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There are several reasons why people age and start looking older. One of the biggest reasons is the accumulation of damaged organelles and dysfunctional cells. This, in turn, makes your entire body function much worse and thus cause even more accelerated aging.
One of the main ’wear-and-tear’ aging pigments is called lipofuscin. Lipofuscin is a golden brown-looking granular pigment that contains protein, lipid, and lysosomal accumulates. It’s found in the liver, heart, muscle, and nerve cells where it deranges the processing of healthy cells.
Lipofuscin (LF) forms inside lysosomes that are organelles used to break down macromolecules and other particles via autophagy. Your body does a pretty good job in cleaning house with regular autophagy. Unfortunately, all of the parts can’t be broken down and that leads to the accumulation of lipofuscin. Why this happens is still unclear but the main reason seems to be oxidative stress.
Lipofuscin in Disease
Lipofuscin is cytotoxic because of its ability to incorporate redox-active transition metals, resulting in a redox-active surface. This promotes oxidative stress and reactive oxygen species.
Lipofuscin in heart cells is associated with heart disease and sudden cardiac death. However, that accumulation reflects more chronological aging rather than direct pathology.
Melanin and lipofuscin are considered to be hallmarks of skin aging. Skin discoloration and spots indicate liver dysfunction and lipofuscin accumulation. Those yellowish-brown spots on people’s hands and face are called liver spots but they’re lipofuscin.
LF also promotes neurodegeneration and other pathologies. It’s a major risk factor for macular degeneration.
Lipofuscin Causes
Lipofuscin contains proteins, sugars, and fats but also metals, iron, copper, and zinc. It consists of oxidized proteins and unsaturated fatty acids.
Here are the causes of lipofuscin:
- Oxidative Stress – Free radical damage of any kind injures the cells and impedes their functioning.
- Advanced Glycation End-Products (AGEs) – Proteins and fats that promote oxidative stress, aging, inflammation, and atherosclerosis.
- Cell Senescence – Accumulation of zombie cells that spread inflammation and oxidative stress.
- High Iron Levels – Too much ferritin promotes lipofuscin formation because it reacts with other macromolecules inside lysosomes. More of it will also be left in the lysosomes after degradation.
- Zinc Deficiency – Zinc is important for immune and endocrine system functioning thus it supports lysosomal degradation and autophagy. Insufficient zinc leads to the accumulation of lipofuscin in the retinal pigment epithelium of pigmented rats.
- Polyunsaturated Fats – PUFAs as they’re called, are very easily oxidized and they tend to be inflammatory in humans. Peroxidation of polyunsaturated fatty acids of cellular membranes by free radicals creates lipofuscin.
- Excess Estrogen – Estrogen is a sex hormone both men and women have but it’s more relevant during female puberty and ovulation. Too much estrogen may amplify lipofuscin formation. It increases iron absorption as well. Birth control pills also increase estrogen.
Lipofuscin causes aging and aging promotes the accumulation of lipofuscin. As your metabolism becomes less efficient with age, your ability to remove lipofuscin also diminishes. Thus you accumulate it and accelerate aging.
Lipofuscin and Autophagy
Lipofuscin accumulates primarily in the lysosomes. Autophagosomes and lysosomes are not needed for forming LF but they constitute a storage for LF aggregates. Therefore, a dysfunctional autophagy-lysosomal system plays a big role in lipofuscinogenesis.
Decreased and fawlty autophagy promotes aging in many animals and cell models], which inevitably supports lipofuscin accumulation. Impaired mitochondrial autophagy or mitophagy also contributes to lipofuscinogenesis.
It’s another chicken and an egg type of problem – as autophagy slows down you form lipofuscin, which accelerates aging and disease, thus impairing autophagy even further, and accumulating even more LF. Lipofuscin inhibits the degradation of oxidized proteins by binding to proteolytic enzymes.
Age-related diseases can be very much alleviated with sufficient clearance and autophagy. It’s one of the best preventative tools you have – to not get sick in the first place and to avoid the accumulation of lipofuscin that begins to cause more and more issues.
How to Avoid Lipofuscin Accumulation
Here’s how to avoid lipofuscin accumulation and remove it:
- Intermittent Fasting – Fasting is a potent stimulus for autophagy and cell cleanup.
- Keep Your Iron Levels Optimal – Normal ferritin levels range from 12-300 ng/ml for males and 12-150 ng/ml for women. You may get too much iron from supplements and animal protein. Alcohol increases absorption of iron. Regular blood donations and menstruation can also lower iron. Getting more copper from liver, shellfish, and chocolate helps to balance iron overload.
- Calorie Restriction – Eating fewer calories causes less oxidative stress, lowers iron, and promotes autophagy.
- Consume Autophagy Boosters – There are certain autophagy boosting foods that can fight lipofuscin and incinerate visceral fat like berberine, turmeric, cayenne pepper, coffee, green tea, and ginger.
- Manage Blood Sugar – High blood sugar promotes diabetes and AGE formation, which oxidizes fats and proteins.
- Avoid PUFAs – Fish oil supplements, vegetable oils, seed oils, and even oxidized omega-3s will cause lipid peroxidation and lipofuscin. These things will oxidize more easily in the presence of AGEs, heat exposure, oxidative stress, and excess iron.
- Don’t Smoke – Smoking promotes oxidative stress, accelerates aging, and promotes atherosclerosis. Malondialdehyde is a compound that indicates oxidative stress by smoking but it’s also found in rancid and overcooked food. Malondialdehyde also causes autoxidation of PUFAs.
- Physical Exercise – Being active improves metabolic health and body composition but it also supports autophagy. However, excess oxidative stress from too much exercise may contribute to lipofuscin. Fortunately, most people don’t train that much so you should still exercise.
- Just Enough Sunlight –
- Cyclodextrin – A compound used in drugs that stimulates autophagy and clears cellular junk, including lipofuscin.
- Vitamin E – Deficient vitamin E promotes LF accumulation and it can reduce LF as well. Vitamin E also protects against the oxidation of vitamin A, which reduces lipofuscin. Get your vitamin E from low PUFA foods like vegetables, not nuts or seeds.
- Glutathione – Reduced glutathione leads to lipofuscin formation. You stimulate glutathione with sulfur-rich foods like cruciferous vegetables, eggs, meat, and liposomal glutathione supplements.
- Creatine – Creatine has been shown to reduce free radicals and lipofuscin in the brains of rats. It also promotes cognition and muscle function.