Fight Aging!

Mitochondria are the bacteria-like power plants of the cell, thousands to each cell, and each mitochondrion bearing its own DNA separate from that in the cell nucleus. Damage to this DNA is important in aging, and in a variety of diseases. Mitochondrial disease and mitochondrial contributions to degenerative aging are two very different things, however, for all that they both involve damage to mitochondrial DNA. In mitochondrial disease most of a patient's mitochondria have the same form of mutational damage, inherited from the mother or generated very early in embryonic growth. In aging the damage is random between cells, but there are certain forms of mutational damage that become amplified because they make a damaged mitochondrion more likely to survive and replicate in comparison to its undamaged peers.

Here is an interesting, albeit minority view on mitochondrial damage and how cells respond to it. It is of more relevance to mitochondrial disease, but there are aspects of it that might be informative with respect to cells in old tissues overtaken by damaged, dysfunctional mitochondria:

The new research shows that small changes in the ratio of mutant to normal mitochondrial DNA within the thousands of mitochondrial DNAs inside each cell can cause abrupt changes in the expression of numerous genes within the nuclear DNA. "By showing that subtle changes in the cellular proportion of the same mitochondrial DNA mutation can result in a wide range of different clinical manifestations, these findings challenge the traditional model that a single mutation causes a single disease. The research offers key insights into understanding the underlying cause of metabolic and neurodegenerative disorders such as diabetes, Alzheimer, Parkinson and Huntington disease, as well as human aging. The discrete changes in nuclear gene expression in response to small increases in mitochondrial DNA mutant level are analogous to the phase changes that result from adding heat to ice. As heat is added, the ice abruptly turns to water and with more heat, the water turns abruptly to steam."

[Researchers investigated] levels of a pathogenic mutation in one particular base of mitochondrial DNA. Researchers already knew that if 10 to 30 percent of a person's mitochondrial DNA has this mutation, a person has diabetes, and sometimes autism. Individuals with an mtDNA mutation level of 50 to 90 percent have other multisystem diseases, particularly MELAS syndrome, a severe condition which involves brain and muscle impairments. Above the 90 percent level, patients die in infancy. In the current study, conducted in cultured human cells, [the researchers] analyzed cells with different levels of this pathogenic mtDNA mutation to determine the effects on the gene expression of the cell. The researchers measured variations in cellular structure and function, nuclear gene expression, and production of different proteins.

The gene expression profile - the pattern of gene activity seen at the level at which mtDNA mutations trigger brain disorders - parallels the profiles found in Alzheimer, Parkinson and Huntington diseases. "The findings in this study provide strong support for the concept that common metabolic diseases such as diabetes and obesity, heart and muscle diseases, and neurodegenerative diseases have underpinnings in energy deficiencies from malfunctioning mitochondria. Thus this concept brings together a cluster of diseases previously considered to be separate from one another."

Link: http://www.chop.edu/news/steadily-rising-increases-mitochondrial-dna-mutations-cause-abrupt-shifts-disease