The name, age spot is usually used to indicate a pigment spot on the skin. within this article, we use both ceroid and lipofuscin to indicate an “agespot”. Let’s start with ceroid first.
Ceroids
Around 1883, Schultz theorizes that pigmentation of human ganglion cells increased with age. In 1889, White, showed that pigmentation in human ganglion cells were more frequent than other mammals. In 1894, Goebel noticed ceroid like products in the digestive smooth muscle of human digestive systems[i]. That same year Hogde demonstrated, by examining the cells of cerebrum, cerebellum, cervical spinal cord of individuals, ranging from babies to elderly, that in young specimens no pigment was found while pigmentation was clearly present in the elderly. It took about 50 years before the name ceroid was coined in 1941 by Lillie, Ashburn, Sebrell, Daft, and Lowry. These scientists described ceroid as a yellow-like lipoid pigment that occurs in the cirrhotic livers of choline-deficient rats, before this, other scientist found that low protein favored the accumulation of ceroids[ii], the greatest accumulation was found by the addition of unsaturated fats. The alpha-tocopherol (vitamin E) was found to protect and delay the onset of ceroids in studies, even after the addition of cod liver oil. All through 1940-1950, studies accumulated and showed that pigmentation was associated with aging. This accumulated in 1957 as it was stated that :
one of the most reliable changes in the nervous stystem is the accumulation of pigment inside the neurons[iii]
In the 1950s Schornagel investigated the hearts and arteries of people that have died from various conditions and found that increased iron deposits and ceroids were found in aged hearts that had died of heart infarctions. Schornagel reasoned that among other items, high nutritional demands, can increase the width of the arteries and make these arteries prone to rupture hemorrhages, even in an early age. These hemorrhages in turn can cause scarring lesions that can become potential points for arteriosclerosis in the future. These lesions in an early age are clear of cholesterol deposits. In the 1960s it was found that fish oils were superior in forming ceroids when to compared to soy-oils[iv]. The pigmentation occurred due to a combination of transition metals, proteins, and especially unsaturated fats. In vitro experimentations show that ceroids-like material could be produced with unsaturated fatty acids. There was discussion that the intake of unsaturated fatty acid in the diet could severely influence the rate of pigmentation forming, while saturated fats were found to be inert[v].
The accumulation of ceroids was found in humans in the aorta, blood vessels, lymph gland, spleen, liver, adrenals, kidneys, testis, seminal vesicles, ovary, uterus, skeletal muscle, pituitary gland, and central nervous system (ganglion cells cortex, thalamus, medulla, spinal cord, microglia, oligodendroglia)[vi]. The research went further and it was found that the fish-eating (especially fermented fish) eating population had an abundance of ceroids in the intestines[vii].
Lipofuscin
As the ceroids are found almost all over the body, lipofuscin is mostly found in postmitotic cells (heart, nerve, and brain cells[viii]) but also found in organs that have a lot of unsaturated fats, predominantly in the liver, retina, adrenals. These cells are thought to mature and are incapable of mitosis (a division of the nucleus to produce copies).
It was shown that the iron-induced non-enzymatecally oxidizing lipids (especially unsaturated fats) attack proteins that form dysfunctional products possibly leading to lipofuscin[ix]. The research in 1984 showed that when rats were fed different fat sources (olive, lard, control, and sunflower). The lard contained more 22:6 3 (fish oil) than the other fat sources. Looking at lipofuscin the hippocampus in the brain, there was no difference between sunflower and olive oil, but was significantly increased with the lard, it was concluded that the increase in lipofuscin was associated with 22:6 (DHA omega 3) content in the hippocampus and not with the gross peroxidation of the source fat[x].
It has been shown that an antagonist of the 5-HT receptor (which result in decreased serotonin) can decrease lipofuscin formation, increase the health of the mitochondria and protect the retina. Omega 3 is used for serotonin formation[xi], a deficiency in omega 3 can result in decreased serotonin production, seemingly independent from estrogen[xii].
