Aging and aging-related diseases may be attributable not only to random wear and tear, but also to specific intracellular signaling pathways. We are investigating biochemical signaling pathways associated with aging-related diseases.

Targeting the biology of aging and about TORC1

Our most advanced clinical program is focused on the mechanistic target of rapamycin or mTOR. mTOR regulates the process of aging and aging-related diseases.

Inhibition of the mTOR pathway has been observed to extend lifespan and healthspan in multiple animal studies supporting the potential for drugs that target the mTOR pathway to have therapeutic benefits for aging-related diseases in humans.

mTOR is a protein that is activated by eating and inhibited by fasting. When mTOR is activated by eating, cells are stimulated to make proteins and lipids needed for growth. When mTOR is inhibited during periods of fasting, cells activate pathways that protect and repair damage in cells.

Therefore increased mTOR activity is beneficial during years of growth and reproduction, but decreased mTOR activity may be beneficial during post-reproductive years when cells accumulate damage. However, there is evidence that mTOR actually becomes hyperactive in some tissues during aging, which suggests that mTOR inhibition may be of therapeutic benefit during aging because they upregulate protective pathways.

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mTOR functions in cells within two different protein complexes called TORC1 and TORC2.

Inhibition of mTOR activity within TORC1 is associated with increased lifespan and improvement in the function of several aging organ systems, including neurologic function. In contrast, TORC2 inhibition has been observed to decrease lifespan and cause unwanted side effects like increased levels of cholesterol and glucose in blood.

We believe the optimal treatment regimen for preventing or treating aging-related diseases may be a regimen that inhibits TORC1 without inhibiting TORC2.

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