Unsaturated Fats and Age Pigment

Also see:
Foods That Prevent Aging Skin by Emma Sgourakis

“An editorial by Pinckney in the June 1973 issue of the American Heart Journal reviews evidence that the unsaturated fats hasten aging of the skin, are toxic to the both animals and man, and furthermore, that use of such diets has not prevented heart attack.” -Broda & Charlotte Barnes

Quotes by Ray Peat, PhD:
“In the 1960s, Hartroft and Porta gave an elegant argument for decreasing the ratio of unsaturated oil to saturated oil in the diet (and thus in the tissues). They showed that the “age pigment” is produced in proportion to the ratio of oxidants to antioxidants, multiplied by the ratio of unsaturated oils to saturated oils. More recently, a variety of studies have demonstrated that ultraviolet light induces peroxidation in unsaturated fats, but not saturated fats, and that this occurs in the skin as well as in vitro. Rabbit experiments, and studies of humans, showed that the amount of unsaturated oil in the diet strongly affects the rate at which aged, wrinkled skin develops. The unsaturated fat in the skin is a major target for the aging and carcinogenic effects of ultraviolet light, though not necessarily the only one.”

“Lipofuscin, or age-pigment, is related to the oxidation of unsaturated fats, and has been proposed to be such a material, that progressively limits a cell’s adaptive capacity because of its physical and chemical properties.”

“Estrogen, at least when it is not opposed by a very large concentration of progesterone, creates all of the conditions known to be involved in the aging process. These effects of estrogen include interference with oxidative metabolism, formation of lipofuscin (the age-pigment), retention of iron, production of free radicals and lipid peroxides, promotion of excitotoxicity and death of nerve cells, impaired learning ability, increased tendency to form blood clots and to have vascular spasms, increased autoimmunity and atrophy of the thymus, elevated prolactin, atrophy of skin, increased susceptibility to a great variety of cancers, lowered body temperature, lower serum albumin, increased tendency toward edema, and many of the features of shock. In recent years, it has been found to be responsible even for neonatal masculinization and the masculinization of the polycystic ovary syndrome. Although the pharmaceutical industry has often referred to it as “the female hormone,” I don’t know of any competent scientist who has ever called it that.”

“Around the beginning of the 20th century, it was commonly believed that aging resulted from the accumulation of insoluble metabolic by-products, sort of like the clinker ash in a coal furnace. Later, age pigment or lipofuscin, was proposed to be such a material. It is a brown pigment that generally increases with age, and its formation is increased by consumption of unsaturated fats, by vitamin E deficiency, by stress, and by exposure to excess estrogen. Although the pigment can contribute to the degenerative processes, aging involves much more than the accumulation of insoluble debris; aging increases the tendency to form the debris, as well as vice versa.”

“The lesions of atherosclerosis and cataracts contain some of the same oxidized lipids as the age pigment itself. When large deposits of age pigment become visible, it’s probably because the general reduction of metabolism and protein synthesis has interfered with the normal processes for removing debris. The age pigment contributes to degeneration by wasting energy and oxygen, weakening the antioxidation, antiglycation, and other defensive systems.”

“When I was studying the age pigment, lipofuscin, and its formation from polyunsaturated fatty acids, I saw the 1927 study in which a fat free diet practically eliminated the development of spontaneous cancers in rats (Bernstein and Elias). I have always wondered whether George and Mildred Burr were aware of that study in 1929, when they published their claim that polyunsaturated fats are nutritionally essential. The German study was abstracted in Biological Abstracts, and the Burrs later cited several studies from German journals, and dismissively mentioned two U.S. studies* that claimed animals could live on fat-free diets, so their neglect of such an important claim is hard to understand. (*Their bibliography cited, without further comment, Osborne and Mendel, 1920, and Drummond and Coward, 1921.)”

“Age pigment, lipofuscin, is produced in oxygen deprivation, apparently from reduced iron which attacks unsaturated fats. It has its own “respiratory” activity, acting as an NADH-oxidase. Melanin is produced by polymerization of amino acids, with copper as the catalyst. With aging, iron tends to replace copper. Melanin is an antioxidant. Thus, there is a sort of reciprocal relationship between the two types of pigment. A vitamin E deficiency relative to consumption of polyunsaturated fats, and an estrogen excess, accelerate the formation of lipofuscin.

