III. AGING

Role of Oxygen in Aging Physiology

Oxygen is both a necessary and toxic substrate for aerobic life, allowing for vital ATP production, while simultaneously generating damaging free radicals. Epidemiological studies suggest a close relationship between longevity and hypoxia, with 7 of the 10 longest-lived US counties found at the high altitudes of Colorado. Moreover, species that are particularly hypoxia and anoxia-tolerant (e.g. naked mole rat, African painted turtle, etc.) tend to be the longest-lived. As even more direct evidence, it was found that constitutive activation of the hypoxia transcriptional program in C. elegans increases longevity and also protects against proteotoxic stress. Thus, understanding the interplay between oxygen and the (cellular and physiological) hallmarks of aging will improve our understanding of the aging process and offer hope for new therapies for age-associated conditions.

Role of Vitamins in Aging Metabolism

The aged population is particularly susceptible to vitamin deficiencies. This can result from impaired gut absorption of micronutrients, changes in enzyme-binding affinities for cofactors and direct nutritional deficiencies. The effect of subclinical deficiencies on aging and age-associated conditions remains unknown. We aim to understand the complex interplay between different vitamins and age-associated damage.