One of the more-traditional theories of aging covered in my anti-aging treatise is Lipofuscin accumulation, a theory that has been around for decades. According to this theory, aging is caused by or contributed to by lipofuscin, metabolic gunk, oxidized cross-linked proteins, that accumulates in postmitotic cells with age and gums up their workings. It is found in a variety of cell types in a variety of organs including the heart, kidney, liver, eyes and brain. Levels of lipofuscin are often used as biomarkers of age. I recently started to wonder if this theory was too stodgy compared to newer sexier theories like Programmed epigenomic changes. So, I decided to do a check on lipofuscin-related research. I came up with several items suggesting that despite all the aging-related research in newer areas of genomics and molecular biology, lipofuscin accumulation continues to be of great importance in aging.
o Lipofuscin continues to be studied. A search in pubmed.org on “lipofuscin 2009” reveals 150 citations. According to a review study, “Lipofuscin formation appears to depend on the rate of oxidative damage to proteins, the functionality of mitochondrial repair systems, the proteasomal system, and the functionality and effectiveness of the lysosomes. This review highlights the current knowledge of the formation, distribution, and effects of lipofuscin in mammalian cells(ref).”
o Cells have mechanisms for protein repair and a mechanism for getting rid of damaged proteins called proteolysis which happens due to specialized protein complexes in cells called proteasomes. “Therefore, the accumulation of oxidized protein with age can be due to increased protein damage, decreased oxidized protein degradation and repair, or the combination of both mechanisms. The proteasomal system is the major intracellular proteolytic pathway implicated in the degradation of oxidized protein, –(ref).” In plain language words, lipofuscin accumulation is due to an imbalance in cell metabolic and waste-degradation functions.
o Large accumulations of lipofuscin and lipofuscin-like materials in cells can lead to cell death. “The results of this study are consistent with the conclusion that accumulation of lipofuscin-like materials results in inhibition of the proteasome, which initiates an apoptotic cascade as a result of dysregulation of several proapoptotic proteins(ref).
· According to Encylopedia Britannica “The pigment lipofuscin accumulates within heart muscle cells; it is not detectable at ten years of age but rises to almost 3 percent of the cell volume by age 90(ref).”
· ”This review article covers how lipofuscin and neuromelanin, a related substance, accumulated with age in autophagic vacuoles in neurons and the damage created. “The most striking morphologic change in neurons during normal aging is the accumulation of autophagic vacuoles filled with lipofuscin or neuromelanin pigments. — The pigments arise from incompletely degraded proteins and lipids principally derived from the breakdown of mitochondria or products of oxidized catecholamines. Pigmented autophagic vacuoles may eventually occupy a major portion of the neuronal cell body volume because of resistance of the pigments to lysosomal degradation –(ref).”
· There is a family of at least eight rare and genetically distinct neurodegenerative diseases associated with accumulation of lipofuscin in cells known as neuronal ceroid lipofuscinoses (NCL)(ref)(ref). “They (the NCL diseases) are associated with variable yet progressive symptoms including seizures, dementia, visual loss, and/or cerebral atrophy(ref).”
· The tyrosinase gene is involved in the deposition of cardiac lipofuscin, at least in mice(ref). This is a relatively older (1993) finding. “Analysis of spontaneous mutants of the tyrosinase gene, encoded by the albino locus, confirmed that the tyrosinase gene itself controls lipofuscin formation.” “Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation, as in the blackening of a peeled or sliced potato exposed to air(ref).” So it is a good guess that black lipofuscin skin spots on older people are created by a somewhat similar process to that which turns a sliced potato black.
· Lipofuscin is often considered in a broader context as one of several forms of undesirable protein aggregations, others sometimes being called ceroids, inclusion bodies, plaques, or aggresomes depending on their source and composition. While possibly being metabolic products, these aggregations may be biologically active. They may affect proteasomal activity and protein turnover and are common features of neurodegenerative diseases as well as aging(ref).
· A diagram of how lipofuscin buildup reduces the effectiveness of cellular lysomes capability to degrade damaged mitochondria can be found here.
· Acumulation of lipofuscin in the retinal pigment epithelium (RPE) has long thought to be a major factor leading to age-related dry macular degeneration(ref)(ref). There is a substantial literature on this subject.
These and many other research reports I encountered continue to indicate that lipofuscin accumulation is serious issue in aging.
Lipofuscin accumulation is closely associated with things that happen according to other major theories of aging such as Oxidative Damage and Chronic or Excess Inflammation. For example, in the case of AMD (adult macular degeneration), “These findings link four factors that have been posited as being associated with: inflammation, oxidative damage, drusen, and RPE lipofuscin(ref).”
Protection against oxidative damage is one key strategy for minimizing the production of li[pofuscin. See the firewall for the oxidative damage theory of aging, both lifestyle elements and dietary supplements. Fortunately, there are several supplements with serve either to reduce levels of lipofuscin accumulation or to help pump lipofuscin out of cells. They are listed in the firewall for the lipofuscin accumulation theory of aging.