System xc- as metabolic regulator in the aging brain

Although life expectancy keeps rising, the estimated average healthy
life years is only around 64. As we age, cells of the central nervous
system gradually suffer from reduced nutrient availability as well as a
decline of metabolic functions and of mitochondrial health. These
age-related dysfunctions are associated with cognitive decline, one of
the most impactful consequences of aging. We recently observed
that absence of the cystine/glutamate antiporter system xc- increases
life span in mice and protects against age-related memory decline.
Moreover, it was shown in cancer cells that inhibition of system xcincreases
resilience to nutrient deprivation and improves
mitochondrial health. My hypothesis therefore is that the beneficial
effects of system xc- deficiency in the brain are related to an
improved cell metabolism. I will explore this by investigating the
effect of system xc- deficiency on the metabolic health of aged brain
cells at the genetic, functional, and mechanistic level. We aim to
unveil a novel strategy to counter metabolic decline in the aging
brain, and eventually to ensure healthy aging.