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Want to live longer—get skinny and find some young blood!

As I age I get more interested in the science of longevity.   However, like blockchain there are more lies than there are truths and the internet is filled with the promotion of quackery.   There are however several areas of promising research.   As I build my research I will keep these notes updated on the subject.

1.      Parabiosis-Replacing old blood with young blood


Several years ago, researchers found that there were compounds in the blood of young mice that could awaken old stem cells and rejuvenate aging tissue in old mice.   The researchers focused on a protein called GDF11 and found that it revived stem cells in old muscles, making old mice stronger and increasing their endurance.  It also looked like the blood of young mice altered the brains of old mice with new neurons in the hippocampus (a region of the brain that is crucial for forming memories) and also spurred the growth of blood vessels in the brain.  Researchers also found that by injecting GDF11 alone into mice had an impact, although the change was not as large as that from parabiosis.

Later research found that the enzyme Tet2 (ten eleven translocation methylcytosine dioxygenase 2), a known regulator of gene activity linked to several age-related diseases, was responsible for the enhanced cognitive functions in the adult mouse brains.  It seems that some circulating factor in the blood was able to change the level of Tet2 in the brain.

There is still a lot of research required given some caution that waking up stem cells might also lead to them multiplying uncontrollably.


2.      Caloric Restriction

Undernutrition without malnutrition has been found to be one of the most successful approaches to life extension in laboratory settings. Researchers have been able to extend the mean and maximum lifespan of laboratory rats by 40% or more.  It is theorized that the longevity extension has to do with an activation of survival mechanisms that have been evolutionarily conserved to protect an organism from stress. A small human study of 60 healthy seniors receiving an average of 1500 kcal/day for a period of 3 years found significantly lowered rates of hospital admissions and a numerically lowered death rate than an equal number of control volunteers.

The downside of caloric restriction in senior citizens relates to decreases in muscle mass, strength, aerobic capacity and bone mineral density.

3.      Gene Therapy

Mitochondria serve a variety of critical functions within the cell including supplying cellular energy, cell signaling (communication process that governs basic activities of cells and coordinates all cell actions) and metabolism (conversion of food/fuel to energy to run cellular processes, the conversion of food/fuel to building blocks for proteins, lipids, nucleic acids, and some carbohydrates, and the elimination of nitrogenous wastes.). However, a mild disruption of the mitochondrial function has been shown to increase lifespan.   It is theorized that by manipulating insulin metabolism (such as through the development of calorie restriction mimetic drugs) may modestly slow down aging.  This has to do with two hormone receptors–the receptors for insulin and IGF-1 (these receptors signal the uptake of energy and growth).  Drosophila melanogaster3 (a mutation in the gene that encodes the insulin/IGF-1 receptor) results in higher longevity.

4.      Drug: Rapamycin, an immunosuppressant and anti-cancer drug

The Navartis drug Rapamycin has been shown to extend lifespan in mice.  The drug is a biological agent discovered in the soil on Easter Island.

5.      Drug: Metformin

Metformin is an old generic diabetes drug known for its blood sugar lowering properties and for being quite safe and has been found to stall the aging process in animal studies.

6. Drug: RAD001 and BEZ235, cancer drugs

RAD001 is used to fight cancer and prevent rejection in organ transplant patients. The other, known as BEZ235, was developed as a cancer drug. Both drugs, known as TORC1 inhibitors, affect a crucial cellular pathway that plays a role in the immune system and other biological functions. Similar drugs were previously linked to extending the lifespans of lab animals. 


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