CANCER AS A PART OF AGING

1. The Connection Between Cancer and Aging

Data on cancer indicates a direct correlation with aging. In countries with aging populations, cancer incidence is significantly higher than in younger populations. While age-adjusted incidence rates vary significantly between countries, possibly due to early detection, age-adjusted cancer mortality rates are relatively uniform worldwide, with most countries reporting 80 to 100 deaths per 100,000 people. This suggests that cancer is primarily related to aging.

If we consider cancer and aging as two types of diseases, we see many similarities between them, showing a strong equivalence. Researchers have identified common features such as genomic instability, epigenetic alterations, chronic inflammation, and dysbiosis as hallmarks of both aging and cancer. Some hallmarks of aging, such as loss of proteostasis, mitochondrial dysfunction, and altered intercellular communication, do not have direct counterparts in cancer markers but may contribute to specific cancer characteristics, thereby facilitating resistance to cell death, glycolytic metabolism, and tissue structure disruption.

Other aging hallmarks, like telomere attrition and stem cell exhaustion, clearly inhibit specific aspects of tumor development, such as replicative immortality and phenotypic plasticity. These are considered antagonistic hallmarks because they may represent instances of antagonistic pleiotropy. Dysfunctional autophagy and cellular senescence, two other hallmarks of aging, have context-dependent tumor-suppressive and tumor-promoting roles and thus warrant separate discussion. Additionally, the equivalence or antagonism between aging-related nutrient sensing dysregulation and cancer-related metabolic disturbances is complex, necessitating research into the shared metabolic features of aging and cancer.

The failure of cancer immunosurveillance may be influenced by several aging characteristics. If this book compares cancer and aging, it might seem irrelevant to someone with cancer. However, understanding every relationship between aging and cancer could be crucial for someone who has cancer.

We need to carefully consider whether aging is a disease. Clearly, it is not; it is a natural law that everyone will experience. From the perspective of first principles, aging is a fundamental law that cannot and need not be broken down; it is not a problem but an axiom. On the other hand, cancer is a disease. Everyone ages, but not everyone develops cancer.

Human aging manifests uniformly: cellular senescence, tissue deformation, and organ dysfunction. Cancer also involves abnormal cell proliferation, tissue deformation, and organ dysfunction. Since aging encompasses more than cancer, we should not view them as two distinct diseases; rather, aging includes cancer, or cancer is a part of aging.

Given the current limitations of cancer treatments, which prevent cancer from becoming a chronic, manageable condition like an aging-related disease, if we view cancer as a part of aging, there should be therapies or drugs that can treat both cancer and counteract aging. Indeed, such a drug exists: metformin. Extensive clinical data has proven that metformin has low side effects and possesses both anticancer and anti-aging properties.

2. Cancer and Aging in the Life model

In our life model, aging is seen as the natural accumulation of senescent cells. When a certain proportion of these cells accumulates, it leads to the end of an individual's life. Some organs may have a higher proportion of these aged cells, indicating they have aged more significantly. Senescent cells are defined by their abnormal structure, diminished function, and their long-term occupation of space that could otherwise be occupied by new, healthy cells.

If we extend this definition to include cells that not only have an abnormal structure and completely lost function but also occupy space long-term without making way for new, healthy cells, and progressively destroy the surrounding tissue structure through proliferation, we describe the characteristics of cancer cells. Although cancer cells and senescent cells are not entirely the same, in our life model, they are indistinguishable to some extent. This means our life model can describe both the aging process and the cancer process.

In the Further Readingsection of this book, readers with a mathematical background will find that our life model primarily describes the quantity of senescent cells, including typical chronic disease-damaged cells and cancer cells. This implies that treatment variables in our life model mainly involve the clearance of senescent cells. We know that merely clearing damaged cells does not complete the treatment process, as the cleared cells leave behind physical space. Fortunately, organisms have an innate regenerative ability; once some cells are cleared, the organism automatically regenerates healthy cells to fill these spaces, a process that occurs without human intervention. Therefore, our life model is comprehensive, whether addressing aging or cancer.

For aging, the theoretical approach to anti-aging involves selectively clearing senescent cells. Effective methods include new therapies that directly clear these cells, reducing their proportion, or by stimulating the immune system to recognize and clear them. Selective clearance of senescent cells has become a hot topic in medical research and has shown promising results in animal studies.

For cancer, the treatment approach also involves selectively clearing cancer cells. Methods for clearing cancer cells include direct removal through surgery or ablation, or by stimulating the immune system to recognize and clear them. Nearly all cancer therapies currently employ one or a combination of these approaches.

Thus, our life model is fundamentally correct in describing both aging and cancer.

