The accumulative waste theory of aging, also known as the waste accumulation or garbage accumulation theory of aging, proposes that molecules damaged by oxidation and their by products (e.g., aged collagen, damaged enzymes), and damaged mitochondria (organelles responsible for cellular energy production) accumulate in postmitotic (non dividing cells) causing dysfunction, toxicity, aging, and cell death (see Error Catastrophe Theory of Aging).
There are several mechanisms by which garbage accumulation affects cells. The presence of waste products changes the structural organization of the cell. Cellular components are displaced by these waste products and cellular functions such as cell signaling, transport of cellular molecules, and metabolic functions are impeded. Accumulation of waste materials within the cell can also cause damage, secondary to their toxicity, for example by the accumulation of toxic protein oxidation products in the cell or by an increased amount of reactive oxygen species (highly reactive molecules that react with, and damage, cell components) produced by damaged mitochondria.
Postmitotic cells, for example cardiac and skeletal muscle cells as well as nerve cells, are particularly susceptible to the accumulation of damaged cellular components and non degradable waste products, due to their lack of turnover. Actively dividing cells are capable of ‘‘diluting’’ the amount of damage during cell division. Cells like those of the intestinal tract and blood cells experience rapid turnover, and die or are replaced before waste materials can accumulate to a detrimental level within the cell; in this regard, mitosis and rapid turnover of cells are protective against aging. This mechanism of waste accumulation and protection has been shown in experimental studies, by comparing the waste accumulation in dividing cells with that of non dividing cells.
Lipofuscin
Lipofuscin, composed of brownish yellow oblong granules, is a cellular waste product caused by the peroxidation (free-radical reaction) of proteins with lipid molecules. This waste product appears to play a key role in the accumulative waste process, both by its own accumulation and by associated events (e.g., oxidative damage) that produce a cycle of waste accumulation. Under normal conditions, waste molecules are taken up and degraded by cellular lysosomes (organelles within the cell that contain an acidic material for digestion of foreign and damaged cellular materials). Because of their molecular structure, lipofuscin molecules are not effectively digested within lysosomes, leading to lipofuscin accumulation over time. This results in the reduced ability of the lysosome to perform its normal functions, both due to ineffective use of lysosomal enzymes as well as by causing dysfunction of the proton pump (acid pump like those present in the stomach) necessary for lysosomes to create an internal environment capable of digestion’s problem. Lipofuscin molecules also contain a small percentage of metals like iron.
Accumulation and concentration of iron in the lysosome can contribute to free-radical reactions, leading to a vicious cycle resulting in increased lipofuscin accumulation, in addition to increased free-radical damage of other cellular components. Lipofuscin preferentially accumulates in postmitotic cells, accelerating the aging process and level of dysfunction in these cell types, with minimal damage to mitotic cells.
Waste Accumulation and Aging
In general, aging cells have a decreased ability to properly degrade cellular waste products; however, there may be inter individual variation in the efficiency of waste degradation and the amount of lipofuscin accumulation that will occur. One explanation may be variability in an individual’s genetic profile that will determine the properties and digestive capabilities of the person’s cellular lysosomes. The variation may be reflective of the environment or the health and nutritional status of the person.
Public Health Perspective
Waste accumulation has been the target of anti aging remedies. Methods to increase the functionality of the cellular waste degradation process may show promise for preventing the effects of cellular waste accumulation on cellular aging and cell death. These measures may involve nutritional or enzyme supplementation, to reduce lipofuscin accumulation or to prevent the excess production of frees radicals in the cell; however, more research is necessary in the development and testing of these products. As is a common theme in the prevention of cellular damage and aging, every individual (young and old) should strive to live a healthy lifestyle including regular physical activity and endurance training, with a balanced diet, rich in antioxidants and essential nutrients.
Even small positive lifestyle modifications have the potential to result in significant improvements in the health, well-being, and longevity of our population.
