Protein Aggregation as a Biomarker of Aging Brain

In neurodegenerative diseases, such as Alzheimer disease (AD) and Huntington disease (HD), specific proteins escape the cell’s quality-control system and associate together, forming insoluble aggregates. A study, conducted in C. elegans, has shown that widespread protein insolubility and aggregation is an inherent part of aging, and it may influence both lifespan and neurodegenerative diseases (David et al. 2010). There are ~700 proteins in a normal C. elegans that become insoluble with age. Proteins similar to those aggregating in old worms have also been identified as minor components of human disease aggregates. In the presence of proteins specific to HD actually sped up the course of the disease. About half of the aggregating proteins in AD become insoluble as a normal part of aging. The protein aggregation was significantly delayed or even halted by reducing insulin and IGF-1 hormone activity, which is known to extend animal lifespan and to delay the progression of HD and AD in animal models. The scientists also found that gene manipulations that extend the lifespan of C. elegans prevented the formation of these insoluble aggregates. Inherent protein aggregation is a new biomarker of aging. Understanding how to modulate it will lead to important insights into the mechanisms that underlie aging and protein aggregation diseases.

Telomere Shortening as a Biomarker of Aging Brain and Dementia

Telomeres are protective DNA sequences located at the ends of chromosomes that shorten with each division of the cell. Although telomeres are known biomarkers of cellular aging, their association with whole organism aging and various diseases is currently being explored. A study has revealed an association between longer telomeres obtained from leukocytes of peripheral blood and a decreased risk of mortality or dementia over a median period of 9.3 years (Honig et al. 2012). It is not certain if short telomeres are mere biomarkers of aging rather than a determinant of the aging process. If telomere length turns out to be a determinant of aging, therapies directed at modifying telomere length shortening by increasing telomerase activity may be helpful in decreasing the incidence of age-related dementia.

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