Mikhail Blagosklonny’s theory of cellular hyperfunction has shifted our understanding of aging by proposing that it’s not a result of cellular decline or damage accumulation but rather an overactive state of cellular metabolism. One of the most infamous examples of this is cancer.
In a recent research perspective article, Blagosklonny outlined the role of rapamycin in slowing both the progression and delaying the onset of cancer.
In this week’s Healthspan Research Review, Jacob Rose, from the Buck Institute for Aging Research, discusses the multiple mechanisms of rapamycin that impede cancer development and formation.
We investigate the part played by cellular senescence in shaping a microenvironment that facilitates aggressive cancer growth. In our analysis, we evaluate the influence of rapamycin on senescent cells and its potential to amplify the immune system’s defensive response to cancer cells.
Here is the full article:
Here is a breakdown of the articles mainpoints:
Dr. Mikhail Blagosklonny’s “Hyperfunction Theory of Aging”:
Aging phenotypes are linked to cellular hyperactivity, leading to excessive growth and proliferation, similar to cancer hallmarks.
mTOR: Master Growth-Regulating Complex:
mTOR is a crucial nutrient-sensing complex in cells, and its overactivity is associated with cancer development.
Drugs like rapamycin inhibit mTOR, directly targeting Blagosklonny’s theory of aging.
mTOR Inhibitors in Cancer Treatment and Prevention:
Preclinical mouse models showed mTOR inhibitors slow cancer progression at all stages, regardless of treatment initiation.
High-risk individuals might benefit from mTOR inhibitors as a preventive measure to delay cancer onset.
Limited Cure Potential, but Prolonged Cancer-Free Time:
Rapalogs, like rapamycin, may not cure cancer but can significantly slow its progression.
High-risk patients can gain more cancer-free time through this approach, complementing other cancer treatments.
Clinical Data Supports mTOR Inhibitors:
mTOR inhibitors, including rapamycin, are used in humans as mild immunosuppressants for transplant patients.
Transplant patients on mTOR inhibitors show a lower incidence of cancer compared to non-users.
Targeting mTOR Signaling in Cancer:
Over 70% of cancers exhibit overactive mTOR signaling.
mTOR inhibitors disrupt this pathway, potentially slowing or stopping cancer cell proliferation and promoting apoptosis.
mTOR Inhibitors and Anti-Aging Effects:
Rapamycin and rapalogs display robust anti-aging effects, lowering the risk of age-related diseases, including cancer.
Reducing Harmful Senescent Cells:
mTOR inhibitors can reduce the accumulation of senescent cells, which cause chronic inflammation and increase cancer risk.
By inhibiting mTOR, rapamycin reduces the toxicity of the senescence-associated secretory phenotype (SASP), promoting tumor growth.
Multi-Faceted Impact on Senescent Cells:
mTOR inhibitors hinder senescent cells’ harmful effects through mechanisms like protein synthesis inhibition, autophagy promotion, and cell cycle arrest.
Rapamycin seems to increase immune function and capacity for immune system to target cancer cells.
Is rapamycin in either oral or topical form suitable for somebody who has squamous skin cell carcinoma?
I’ve seen literature that suggests rapamycin can help treat esophageal squamous skin cell carcinoma but I’ve yet to find an article where rapamycin has been used to treat face & head squamous skin cell carcinoma.
I did come across a comment somewhere on this platform that rapamycin can cause cancer, however, if I am interpreting the research properly, it seems that per the studies, the increased risk of cancer while using rapamycin was seen in people who have undergone an organ transplant.
This leads me to speculate that those individuals developing cancer would have likely developed cancer regardless of whether or not they were using rapamycin and not as a result of using rapamycin. Is this accurate?
Could you please shed some light on this? Thank you!
Hello! This is Brandon from the Healthspan Clinical Team. Thank you so much for posting this question; we love to dive deep into emerging research. Our physician-led team has a data-driven policy to address individual protocols, as each person’s health history, diagnosis, and even geographic location (which matters!) are different. While no human data is available for every diagnosis, we can offer this physician-led understanding of how all of our bodies operate, which is manipulated by a deep understanding of how oral rapamycin works physiologically. Given the complexity of this condition, we relish the opportunity to be included as part of the oncology care team to serve this type of patient best, communicating lab results and subjective feedback specific to each person’s health journey. The paramount part is understanding that each cancer and the tissue it affects is different. For example, breast cancer, pancreatic cancer and skin cancer are not the same, and the metabolism each of these cells utilize is not uniform. Some prefer glucose, (breast cancer), while others grapple for anything available (pancreatic). While Otto Warburg’s theory has big picture merit in terms of cellular metabolism, there is not a one-size-fits-all approach. Speaking specifically of squamous cancer, rapamycin may have positive impacts on this condition by increasing cellular autophagy and slowing cellular senescence. Additionally, low-dose rapamycin targets the mTOR pathway, which plays a critical role in cell growth and proliferation, including cancer cells. By inhibiting this pathway, rapamycin may help slow the growth of basal cell carcinoma and reduce tumor progression.
There is a ‘same but different’ mechanism of action for topical versus oral rapamycin ingestion. By inhibiting mTOR via oral rapamycin, we are providing a press-pulse mechanism on the anabolic aspects of this pathway. Cancer cells love to grow (anabolism, metastases), and usually thrive in the presence of processed foods, high glycemic foods, and circuitously, insulin elevation (which in its own is also an anabolic hormone!). Oral rapamycin acts systemically, while topical rapamycin acts locally. Both are wins. It would be impossible to say whether an individual would have developed cancer or not without a lifetime of lab data, nutrition data, lifestyle data, and geographic location. Sometimes, people are dealt a genetically unfortunate hand and that stinks. It would be similar to me asking how many times you got sick over the last decade while talking an MVI or Vitamin C supplement. Did it help? Maybe. Did it hurt? Probably not. If you are able to connect with us and monitor your health in a continual manner, we can piece together all facets of your health and holistically move things forward, to match what longevity means to you.