Considering metformin, which can both fight cancer and counteract aging, its ability to achieve these effects with minimal side effects primarily lies in its capacity to utilize the body's ROS to clear both senescent and cancer cells. Research indicates that metformin's benefits extend beyond traditional treatments, including weight loss, cancer prevention, anti-aging, anti-inflammatory effects, and even antiviral responses. While there is some controversy, some reports suggest that metformin may increase ROS levels, which could potentially trigger systemic anti-tumor immune responses and promote tissue regeneration. This hypothesis suggests that metformin's mechanism in treating various diseases might involve using ROS to clear damaged cells, contributing to its anti-aging and anti-cancer effects.

3. Insights from Anti-Aging Strategies for Cancer Treatment

Compared to cancer treatment, anti-aging is not as urgent, and because it involves longer clinical trials, there are not as many new therapies for anti-aging as there are for cancer treatment. Anti-aging focuses on the long term and rarely encounters common issues in cancer treatment such as treatment choice dilemmas and overtreatment. Given this, the few anti-aging approaches that align with first principles may offer insights for cancer treatment.

Currently, the focus in anti-aging is on a type of drug known as senolytics. These drugs can selectively clear senescent cells and have shown promising anti-aging effects in animal studies, with apparently low long-term side effects. Clearing senescent cells has gradually become a main focus in the development of anti-aging drugs.

Observing the development of senolytics as anti-aging agents offers several lessons for cancer treatment:

1)      Effectively clearing cancer cells is key to fighting cancer, but aiming for 100% clearance is not necessary. As technology advances, our ability to identify and clear cancer cells will improve. However, since aging is inevitable, it is unlikely that all senescent cells can be cleared in the pursuit of anti-aging. In contrast, current cancer treatments often aim for 100% clearance of cancer cells, which is technically unfeasible and can lead to overtreatment.

2)      Transforming cancer into a chronic condition, similar to anti-aging, suggests that cancer treatment should also be continuous. Just as we accept that senescent cells cannot be completely cleared at once and will accumulate over time, anti-aging measures are used continuously. In cancer treatment, both doctors and patients often aim for a one-time clearance of cancer cells, hoping they never return, which mirrors the first point. Our life model assumes that if the accumulation of senescent cells (or cancer cells) is kept at a low level, the organism can still survive, much like aging. Living with cancer is a more achievable treatment goal in reality.

3)      The goal of treatment should be long-term high-quality life. Anti-aging aims to enable people to continue living high-quality lives. However, the goals of cancer treatment are often short-term. In choosing treatment methods, doctors might first aim to clear cancer cells completely; second, try to prevent recurrence, which severely opposes the concept of living with cancer; and third, completely disregard the patient's quality of life post-treatment. If the goal of cancer treatment is set on long-term high-quality life, most overtreatment can be avoided. Patients who read this book should aim for a long-term high-quality life as their goal for cancer treatment, using first principles to choose appropriate treatment methods and influence doctors' decisions, which I believe can maximize treatment effectiveness.

4)      More attention needs to be paid to side effects in cancer treatment decisions. Since anti-aging targets long-term high-quality life, any promising anti-aging therapy must be closely scrutinized for side effects, even minor ones, which could lead to the therapy being rejected. This is why the anti-aging industry is filled with a multitude of supplements that are explicitly free of side effects. In contrast, many cancer treatments involve toxic drugs and various cell-damaging therapies. While these are necessary to clear cancer cells, the side effects, which can harm the whole body or immune system, are often overlooked, resulting in treatments that sacrifice long-term quality of life for immediate effects.

5)      Drugs that can counteract aging are likely to have anti-cancer effects. Conversely, if a cancer treatment does not have anti-aging effects, it should be carefully considered by patients, as it might be an inappropriate method. Although senolytics, drugs that selectively clear senescent cells, are not yet approved, many researchers have incorporated them into the development of anti-cancer drugs, indicating a general consensus that anti-aging drugs are likely to be effective against cancer. In the development of new cancer drugs, regardless of the inefficiency of traditional cancer drug development and the fact that existing cancer drugs may not provide long-term benefits, you do not need to wait for better, first-principle-aligned cancer treatments. You can use metformin for cancer treatment, as extensive clinical data shows it can both counteract aging and fight cancer.

I recommend considering metformin for several compelling reasons:

Firstly, a wealth of research and clinical experience has shown that metformin can effectively eliminate abnormal cells, boost tissue regeneration, and adjust immune responses. This occurs through its ability to produce reactive oxygen species (ROS) at the cellular level, similar to the action seen in anti-tumor immune responses.

Secondly, using metformin off-label for non-diabetic conditions is both legally acceptable and generally safe.

Thirdly, metformin is well-tolerated by most individuals, with mild diarrhea being the most frequent side effect.

Additionally, metformin has been found to offer various health benefits, including weight loss, life extension, cancer inhibition, and anti-inflammatory effects. These serendipitous benefits are akin to those observed with chlorine dioxide. Unlike some targeted cancer therapies, which can lead to resistance, metformin can be safely used over a long period.

Lastly, metformin is a cost-effective option, enhancing its accessibility for broader use.