Chris Gaugler, “Lipofuscin Archived 2007-07-15 at the Wayback Machine“, Stanislaus Journal of Biochemical Reviews May 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. PMID 18278576. S2CID 6833509.
  6. ^ “lipochrome”, The Free Dictionary, retrieved 2021-02-18
  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. PMID 9888441.
  8. ^ Terman, Alexei; Brunk, Ulf T. (1999). “Is Lipofuscin Eliminated from Cells?”. Investigative Ophthalmology and Visual Science. 40 (10): 2463–2464. PMID 10476822.
  9. ^ Davies, Sallyanne; Ellis, Steven (1999). “Lipofuscin Turnover”. Investigative Ophthalmology and Visual Science. 40 (8): 1887–1888. PMID 10393067.
  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. PMID 9541135. S2CID 34448638.
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  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. PMID 11870715. S2CID 22309073.
  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. ISSN 2045-2322. PMC 6397159. PMID 30824797.
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  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. PMID 6416880. S2CID 29129359.
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  26. ^ Kerry E. Maxwell; Thomas R. Matthews; Matt R. J. Sheehy; Rodney D. Bertelsen; Charles D. Derby (2007). “Neurolipofuscin is a measure of age in Panulirus argus, the Caribbean spiny lobster, in Florida”. The Biological Bulletin. 213 (1): 55–66. doi:10.2307/25066618. JSTOR 25066618. PMID 17679720. S2CID 8522101.

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

External links for general reviews

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From Wikipedia where this page was last edited on 9 January 2022,

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