Modulating diet and mitochondria to promote longevity

Aging is broadly defined as the time-dependent loss of functional integrity accompanied by increasing vulnerability to death with advancing age. Within the last century, improvements in health care and the discovery of antibiotics have profoundly increased human lifespan expectancy, but the age of the onset of many diseases has not been delayed significantly. Older age—generally over 65—is associated with higher risks of developing the diseases such as cancer, cardiovascular disease, diabetes, stroke, chronic inflammation, and various neurodegenerative diseases. Understanding the mechanisms underlying aging process is central to combat physiological changes that result in morbidity and mortality. Much of our understanding of the genetic basis of aging derives from studies leveraging short-lived model organisms such as yeast, worms and flies. For example, the role of nutrient sensing pathways and mitochondrial stress signaling pathways in modulating aging have been most extensively studied in worms. In addition to genetic factors, environmental signals such as exercise and diets also affect the trajectory of aging. This thesis aimed to achieve three major goals: (1) to gain more insights into the interplay between mitochondrial morphology and mitochondrial function in regulating lifespan; (2) to investigate the effects and underlying mechanisms of glycine on lifespan; (3) to search for novel factors that modulate lifespan in response to a fat diet.