My Interventions

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My anti-aging/longevity interventions were selected to directly address all of the currently recognized Hallmarks of Aging. To fully understand those choices, it would be best to first fully understand those Hallmarks.

The Currently Recognized Hallmarks of Aging:

Primary hallmarks (causes of damage)

• Genome instability - damage to DNA that can lead to mutations and cancer.

• Telomere shortening (or telomere attrition) - Each time a cell divides, the telomeres on the ends of each chromosome shorten. Cell division stops once telomeres shorten to a critical length, limiting lifespan.

• Epigenetic alterations - changes in gene expression that can alter cell function. Only a subset of our genes are expressed at any given time. Sections of the DNA chain are spooled on histones, and these histones can be modified to turn specific genes on or off as needed.  With aging, useful genes can get turned off and detrimental ones can get turned on, disrupting the normal functioning of the cell. Various enzymes can trigger these positive or negative changes (expressions). 

• Loss of proteostasis - breakdown of the proteins that cells need to function properly. Proteostasis is the process of maintaining all the proteins necessary for the functioning of the cell in their proper shape, structure and abundance. Protein misfolding, oxidation, abnormal cleavage or undesired post-translational modification can create dysfunctional or even toxic proteins (or protein aggregates) that hinder the normal functioning of the cell. Though these proteins are continually removed and recycled, formation of damaged or aggregated proteins increases with age, leading to a gradual loss of proteostasis. This can be slowed or suppressed by caloric restriction or by administration of rapamycin or plasmapheresis to remove them from the bloodstream.

• Protein Aggregation - Proteins can accumulate and form clumps in cells, leading to impaired cellular function. This is a symptom or consequence of loss of proteostasis, but not the same thing as loss of proteostasis.

Antagonistic hallmarks (responses to damage)

• Deregulated nutrient sensing - disruption of metabolic pathways that regulate nutrient intake. Cells need the ability to recognize normal changes in the concentrations of macronutrient such as glucose, fatty acids, and amino acids, and respond appropriately. Times of both abundance and scarcity should trigger different responses. Improper responses can lead to cancer and accelerated aging. 

• Mitochondrial dysfunction - damage to the organelles that produce energy for cells. During aging, the efficiency of mitochondria tends to decrease. Dysfunctional and ruptured mitochondria contribute to aging through interfering with intracellular signaling and triggering inflammatory reactions. Removal of these damaged mitochondria can delay or reverse the onset of aging and age-related disease.

• Cellular senescence - the accumulation of senescent cells that can't divide or function properly. Telomere shortening, DNA damage, and stress can cause cells to become dormant and cease normal functioning. The proportion of these damaged cells increases exponentially with age due to their secretion of inflammatory markers which signal neighboring cells to also become senescent. Clearance of these damaged cells can delay or reverse the onset of aging and age-related disease.

Integrative hallmarks (drivers of the aging phenotype)

• Stem cell exhaustion - depletion of the cells that can replenish and repair tissues. Stem cells have the ability to self-renew and differentiate into specialized cell types. The proportion of stem cells and the speed of their division gradually lowers over time, causing a loss of regenerative ability and thus, aging. Stem cell rejuvenation can reverse some of the effects of aging.

• Altered intercellular communication - the decline in communication between cells with age, which can lead to a decline in tissue health. Also, acute inflammation serves as a communication method to recruit the body's immune and repair mechanisms to a specific damaged area for as long as the damage and threat are present. But the constant (chronic) presence of inflammation markers throughout the body (such as by senescent cells) wears out the immune system, damages healthy tissue, and can enable senescence in neighboring cells. Through the elimination of senescent cells, altered intercellular communication can be avoided.

Proposed Additional Hallmarks

• Disabled macro-autophagy - used primarily to eradicate damaged cell organelles or unused proteins.

• Chronic inflammation - short term acute inflammation is desirable, but ongoing, continuous inflammation is damaging.

• Dysbiosis - changes in the microbiome, or the community of microorganisms that live in and on the body can contribute to aging. Any disruption to the microbiome of the skin, gut lining, nasal cavity, or vagina, resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution.  

My Main Interventions:

• Exercise - pretty much addresses every hallmark:

  • • Movement to create lymphatic flow to remove cellular waste build-up (along with massage, foam rolling, rebounding, inversion), 

    • Building & maintaining skeletal muscle:

      • • To prevent sarcopenia & frailty

        • Allow for proper glucose & insulin regulation.

    • Build aerobic capacity now, which typically diminishes with age.