A 47 year-old woman who had only a few “liver spots” on the backs of her hands began taking large amounts of estrogen, and within a few months the brown spots had darkened and spread until most of her skin was covered with spots. When she stopped using estrogen, and applied progesterone topically, the spots disappeared.”

“The unsaturated oils have been identified as a major factor in skin aging. For example, two groups of rabbits were fed diets containing either corn oil or coconut oil, and their backs were shaved, so sunlight could fall directly onto their skin. The animals that ate corn oil developed prematurely wrinkled skin, while the animals that ate coconut oil didn’t show any harm from the sun exposure. In a study at the University of California, photographs of two groups of people were selected, pairing people of the same age, one who had eaten an unsaturated fat rich diet, the other who had eaten a diet low in unsaturated fats. A panel of judges was asked to sort them by their apparent ages, and the subjects who consumed larger amounts of the unsaturated oils were consistently judged to be older than those who ate less, showing the same age-accelerating effects of the unsaturated oils that were demonstrated by the rabbit experiments.

While it is important to avoid overexposure to ultraviolet light, the skin damage that we identify with aging is largely a product of our diet.”

“The shorter chain fatty acids of coconut oil are more easily oxidized for energy than long chain fatty acids, and their saturation makes them resistant to the random oxidation produced by inflammation, so they don’t support their production of acrolein or age pigment; along with their reported antiinflammatory effect, these properties might be responsible for their beneficial effects that have been seen in Alzheimer’s disease.”

Adv Exp Med Biol. 1989;266:3-15.
Lipofuscin and ceroid formation: the cellular recycling system.
Harman D.
Lipofuscin, age pigment, is a dark pigment with a strong autofluorescence seen with increasing frequency with advancing age in the cytoplasm of postmitotic cells. By bright-field light microscopy lipofuscin appears as irregular yellow to brown granules ranging in size from 1-2 nm in diameter. The fluorescent spectra of lipofuscin in situ generally show excitation maxima at about 360 nm and a yellowish emission maxima at 540-650 nm. Ultrastructurally the granules, localized in residual body-type lysosomes, are extremely heterogeneous and vary from one cell type to another, and frequently within a single cell. The pigment granules usually contain numerous liquid droplets embedded in an electron-dense matrix. The granules stain positively for neutral lipids but are not soluble in polar or non-polar lipid solvents. Lipofuscin contains about 50 percent by weight of proteinaceous substances, a lesser fraction of lipid-like material, and probably less than one percent by weight fluorophore(s); it is enriched in metals such as Al, Cu, and Fe, and in dolichols. Free radical reactions and the proteolytic system are implicated in lipopigment formation. Thus the rate of lipopigment formation is increased by vitamin E deficiency and by increased intake of polyunsaturated fatty acids as well as by protease inhibitors such as leupeptin. Free radical reactions and proteolysis are involved in the continual turnover of cellular components. Cellular damage from free radical reactions, and others such as hydrolysis, has been present since the beginning of life. The evolution of more complex cells necessitated development of defenses – DNA repair processes, antioxidants, etc. – against damaging reactions as well as the removal and replacement of altered parts, and of those no longer needed by the cells. Proteins “marked” for disposal by oxidation damage, or other means such as conjugation with ubiquitin, are apparently rendered more hydrophobic so that they are “recognized” for degradation by the lysosomes and the proteinases and peptidases of the cytosol and mitochondria. Oxidatively altered lipids are removed by enzymes such as phospholipase A2. The products of the degradation processes are reused by the cells. Normally the recycling of damaged components works extremely well. There may be some slow slippage with advancing age as the rate of free radical damage increases while protease activity decreases. As a result a gradually increasing fraction of lysosomal “food” may be converted to non-digestible forms, lipofuscin, before it can be broken down to reusable components. Ceroid is apparently formed when the disposal system is “overloaded” or impaired.(ABSTRACT TRUNCATED AT 400 WORDS)