As the research progressed it was found that ceroid are associated aging and the accumulation of lipofuscin is associated with aging and longevity is inversely associated with lipofuscin[xiii].
Because lipofuscin cannot be (easily) degraded and can build up inside the cell, this, in turn, can result in enlargement and structural disorganization of the mitochondria, which, in turn, results in decreased energy production seen in many pathologies[xiv]. Decreased mitochondria function results in decreased function of lysosomal function[xv]. The lysosomal enzymes still work on trying to degrade lipofuscin, they can’t be working on other products[xvi].
This lipofuscin can be seen after short-term fish oil supplementation. In rats, lipofuscin in cardiac myocytes can be induced after a 4 week fish oil supplemention[xvii].
Lipofuscin in the hippocampus is associated with a decline in learning and memory[xviii]. When lipofuscin is 70 % or greater of the content of a neuron, the neuron will likely die[xix]. DHEA and testosterone were found to be protective against lipid peroxidation and lipofuscin formation[xx][xxi]. Temperature is of great importance in the formation of lipofuscins, as it was shown that the amount of lipofuscin was almost doubled when fish were compared in 20 C to 30 C degrees [xxii]. As in agreement with other studies, the higher degree of temperature saw a lower mortality rate.
Again, these oils are meant to function at body temperatures of 37 C degrees!
Although lipofuscins are positively associated with aging and death the good news is that it is heavily associated with nutritional intake and status and not with your genetic blueprint[xxiii]
[i] GOEBEL, C. Ueber Pigmentablagerung in der Darmmusculatur. Virchow Arch Path Anat z36:482-522, I894
[ii] Gyorgy, P., and Goldblatt, H., J. Exp. Med., 1942, 75, 355. OBSERVATIONS ON THE CONDITIONS OF DIETARY HEPATIC INJURY (NECROSIS, CIRRHOSIS) IN RATS.
[iii] Genesis of Intracellular Pigment in the Spinal Ganglia of Senile Rats. An Electron icroscope Study. William Bondareff, Ph.D. J Gerontol (1957) 12 (4): 364-369. DOI: https://doi.org/10.1093/geronj/12.4.364 Published: 01 October 1957.
[iv] Nutritional study of ageing. 4. Effect of fish oil on the appearance of ceroid pigment in rats. KOYANAGI, T.; FURUKAWA, R.; MIYASHI, K. Journal article : Journal of Japanese Society of Food and Nutrition 1969 Vol.22 pp.148-151
[v] THE IN VITRO PREPARATION AND HISTOCHEMICAL PROPERTIES OF SUBSTANCES RESEMBLING CEROID* BY W. G. BRUCE CASSELMAN,$ M.D. (From the Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada) PLATE 39 (Received for publication, August 4, 1951)
[vi] “CEROID” PIGMENT IN HUMAN TISSUES * ALwIN M. PAPPENHEIMER, M.D.,t and JOSEPH VICTOR, M.D. (From the Department of Pathology, College of Physicians and Surgeons, Columbia University, and from the First Division, Research Service, Goldwater Memorwl Hospital, New York, N. Y.)1945.
[vii] CEROID IN THE GASTROINTESTINAL SMOOTH MUSCLE OF TIE THAI-LAO ETHNIC GROUP. SYLVANUS W. NYE, M.D.,* AND KASEM CHITrAYASOTHORN, M.D.t From the Geographic Pathology Division, Armed Forces Institute of Pathology, and the Walter Reed Army Institute of Research, Washington, D.C., in conjunction with the U. S. Army Component, SEATO Medical Research Laboratory, Bangkok, Thailand
[viii] This author doesn’t think that for example heart cells are post-miotic. Life and Death of ardiac Stem Cells Piero Anversa, Jan Kajstura, Annarosa Leri and Roberto Bolli. Circulation. 2006;113:1451-1463, originally published March 20, 2006.
