Lipopigments

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Lipopigments are lipid-derived toxic fluorescent pigments that are a byproduct of human metabolism and which accumulate with age.

A principal marker of brain vulnerability, stress, aging, and related pathology is represented by lipopigments – lipofuscin and ceroid. During ontogenesis, neuronal lipopigment accumulations are significantly correlated with important changes in nerve cell morphology and biochemistry.

In the aged neurons, lipopigments are present in all cellular compartments. Moreover, neuronal lipopigment accumulations coexist with glial lipopigment storage, especially in microglia. Owing to their transporting properties, and the migration capacity of microglia, glial cells deposit lipopigment clusters in pericapillary areas. Thus, lipopigment conglomerates appear in the whole nervous tissue.

There are two types of lipopigments:

  • Ceroid
  • Lipofuscin

The recycling centers inside of cells are lysosomes. Tiny bags of digestive enzymes sealed in a membrane skin, these organelles take apart damaged or unneeded proteins, lipids, and mitochondria.

However, occasionally, the lysosome will take in an abnormal chemical structure which resists degradation by lysosomal enzymes. This just stays inside the lysosome, eventually joined by other abnormal structures.

During the lifespan of an animal, lysosomes in postmitotic cells accumulate a lot of this highly cross-linked organic substance called “lipofuscin” or “ceroid”. Late in life, many of these lysosomes have so much lipofuscin that they are less able to recycle the proteins, lipids, and mitochondria. Consequently, damaged mitochondria accumulate in these cells, lowering ATP production and increasing ROS production.

Lipofuscin may also cause lysosomes to leak degradative enzymes and ROS into the cytoplasm, causing further damage to cellular components.

Lipofuscin may also absorb heavy metals such as Mercury and Aluminium as well as nutritional elements such as Zinc and Copper. Lipofuscin is there a matrix in which heavy metals are retained in the cells of the body.

Lipofuscin is not toxic in of itself, but the effect of its presence can have extremely detrimental effects on the cell and accelerate the ageing process. Lipofuscin tends to agglutinate or clump together, forming a sludge.

The agglutination tends to clog up cellular membranes, reduce their fluidity and cause cellular dehydration – resulting in less efficient enzymatic cellular reactions and less efficient DNA and RNA transcription and translation. Lack of cellular membrane fluidity also results in impairment of normal Sodium, Potassium and Calcium transport in and out of the cell, reducing cellular communication (i.e. prevents synapses from releasing neurotransmitters that allow communication of information between nerve cells) and fluid flow. Dehydrated cells tend to dissipate heat less easily from enzymatic reactions. Intracellular temperatures thus tend to increase which also has the effect of increasing the amount of harmful, rogue glycation of proteins, resulting in a vicious circle of Lipofuscin build up and cellular ageing and degeneration. When Liposfuscin levels reach a critical threshold concentration the cell may die.

Prof. Imre Zs. Nagy discovered that the cells that make up young bodies comprise 92% water and lipids, and 8% dry mass. Conversely, elderly bodies comprise only 40% water and lipids, and 60% dry mass.

As we grow older the cell membrane becomes less lipid (less watery and more solid). This impedes its efficiency to conduct normal function and in particular there is a toxic accumulation. This cellular toxin is referred to as lipofuscin and as we grow older lipofuscin deposits become more present in the brain, heart and lungs and also in the skin. Indeed some of the skin age-pigments referred to as liver or age-spots are composed of lipofuscin. It is known that Alzheimer Disease patients have much higher levels of lipofuscin deposits than compared to their healthy controls.

Ceroid

Ceroid may accelerate the progression of the aging process by inhibiting the ability of Proteolytic Enzymes and Lipases to degrade damaged Endogenous Proteins in Cells and thereby facilitating the accumulation of damaged Endogenous Proteins in Cells.

Lipofuscin

Lipofuscin is the name given to finely granular yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion.

Lipofuscion

It is commonly found in the liver, kidney, heart muscle, retina, adrenals, nerve cells, and ganglion cells.

The loss of mitochondrial function can cause the buildup of aging pigments known as lipofuscin. Lipofuscin builds up when a cellular “garbage-disposal system” (i.e., autophagy) breaks down. Eventually, with the decrease in autophagy and related increase in lipofuscin, there is increased oxidative stress, decreased energy production, and ultimately, cell death.

Eventually, with the decrease in autophagy and related increase in lipofuscin, there is increased oxidative stress, decreased energy production, and ultimately, cell death.

It 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, aluminum, iron, copper and zinc.


References:

Lipopigments and Aging Nervous System 

http://www.legendarypharma.com/senescence.html

Sitte, N., et al. Proteasome inhibition by lipofuscin/ceroid during postmitotic aging of fibroblasts FASEB. 14(11):1490-1498, 2000.

De Meyer GR, De Keulenaer GW, Martinet W. Role of autophagy in heart failure associated with aging. Heart Fail Rev. 2010 Sep;15(5):423-30.

Petrovski G, Das DK. Does autophagy take a front seat in lifespan extension?   J Cell Mol Med. 2010Nov;14(11):2543-51.

Terman A 1, Brunk UT. Lipofuscin.  Int J Biochem Cell Biol. 2004 Aug;36(8):1400-4.

Chris Gaugler, “Lipofuscin”, Stanislaus Journal of Biochemical Reviews May 1997


Download PDF:  Tables – Neurotoxic Effects of Lipofuscin and Substances that Inhibit the Formation of Ceroid and Lipofuscion


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