Research Paper Outline

I.

Introduction a. Thesis – Telomeres and mitochondria play a critical role in cellular senescence, and are functionally interrelated at multiple levels.

II.

Theories of Aging a. Mitochondrial Damage i. ROS production ii. Decreased respiratory capacity b. Cellular Senescence i. Telomeres 1. Hayflick limit ii. Telomerase

III.

A connection between Mitochondria and Senescence a. Mitochondrial dysfunction & shortened telomeres b. Mitochondrial-nuclear cross-talk i. Retrograde response 1. PGC-1α 2. calcium signaling c. UCPs as an adaptive mechanism to reduce ROS

IV.

Current Research a. Telomerase deficiency promotes oxidative stress by reducing catalase activity b. Mitochondrial TERT binds & protects mtDNA c. Mitochondrial dysfunction results in uncapped telomeres d. hTERT is associated with diminished mtDNA damage e. Telomerase protects mitochondrial function

V.

Conclusions a. The predominant mediators of cellular senescence are telomeres and mitochondria, both of which have relatively unprotected DNA and are likely targets of oxidative damage.