[ix] Iron-Induced Accumulation of Lipofuscin-like Fluorescent Pigment in the Retinal Pigment Epithelium Martin L. Katz, Holly J. Stientjes, Chun-Lan Gao, and J. Scott Christianson
[x] Brizzee, K.R., Eddy, D.E., Harman, D. et al. AGE (1984) 7: 9. doi:10.1007/BF02431889
[xi] Thampi P, Rao HV, Mitter SK, et al. The 5HT1a Receptor Agonist 8-Oh DPAT Induces Protection from Lipofuscin Accumulation and Oxidative Stress in the Retinal Pigment Epithelium. Gonzalez P, ed. PLoS ONE. 2012;7(4):e34468. doi:10.1371/journal.pone.0034468.
[xii] McNamara RK, Able J, Liu Y, et al. Omega-3 Fatty Acid Deficiency During Perinatal Development Increases Serotonin Turnover in the Prefrontal Cortex and Decreases Midbrain Tryptophan Hydroxylase-2 Expression in Adult Female Rats: Dissociation from Estrogenic Effects. Journal of psychiatric research. 2009;43(6):656-663. doi:10.1016/j.jpsychires.2008.09.01.
[xiii] Free Radical Biology and Medicine. Volume 33, Issue 5, 1 September 2002, Pages 611–619. Serial review: oxidative stress and aging. Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Ulf T Brunk, Alexei Terman
[xiv] Eur J Biochem. 2002 Apr;269(8):1996-2002. The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Brunk UT, Terman A.
[xv] Cell Metab. 2015 Sep 1;22(3):485-98. doi: 10.1016/j.cmet.2015.07.020. Epub 2015 Aug 20. Mitochondrial Respiration Controls Lysosomal Function during Inflammatory T Cell Responses. Baixauli F1, Acín-Pérez R2, Villarroya-Beltrí C1, Mazzeo C3, Nuñez-Andrade N1, Gabandé-Rodriguez E4, Ledesma MD4, Blázquez A5, Martin MA5, Falcón-Pérez JM6, Redondo JM7, Enríquez JA2, Mittelbrunn M8.
[xvi] Heart, Lung and Circulation. Volume 14, Issue 2, June 2005, Pages 107–114. Current Review. The Aging Myocardium: Roles of Mitochondrial Damage and Lysosomal Degradation. Alexei Termana Ulf T. Brunk.
[xvii] Ultrastructural and Biochemical Evidence of Cardiac Lipofuscinosis after Short-term Intake of Fish Oil in Rats. Atsuo Yanagisawa,
[xviii] Flood, J. F., et al. Age-related changes in learning, memory, and lipofuscin as a function of the percentage of SAMP8 genes. Physiol Behav. 58(4):819-822, 1995
[xix] Jarvik, L. F. The aging nervous system: Clinical aspects. Aging. Raven Press, New York, 1975, Volume 1:1-9
[xx] Age-induced apoptosis in the male genital tract of the mouse M Jara, R Carballada and P Esponda. Centro de Investigaciones Biolo´gicas, CSIC, Vela´zquez 144, 28006-Madrid, Spain. Correspondence should be addressed to Pedro Esponda; Email: esponda@cib.csic.es. 2004
[xxi] Biogerontology. 2008 Aug;9(4):235-46. doi: 10.1007/s10522-008-9133-y. Epub 2008 Feb 29. Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions. Kumar P1, Taha A, Sharma D, Kale RK, Baquer NZ.
[xxii] Hsu, C.-Y. and Chiu, Y.-C. (2009), Ambient temperature influences aging in an annual fish (Nothobranchius rachovii). Aging Cell, 8: 726–737. doi:10.1111/j.1474-9726.2009.00525.x
[xxiii] Mech Ageing Dev. 1980 Feb;12(2):183-95. Accumulation of lipofuscin pigment in human hepatic cells from different races and in different environmental conditions. Tauchi H, Hananouchi M, Sato T.