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Clinical implications for mitochondrial stress induced senescence and potential interventions
Dissertation   Open access

Clinical implications for mitochondrial stress induced senescence and potential interventions

Ashley Zarify Azar
Doctor of Philosophy (Ph.D.), Drexel University
Aug 2017
DOI:
https://doi.org/10.17918/etd-7583
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Abstract

Medical sciences HIV infections Mitochondria Older people--Diseases Aging Genomics
Understanding the mechanisms behind how cells and organisms age is of great importance when trying to develop therapies to combat multiple age-related disorders without the need for excessive prescription medications. One context where age related disorders are prevalent is in patients suffering from HIV-1 infection. These patients, even when on antiretroviral therapies, exhibit multiple signs of premature aging, one of which includes HIV-associated neurocognitive decline. Deficits in these patients are thought to be due to a combination of viral infection and long-term antiretroviral treatment. Antiretroviral drugs are known to induce mitochondrial damage, which may be responsible for driving comorbidities in this population. Further analysis of the impact of drugs on mitochondria is required to fully elucidate toxicity and develop adjuvant therapies. In addition, these patients exhibit a large degree of heterogeneity in the severity of side effects that is still not well understood. In order to understand these dynamic interactions, we set out to determine if mitochondrial genetic backgrounds can influence neurocognitive heterogeneity, determine the mitochondrial and cellular effect of antiretrovirals and identify potential therapeutics that can help combat cellular dysfunction and provide relief for patients suffering from age related diseases.

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