Frida Matiyevskaya

Aging is the most significant risk factor for multitude of diseases, encompassing diabetes, cancer, cardiovascular conditions, and neurodegenerative disorders. What causes aging is unknown, but likely multifactorial. A prominent idea is the damage accumulation theory of aging. Our cells are constantly bombarded by endogenous and exogenous agents that damage our genome. Interestingly, it has been shown that activation of DNA repair protein PARP1 increases with age and in disorders of accelerated aging. Hyperactivation of PARP1 appears to lead to NAD⁺ loss and consequently downstream pleiotropic mitochondrial dysfunction and metabolic derangement. Furthermore, it has been shown that NAD⁺ levels decrease with chronological aging across multiple species. However, given the steady state nature of biochemical reactions and the very slow accumulation of damage over time it is unclear how a persistent DNA damage response can alter the biochemical equilibrium leading to less NAD⁺.
In my PhD project I aim to address the interplay between PARP1 and NAD⁺metabolism in relation to aging.