MCB 7410 Seminar | Pharmacology in Aging and Longevity: Past, Present and Future, Feb. 21

The abstract for this seminar begins with, “The quest for fountain of youth has been going on for over two millennia.” Most people are interested in the prospect of living longer and healthier, a subject Pratik Shriwas and Quyen Jason Luong will explore in their presentation “Pharmacology in Aging and Longevity: Past, Present and Future.”

Their presentation is part of MCB 7410 and is Tuesday, Feb. 21, at 4:35 p.m. in Porter 104.

Shriwas is a graduate student in Biological Sciences at Ohio University.

Refreshments are provided!

Abstract: The quest for fountain of youth has been going on for over two millennia. Different cultures from Orient and Occident have been involved in developing drugs that can increase the human lifespan. Since then, significant improvements in medical study and translational research have laid the foundation of modern anti-aging pharmacology. Currently, targeting aging is primarily dependent on our understanding of biological mechanisms at cellular level. AMPK, Insulin/IGF-1 (IIS) and mTOR signaling are the most critical intracellular signaling pathways involved in study of longevity and aging. mTOR pathway has been extensively studied at both in vitro and in vivo in S. cerevisiae, C. elegans, D. Melanogaster and M. musculus. mTOR is the master regulator of cellular metabolism and autophagy and subsequently several drugs have been developed targeting mTOR [1]. Rapamycin is the primary inhibitor of mTOR that has been extensively tested in animal models for its anti-aging properties by National Institutes of Aging’s Interventions Testing Program (ITP). Harrison et al. studied the effects of Rapamycin on genetically heterogeneous UM-HET3 mice at different ages (9 months and 20 months) and observed that the drug at 14 ppm extended the lifespan of both genders. Based on this initial research, Miller et al. expanded the study using three different doses of Rapamycin (4.7, 14 and 42 ppm). They observed that by inhibiting mTOR kinase, Rapamycin increased the median lifespan of UM-HET3 mice by 23% in males and 26% in females at the highest dosage. Females were reported to have longer lifespan than males due to sexual dimorphism of Rapamycin in blood levels. Furthermore, critical differences were seen in metabolic status as well as expression levels of xenobiotic metabolizing enzymes between Rapamycin-treated and diet-restricted mice, highlighting the presence of alternative mechanisms of action. Recently, Rapamycin has also been shown to cause hepatic insulin resistance and thereby affecting IIS pathway. Metformin, an agent that increases insulin sensitivity, was speculated to associate with increasing average human lifespan up to 120 years in the Targeting Aging using Metformin (TAME) project [4]. In the future, pharmaceuticals such as Rapamycin and Metformin could potentially be used in parallel to synergistically extend human lifespan.

1. Kennedy, Brian, and Dudley W. Lamming. “The mechanistic target of rapamycin: the grand conductor of metabolism and aging.” Cell Metabolism 23.6 (2016): 990-1003.
2. Harrison, David E., et “Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.” nature 460.7253 (2009): 392-395.
3. Miller, Richard , et al. “Rapamycin‐mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction.” Aging cell 13.3 (2014): 468-477.
4. “TAME – Targeting Aging with Metformin.” Afar(American federation for aging research). American Federation for Aging 8th February 2017. Web. 13th February 2017.