Relationship Between Neural and Chromosomal Aging

Mouse models demonstrate that reduced telomerase activity and telomere loss have widespread consequences on neurodegeneration, including restricted neurogenesis and atrophy of white matter tracts, but there is limited evidence linking TL to age-related grey and white matter deficits in humans. As a Robert Wood Johnson Foundation Health and Society Scholar (2010-2012), I began to explore the relationship between cellular and neural aging. In collaboration with Elissa Epel and Elizabeth Blackburn at UCSF and Natalie Rasgon at Stanford, we showed that cellular markers of aging reflect early structural brain changes in memory circuitry (Jacobs et al., JAMA Neurology 2014). Next, we found that APOE-ε4 (a major genetic risk factor for cognitive decline, dementia, and early mortality) is associated with accelerated cellular aging (telomere shortening) in humans. Despite the fact that the adults in our sample were currently healthy, ε4-carriers exhibited the equivalent of one decade of additional cell aging compared to non-carriers during the two-year study. Further, the data suggested that hormone therapy may buffer against cell aging in a genotype-dependent manner (Jacobs et al., Plos One 2013, Faculty of 1000 selection). 

Now, together with Jill Goldstein at Harvard Medical School, we are exploring the relationship between telomere length and grey/white matter integrity in a population-based study of midlife men and women.

This work is supported by a National Institutes of Health K12 BIRCWH Award

Learn More: 

Jacobs E.G., Epel ES, Lin J, Blackburn EH, Rasgon NL. (2014) Relationship between leukocyte telomere length, telomerase activity and hippocampal volume in early aging. JAMA Neurology. 71(7):921-923. PMCID: PMC5287208

Jacobs E.G., Kroenke C, Lin J, Epel ES, Kenna HA, Blackburn EH, Rasgon NL. (2013) Accelerated cell aging in female APOE-ε4 carriers: Implications for hormone therapy use. PLoS ONE 8(2): e54713. PMCID: PMC3572118 (Faculty of 1000 selection)