Doctor of Philosophy (PhD)
Aging is associated with metabolic rewiring. Most lifespan-extending longevity interventions target metabolic pathways. Genetic or pharmacological metabolic approaches that mediate longer lifespan and healthspan, are often linked to detrimental effects on human health. Here, I show that supplementation of botanical extracts from Artemisia scoparia (SCO), dramatically increases animal lifespan. Mechanistically, this lifespan extension is dependent on AMPK-DAF-16 signaling via inhibition of the insulin pathway. In SCO-fed worms, longer lifespan was accompanied by higher fat storage and improved resiliency to age-related physiological stress. Notably, DAF-16, the master regulator of longevity, activated the fatty acid desaturation processes, which promoted the accumulation of unsaturated fatty acid in the worms, following SCO administration. In line with the beneficial actions of unsaturated fatty acids in human, I show that the heightened storage of the “good fats” was necessary for the SCO-dependent extended longevity and late-age stress resistance, highlighting the positive implication of natural product intervention in animal aging and health.
Furthermore, I found that, dietary restricted conditions, one of the most common longevity interventions thus far, facilitated vesicular to tubular transformation in lysosomal morphology. Molecularly, this structural alteration required the lysosomal membrane proteins SPIN-1, SPIN-2 and SPIN-3, which were also involved in mediating the pro-longevity properties of dietary restriction. Last, I show that experimentally inducing lysosomal tubulation, even in well-fed condition, preserves health during old age, suggesting that lysosomes modulate themselves in response to the nutritional changes in the cell, possibly to meet degradative demands and that this lysosomal adaptation is linked to the longevity expansion, conferred by dietary restriction.
Altogether, my studies demonstrate that non-genetic metabolic interventions can indeed be harnessed to promote healthy aging and longer lifespan.
Ghosh, Bhaswati, "Influence of Metabolic Interventions on Animal Aging and Lifespan" (2023). LSU Doctoral Dissertations. 6092.
Available for download on Tuesday, April 14, 2026