The Role of Sirolimus in Preventing Functional Decline in Older Adults
Status:
Not yet recruiting
Trial end date:
2025-09-01
Target enrollment:
Participant gender:
Summary
Aging is associated with progressive impairment of tissue and organ function, resulting in
increased susceptibility to chronic disease, frailty and disability. Currently there are
limited treatment options to alter this inevitable process. The proposed work has the
potential to identify a new therapeutic intervention to decrease aging-related degenerative
processes.
Rapamycin or sirolimus is a macrocyclic immunosuppressive drug that inhibits the mammalian
target of rapamycin (mTOR). The mammalian target of rapamycin (mTOR) pathway is part of
phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin
(mTOR)-dependent pathway which is a fundamentally linked to cell metabolism, proliferation,
differentiation, and survival (1). This pathway is altered in a variety of diseases,
including cancers, immunosuppressed states, and fibroproliferative diseases. The mTOR kinase
is considered one of the leading regulators of this pathway. Changes in mTOR signaling are
closely associated with inflammation, cell growth and survival, leading to the development of
chronic diseases (2). Recent evidence also suggests that mTOR inhibitors are promising
modulators of the aging process by slowing the mechanisms of aging at the cellular level (3).
There is a growing appreciation of the potential impact of sirolimus in slowing aging
processes and in prolonging healthy lifespan.
The proposed study addresses critical gaps in our understanding of the safety and efficacy of
sirolimus in delaying aging processes and is based on findings in animal studies and
incidental clinical observations. We will overcome potential biases with a randomized control
trial. The proposed intervention study is intended to improve our insight into clinical
outcomes leading to prevention of chronic diseases such as skin cancer and mortality. Our
overarching hypothesis is that sirolimus is one of the first pharmacological agents that will
impact the aging process and chronic disease development. Specifically, we aim to investigate
whether sirolimus can reduce the occurrence or increase in biomarkers of aging processes.