Ann Nutr Aliment. 1980;34(2):317-32.
[Polyunsaturated fatty acids and aging. Lipofuscins : structure, origin and development].
[Article in French]
Durand G, Desnoyers F.
In the last century, dense, pigmented bodies were observed on nerve cell sections, and the quantity of those pigments in the neurons was correlated to the age of the individual. Light microscopy has shown the presence of the pigments in the cells of most tissues and organs in both vertebrates and invertebrates, and they have also been seen in cultured cells. However, these commonly found cellular components have only have studied in detail since the last 25 years, using electron microscopic, histochemical and biochemical techniques to try to describe their nature, origin, development and possible physiological role. The comparable morphology, composition and physicochemical properties of these various pigments indicate that they are all produced by the same biochemical mechanism, including: 1) the peroxidation of the polyunsaturated fatty acids of cellular membranes by free radicals; 2) the reaction of lipid peroxidation end-products(s) with proteins, giving fluorescent polymerized compounds; 3) the combination of those polymerized elements and the peroxidized lipids. Different names have been used for these pigments, the most common of which in English are: “age pigment”, “ceroid” and “lipofuscins”. However, due to their common origin and their fluorescence, they are tended to be grouped under the term lipofuscins (in French: lipofuscines). Recent studies have confirmed that cellular lipofuscin concentration is definitely related to the physiological age of the individual. This concentration varies depending on the tissue and the organ; it is controlled by intrinsic regulatory factors, but also by environmental conditions, such as nutrition, physical activity, stress and hygienic conditions.

Adv Exp Med Biol. 1989; 266: 259-70; discussion 271.
Phospholipases and the molecular basis for the formation of ceroid in Batten Disease.
Dawson G, Dawson SA, Siakotos AN.
Lysosomal ceroid/lipofuscinosis storage in human, canine, and ovine forms of neuronal ceroidlipofuscinosis is predominantly in neurons and retinal pigment epithelial cells. Despite problems in identifying individual storage materials, it is believed that non-enzymic oxidation of unsaturated fatty acids in phospholipids and inhibition of lysosomal proteolysis, leading to massive deposition of autofluorescent pigment, is the cause of the disease. We have, therefore, studied cellular phospholipases and find a marked deficiency of lysosomal phospholipase A1 (PLA1) in canine NCL brain. Other lysosomal hydrolases, and cytosolic/mitochondrial forms of phospholipase A2 are completely normal. We believe that the PLA1 deficiency leads to transient lysosomal storage of phospholipids containing peroxy fatty acids which are then chemically converted to hydroxynonenal, a potent inhibitor of a thiol-dependent enzymes. Inhibition of proteases is believed to be intrinsic to the formation of lipofuscin. An inherited deficiency of a thiol protease (the lysosomal cathepsin H) in two siblings with NCL can also lead to build up of peptides which are then cross-linked and converted into ceroid-containing curvilinear bodies. Thus there is evidence for molecular and genetic heterogeneity in Batten disease.

Amino Acids. 2011 May;40(5):1297-303. doi: 10.1007/s00726-011-0850-1. Epub 2011 Mar 10.
Creatine in mouse models of neurodegeneration and aging.
Klopstock T, Elstner M, Bender A.
The supplementation of creatine has shown a marked neuroprotective effect in mouse models of neurodegenerative diseases (Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis). This has been assigned to the known bioenergetic, anti-apoptotic, anti-excitotoxic and anti-oxidant properties of creatine. As aging and neurodegeneration share pathophysiological pathways, we investigated the effect of oral creatine supplementation on aging in 162 aged wild-type C57Bl/6J mice. The median healthy life span of creatine-fed mice was 9% higher than in their control littermates, and they performed significantly better in neurobehavioral tests. In brains of creatine-treated mice, there was a trend toward a reduction of reactive oxygen species and significantly lower accumulation of the “aging pigment” lipofuscin. Expression profiling showed an upregulation of genes implicated in neuronal growth, neuroprotection, and learning. These data showed that creatine improves health and longevity in mice. Creatine may, therefore, be a promising food supplement to promote healthy human aging. However, the strong neuroprotective effects in animal studies of creatine have not been reproduced in human clinical trials (that have been conducted in Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis). The reasons for this translational gap are discussed. One obvious cause seems to be that all previous human studies may have been underpowered. Large phase III trials over long time periods are currently being conducted for Parkinson’s disease and Huntington’s disease, and will possibly solve this issue.