Anti-Aging Remedies - Metformin and Rapamycin

 

There are twelve hallmarks of aging – cell-based changes that explain how we break down with age. In an article by Chen et al. in GEN Biotechnology is a description of how Metformin, an medicinal herb first discovered in the French lilac in 1653, slows aging by targeting at least nine of the hallmarks of aging. Key is one central pathway that enables metformin's anti-aging superpower: AMPK activation.

In the seventeenth century, Metformin was used to treat things like worms and pestilence, and then later was found to lower blood sugar in people with diabetes. Today it is one of the most widely used drugs in the world in the treatment of type 2 diabetes.

Rapamycin is a molecule made by the bacterium Streptomyces hydroscopicus, discovered on Easter Island in 1972. It got its name from the original name for Easter Island – Rapa Nui; the mycin part comes from its originally discovered role as an antifungal agent. Available only by prescription, the FDA approved it to prevent kidney transplant rejections, for treating a lung disease called LAM, and for treating angiofibromas, facial bumps that can occur in people with a condition called tuberous sclerosis.

While originally characterized as an immunosuppressant, it seems to act more as an immune modulator, meaning it helps our immune system behave the way it should, without over- or under-reacting. It also helps fibrotic cells from proliferating, preventing damaging scarring of the lungs, which explains its anti-cancer properties. Rapamycin's immune-modulating and anti-proliferative effects are due to its role as an mTOR inhibitor, and this is where its longevity potential comes into play.

mTOR is one of the pathways of longevity, short for mammalian Target Of Rapamycin. mTOR encourages cells to get out of control; rapamycin reigns them back into control, so mTOR is what rapamycin targets.

AMPK stands for adenosine monophosphate-activated protein kinase, and serves as an outstanding energy sensor for our cells. When our cells lack energy, it is AMPK that ramps up the energy to levels we need. When our cells lose control, it is AMPK that brings mTOR back into line. Both Rapamycin and Metformin activate AMPK, resulting in controlled inflammation, lowered oxidative stress, and an overall balance at the cellular level with appropriate maintenance and repair. As we age, unfortunately, this pathway starts to glitch as our cells, bodies, and brains begin to falter. Consequently, our immunity, organ function, and gut health get thrown out of balance.

When we think of aging we generally think of slowing down, however, paradoxically our cells may in fact be speeding up. In the journal Cell Cycle Blagosklanny describes how our cells hyperfunction as we age. Think about it! Hypertension, hypercholesterolemia, system-wide inflammation, and overgrowth of cells that cause cancer... all hyperfunction! Hyperfunction in any form is the result of growth-promoting pathways, including mTOR and AMPK. If we can moderate these pathways with calming compounds such as Metformin, Rapamycin, and C15:0, we improve the odds of delaying aging.

Metformin and Rapamycin amplify AMPK, much the same as the fatty acid C15:0. While these compounds happen to target our key longevity pathways, one must wonder which molecules in our bodies are supposed to be keeping our longevity pathways in optimal shape? Certainly these pathways aren't just lying dormant waiting for us to supplement with these discoveries. A reasonable hypothesis is that while C15:0 is commonly found in small amounts in many foods, we may still not be getting adequate amounts in our modern diet. Supplementation with just a small amount daily may make all the difference in restoring balance at the cellular level.

When our C15:0 levels are low, either due to advancing age or nutritional deficiency, cellular health is compromised and we age more quickly. Anything that amplifies AMPK should restore cellular integrity and delay aging.

extracted from emails from info@fatty.com on July 28, and August 4, 2024

The 12 Hallmarks of Aging

• Genomic instability: Accumulation of DNA damage and mutations, leading to errors in DNA replication and repair, increasing the risk of cancer and other age-related diseases.

• Telomere shortening: Gradual shortening of telomeres with each cell division, eventually leading to cellular senescence or apoptosis (programmed cell death).

• Epigenetic alterations: Changes in gene expression and chromatin structure, influencing cellular behavior and contributing to age-related diseases.

• Loss of proteostasis: Impaired ability to maintain protein homeostasis, leading to protein misfolding, aggregation, and cellular stress.

• Deregulated nutrient sensing: Disrupted ability to detect and respond to nutrients, contributing to metabolic dysfunction and age-related diseases.

• Mitochondrial dysfunction: Decline in mitochondrial function and efficiency, leading to reduced energy production and increased oxidative stress.

• Cellular senescence: Permanent cell cycle arrest, often in response to stress or DNA damage, contributing to tissue dysfunction and age-related diseases.

• Stem cell exhaustion: Decline in stem cell function and number, impairing tissue regeneration and repair.

• Epigenetic drift: Gradual changes in epigenetic marks over time, influencing gene expression and contributing to age-related diseases.

• Disrupted autophagy: Impaired ability to recycle damaged cellular components, leading to accumulation of waste and potentially contributing to age-related diseases.

• Chronic inflammation: Persistent low-grade inflammation, contributing to tissue damage and age-related diseases.

• Disrupted microbiome: Alterations in the gut microbiome, influencing metabolic function, immune response, and overall health.