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.