Outlive: The Science and Art of Longevity

In Chapter 8, Attia argues for a three-part strategy for dealing with cancer. The first strategy is to avoid getting cancer. Cancer prevention is tricky, since the medical field lacks a basic understanding of the origin and progression of many cancer types compared to the other Horsemen diseases. Bad luck also plays a role in the form of cell mutations (which we cannot control). However, Attia believes an essential strategy is “getting our metabolic health in order” (154). People need to address obesity, insulin resistance, and type 2 diabetes, all of which are metabolic dysfunctions that drive cancer growth.

The second strategy is to use “newer and smarter treatments targeting cancer’s manifold weaknesses” (145). Traditionally, oncologists use chemotherapy to treat cancer. Chemotherapy, unfortunately, kills both cancerous cells as well as normal healthy ones. Insatiable metabolic hunger is one weakness of cancer cells. Researchers are trying to target cancer metabolism to create more effective cancer treatments. PI3K inhibitors are one class of drugs doing exactly this, although their success rate has not been as high as hoped. Dietary interventions including fasting or fasting-like diets might make both PI3K and chemotherapy more effective since they help starve cancer cells. Recent research suggests that we need to use a combination of different therapies to attack cancer.

The second weakness of cancer cells is that they are vulnerable to immune-based therapies. Attia defines immunotherapy as “any therapy that tries to boost or harness the patient’s immune system to fight an infection or other condition” (158). It has been difficult to get the immune system to fight against cancer, since technically cancer cells are part of us. T cells, which the immune system uses to kill foreign cells, do not recognize cancer cells as foreign. Thus, for cancer immunotherapy to work, we need “to teach the immune system to recognize and kill our own cells that have turned cancerous” (158). After years of research, we have started to create immunotherapies, including chimeric antigen receptor T cells (CAR-T), checkpoint inhibitors, and adoptive cell therapy, that successfully target certain kinds of cancer. A striking feature of immunotherapy is that if patients respond, they often stay in remission (whereas chemotherapy patients rarely stay in remission for long).

The third strategy is to try and detect cancer as early as possible. Attia advocates for “early, aggressive, and broad screening” (145). It is much easier to treat cancer in its early stages when tumors have fewer mutations than in the later stages when these mutations have advanced and are often resistant to cancer treatments. Early screening does come with financial and emotional costs and incidental risks, but Attia believes the cost of missing cancer far outweighs these three costs.

Attia notes that “Alzheimer’s disease is perhaps the most difficult, most intractable of the Horsemen diseases” (179). While there are other neurogenerative diseases, Attia focuses on Alzheimer’s disease because it is the most common. The apolipoprotein E (APOE) gene, which “is involved in cholesterol transport and processing” (67), influences the risk of Alzheimer’s. APOE has three variants: e2, e3, and e4. APOE e3 is the most common variant. APOE e4 is the most concerning variant, since having one or two copies significantly increases the risk of a person developing Alzheimer’s disease.

German psychiatrist Dr. Alois Alzheimer was the first to discover Alzheimer’s disease while conducting an autopsy on Auguste Deter, a woman in her mid-fifties. Auguste had experienced a cognitive condition in her final years. While it took researchers over 50 years to accept that “‘senile dementia’ was a disease state and not just normal consequences of aging” (181), research for many years was based on this initial discovery. Specifically, researchers believed that the number of plaques, which contain a peptide called amyloid-beta, found within the brain correlates with a patient’s degree of cognitive impairment. Dr. Alzheimer found these plaques in Auguste’s brain.

Amyloid-beta accumulation is bad news since it impairs cognitive function and triggers the accumulation of a protein called tau. Tau causes neuronal inflammation, which leads to brain shrinkage. For these reasons, researchers suspected that amyloid-beta accumulation was the primary driver of Alzheimer’s disease. Researchers developed drugs to target amyloid-beta, but all of them have failed to improve cognitive function or slow the progression of Alzheimer’s disease. These failures led researchers to conclude that their index case for Alzheimer’s disease, which was Auguste, had a version of the disease that only comes from having the APOE e4 variant.

Attia discusses whether we can prevent Alzheimer’s disease. Like the other Horsemen diseases, “dementia has an extremely long prologue” (189), which researchers are just starting to document. Dementia can progress for years without any outward symptoms. However, having a robust cognitive reserve might be one prevention strategy. Education, curiosity, and exercise help build and maintain cognitive reserve.

Attia also believes examining Alzheimer’s disease separately from the amyloid-beta theory offers prevention opportunities. One alternate theory is that problems with cerebral blood flow (called perfusion) increase Alzheimer’s risk. Studies on rats, evidence from people who have had strokes or a history of cardiovascular disease, and improved neuroimaging techniques have confirmed reduced blood flow as one driver. Robust blood flow and, thus, good vascular health maintain brain health.

Another theory is that abnormal glucose metabolism in the brain increases the risk of Alzheimer’s. Metabolic dysfunction massively increases a person’s risk of developing this disease. Insulin helps with memory function. Insulin resistance thus blocks this ability and appears to be another driver for the development of Alzheimer’s disease.

APOE e4 seems to accelerate these and other risk factors associated with Alzheimer's disease. One neuroscientist notes that “people with the e4 allele appear to have defects in both cholesterol transport and glucose metabolism, to a degree not seen in those with e2 or e3” (198). Thus, APOE e4 seems to drive metabolic dysfunction. For this reason, Attia argues that people need to pay attention once again to their metabolic health as one prevention tool against Alzheimer’s disease.

Diet, exercise (including strength training), sleep, use of dry saunas, and oral health (all examples of Medicine 3.0) appear to be important ways we can improve metabolic, heart, and brain health and reduce the risk of Alzheimer’s.