Current TOP Research and Development Interests and Initiatives

Therapies Planned As Part Of My Own Self Directed Age Management Research, and Other Associates in Our Circle of Scientists, Physicians and Informed Lay People:

www.AgingIntervention.org/1_UpcomingPersonalTherapies.pdf

Contact me for a status report and to let me know about your age management program.

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Levels:

1. Conventional Methods Available Now

Get into and stay in great health, while we make scientific advances.
Nutrition, exercise, stress reduction, sleep well, meditation, cultivating happiness, adequate amounts of water, reduce risks, and others.

2. Potentially Advanced Methods Available Now To Be Used Under Expert Guidance
Prescription medications repurposed to slow or intervene in the underlying causes of age related decline — metformin, and statins for example.

3. Therapies for Regeneration and to Reduce Age Related Decline

4. Intervene in the Underlying Causes, and Repair and Prevent Age Related Decline

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Causes of Aging, Hallmarks of Aging:

Some of the causes of aging recognized by aging intervention scientists for which we will find solutions:
• Oxidation
• Glycation
• Cross-linking, and other chemical modifications acting to impair the molecular functioning of multiple vital components in the body.
o Those affected include DNA, membranes, the extracellular matrix (ECM), enzymes, and structural proteins
• Debris and disorganization both intracellular (inside the cell) and extracellular (outside the cell)
• Alteration in chemical equilibrium of cells (change in redox potential poise) — results in a decreased ability to manage highly reactive and damaging molecules. This causes alterations in gene expression, enzyme activity, and signaling pathways Cell atrophy and loss
• Cell atrophy and loss
• Nuclear mutations in nucleus, including DNA
• Inflammation
• Decrease in repair and recycling effectiveness
• Mutant mitochondria (mitochondria are the energy factories within the cells that also control cellular processes)
• Harmful cells that are resistant to death — visceral fat cells, supernumerary cells (toxic cells that accumulate in the cartilage in our joints and elsewhere) and dysfunctional immune cells

Hallmarks of Aging — distinguishing features or characteristics
www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174
Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging.

These hallmarks are:
• Genomic instability
• Telomere attrition
• Epigenetic alterations
• Loss of proteostasis
• Deregulated nutrient-sensing
• Mitochondrial dysfunction
• Cellular senescence
• Stem cell exhaustion
• Altered intercellular communication.
A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contribution to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging with minimal side-effects.

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Some Recent research:

Small oxytocin study
Oxytocin has multiple benefits in animals: muscle maintenance, attenuates atherosclerosis and inflammation, wound healing, inhibition of weight gain (regular chow and fast food chow), prevents bone loss, testosterone levels and testicular size, robust hair growth, thicker skin, rejuvenated thyroid

Our study cultured lactobacillus reuteri 6475 (gut microflora) in yogurt for one month.  Lactobacillus reuteri 6475 was expected to upregulate the body’s oxytocin production.  Also one subject spiked it with additional BioGaia Gastrus.

Result: Both subjects experienced a lot of long, vivid dreams for about 1/3 to 1/2 the night.  No increased empathy.

Though parts of it were somewhat inconclusive, what worked in animals didn’t work in humans.  One subject: increased libido, and negative mood with some depression upon discontinuing.

De-methylation and Horvath epigenetic clock as true biomarker of aging and evidence of intervention results.

Aging biomarkers and other measures of results of studies — great interest is inflammation

Pilot / beta / small study trial format protocol in humans
Practical, small, informal, fast track, cautious and low risk, MD monitored and controlled method with aging biomarkers and biological/health measures, conducted by a small group of associates.

Planning:
Plasma transfer / exchange and/or unbilical cord blood plasma - Our team’s research indicates these are our best near-term opportunities.  They probably improve the aged microenvironment thereby promoting tissue-specific stem cell activation in most systems.
“Circulating Systemic Environmental Factors” (CSEFs) are believed to be the reasons.

  • Circulating cytokines and chemokines (such as CCL11)
  • Growth factors (such as the transforming growth factor-β superfamily member GDF11)
  • MicroRNAs that can epigenetically regulate gene expression
  • Multiple effects

Other Areas Of Interest:

Personalized medicine – find our own personal weak link and fix it
Engineered organs
Mitochondria repair and regeneration
Lipofuscin (cellular debris) removal — remove amyloid beta and systemic amyloids
Crosslinks breaker
Stem cell research and gene-editing experiments, with the express intention of delaying aging and rejuvenating vital organs.
Lipsosomes/liposome delivered therapies
Liposomal forms of supplements to lower inflammatory response (4 herbs)
GDF-11
NRG-1
Evrolimus
NAD or precursor like NMN or NR –Vince and Jim
C60
Lamin A
Clear garbage, senescent cells / autophagy
Constant improvement/multiple functionalities – and Find our own personal weak link
Rapamycin variations (inhibitor of growth signaling)
Metformin (Caloric restriction mimetic?)
maybe combined with a specific strain of E. Coli?
Aspirin/ibuprofen (anti inflammatory)
Caloric restriction
Caloric restriction mimetics
Thioflavin T (anti-amyloidogenesis)
N-tert-butyl-α-phenylnitrone (antioxidant)
Resveratrol (Sirtuin activator)
Benfothiamine (anti-glycation)
Motivation (compliance) for better lifestyle — nutrition, exercise, meditation and stress reduction, others

Improvements over current mouse testing
Engineered (lab grown) tissue systems — heart, liver, lung, kidney, brain and others
connected by blood supply
for evaluation and screening of aging interventions and other therapies
as an improvement or supplement to animal and computer simulation testing.

Each heart, liver or other module is usually called an organ-on-a-chip, or tissue chip.

Defined: A multi-channel 3-D microfluidic cell culture chip that simulates the activities, mechanics and physiological response of entire organs and organ systems.  The term seems misleading as it implies something like a computer chip.

Public awareness and fundraising (current and upcoming)

- Speaking engagements

- Fundraising

- Press/news articles and talk show appearances

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