• Nutrition & Supplementation - properly addressed, prevents unnecessary epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, chronic inflammation and dysbiosis.  

Properly addressed means:

• • • Consumption of the right foods,

    • Prepared and cooked in the right ways, free from:

      • • Artificial flavorings & colorings,

        • Emulsifiers, 

        • Preservatives, 

        • Pesticides, 

        • Herbicides, 

        • anti-caking agents, 

        • Exogenous hormones, 

        • Endocrine disrupters, 

        • Heavy metals, 

        • Parasites,

        • microplastics,

        • industrial seed oils,

        • transfats

        • and any other unnecessary damaging ingredients

    • along with supplementation to address nutrient, mineral, and enzymatic deficiencies that typically occur with aging.

    • Proteolytic enzymes for enhanced breakdown & absorption of macronutrients.

• Sleep - 8 hours of actual sleep (not just hours in bed) as measured by fitness trackers (Garmin Phoenix 6 Pro, Oura Ring, Whoop Band, Eight Sleep Pod 3 Cover) to remove accumulated waste products from the brain and facilitate bodily repair.

• Limit & Avoid Environmental Exposures - Cleansed air & water via filtering, selecting heath, beauty, and cleaning products that are free of harmful chemicals, heavy metals, endocrine disrupters, dyes and "fragrances", as well as cookware and food & drink storage containers that are free from the same. Other examples of environmental exposures include aerosol sprays, air "fresheners", gasoline fumes, automotive exhaust, trichloroethylene (TCE) in dry cleaning chemicals, phthalates, and bisphenols in cash register receipts.

• Supplementing with:

  • • TAM-818 and TA-65 to produce telomerase for telomere lengthening, in order to halt and reverse telomere shortening.

    • NR/NAD and Sirtuin Activators to address Epigenetic Alterations

• Infrared Sauna - to aid in removal of toxins and interstitial waste build-up, to address misfolded proteins, and to increase heat-shock proteins, Brain-Derived Neurotrophic Factor (BDNF), and growth hormone.

• Cold exposure (cold showers, plunges, and keeping the house temperature cooler all winter) - to reduce inflammation, ramp up mitochondrial efficiency, and improve immunity.

• Time-restricted eating, occasional fasting and rapamycin to address deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, minimize altered intercellular communication, correct disabled macro-autophagy and chronic inflammation.  Because I am now quite lean, in order to maintain hard-earned muscle, my days of doing longer, 5-day fasts are probably over.

• Plasmapheresis (via regular plasma donations) to remove misfolded, oxidized, and damaged proteins, addressing loss of proteostasis, and altered intercellular communication.

• Hyperbaric Oxygen Therapy (HBOT) - for cellular healing/repair, addressing genome instability, epigenetic alterations, and stem cell exhaustion.  Note that HBOT treatments can increase the risk of developing cataracts. To mitigate that risk, I also use N-Acetyl-Carnosine (NAC) Eye Drops.

• Peptides & Oral Peptide Bioregulators - for various organ & tissue repair and regeneration.

• NanoVi - to address oxidative stress, protein misfolding, loss of proteostasis, protein aggregation, and chronic inflammation.

• Stem Cells & Exosomes - for full-body regeneration/healing, and targeted injury repair.

Wishlist:

• Currently existing Gene Therapies, in order of interest - ALL of these are presently out of my reach financially, and still a bit early for my comfort level:

  • • Follistatin - a protein that binds and inhibits myostatin, a growth factor that limits muscle growth. By inhibiting myostatin, follistatin promotes muscle growth and regeneration, enhancing muscle mass and strength, improving physical performance, and potentially combating age-related muscle degeneration (sarcopenia).

    • Klotho - a protein that is associated with regulating multiple biological processes, including phosphate and calcium homeostasis, oxidative stress, and inflammation. It is known to influence insulin signaling and has been linked to enhanced cognitive function, improved kidney function, and cardiovascular health.

    • FOXO3 - a transcription factor involved in cellular processes, offering enhanced stress resistance, improved DNA repair mechanisms, and reduced incidence of age-related diseases.

    • SIRT6 - a member of the sirtuin family of proteins, which play a key role in DNA repair, metabolism, and inflammation, and increased lifespan.

    • TERT (Telomerase Reverse Transcriptase) - an enzyme that offers telomere elongation, delayed cellular aging, and potentially increased lifespan.

    • GDF11 (Growth Differentiation Factor 11) - a protein that has been shown to offer improved muscle regeneration, enhanced cognitive function, and overall tissue rejuvenation.