Inhibition of PDK1 Can Reverse Cell Aging

Inhibition of PDK1 Can Reverse Cell Aging

Posted by Valerie Walters on Dec 4, 2020 1:47 pm

Recent studies showed that cellular senescence, previously considered an irreversible biological phenomenon, may represent a reversible state, but the mechanism for the reversion is not well elucidated. Last month, Research findings by a Korean team provide insight into the complex mechanism of cellular senescence and present a potential therapeutic strategy for reducing age-related diseases associated with the accumulation of senescent cells.

To identify targets the inhibition of which would convert senescent cells into quiescent cells, the researchers constructed a molecular regulatory network model of cellular senescence. From ensemble analysis of network models, they identified 3-phosphoinositide–dependent protein kinase 1 (PDK1) as a promising target for inhibitors to convert the senescent state to the quiescent state. The researchers validated this prediction in experiments with human dermal fibroblasts, which showed that PDK1 inhibition eradicates senescence hallmarks by suppressing both nuclear factor κB and mTOR signaling through the inactivation of a positive feedback loop composed of PDK1, AKT, IKBKB, and PTEN, resulting in restored skin regeneration capacity. The findings were published in the Proceedings of the National Academy of Sciences.

PDPK1 is a master kinase, which is crucial for the activation of AKT/PKB and many other AGC kinases including PKC, S6K, SGK. An important role for PDPK1 is in the signaling pathways activated by several growth factors and hormones including insulin signaling.

"Our research opens the door for a new generation that perceives aging as a reversible biological phenomenon," says Professor Kwang-Hyun Cho of the Department of Bio and Brain Engineering at the Korea Advanced Institute of Science and Technology (KAIST), who led the research with colleagues from KAIST and Amorepacific Corporation in Korea. The scientists recommend investigations are next done in organs and organisms to determine the full effect of PDK1 inhibition. Since the gene that codes for PDK1 is overexpressed in some cancers, the scientists expect that inhibiting it will have both anti-aging and anti-cancer effects.

"The study showed the potential for reverse the aging process, which has been recognized as an irreversible phenomenon in life," Professor Cho said. "This research marked the beginning of a new era that can prevent diseases related to aging and prolong life span."

PDK1 inhibitors that are currently available

Compound More information

Re: Inhibition of PDK1 Can Reverse Cell Aging

Posted by Mark Garcia on Dec 26, 2020 1:58 pm

How cool is it that they are near making anti-aging creams? I want to be just like the scientists and for that, I need to and study hard. I know I can reach their level if I focus enough.

Re: Inhibition of PDK1 Can Reverse Cell Aging

Posted by Phill Wagner on Feb 10, 2021 2:53 pm

This is what we are like. Collectively as a species, this is our emotional landscape. I met an old lady once, almost 100 years old, and she told me, "There are only two questions that human beings  have ever fought over, all through history. How much do you love me? 

Re: Inhibition of PDK1 Can Reverse Cell Aging

Posted by Phill Wagner on Feb 16, 2021 3:04 pm

 It is the slow drip that creates the stalactite, the shaking of the Earth that creates mountains, the constant pounding of the waves that breaks up the rocks and smooths the rough edges. 

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