Reversing Aging

Reversing Aging

Reversing Aging in Humans by 2025-2030, Pets Now?

For hundreds of years, scientists have predicted finding a way to reverse aging within 5-10 years. They still believe that this timeline is accurate. Now, they are finally getting close because we are at an inflection point where we can:

  • See how the body works at the molecular level
  • Modify our genomes and microbiomes
  • Analyze vast amounts of data with powerful computing and machine learning
  • Produce synthetic biology at the nanoscale level
  • Share and collaborate on science globally

Scientists have figured out how to increased the lifespan of roundworms by 500%. They’ve also figured out how to reverse aging and disease in dogs and mice. There are advantages on first commercialized age-reversal technologies on pets because owners can treat their pets without FDA regulation. Rejuvenate Bio is developing a novel cardio-protective gene therapy to stop the progression of heart failure in dogs. Animal Biosciences is working on anti-aging and protective solutions for dogs, cats and horses. Stanford researchers, led by Tony Wyss-Coray, have discovered that blocking an immune-related molecule lodged in blood vessels stops memory loss in mice. The same molecule exhibits similar behavior in humans.

To determine whether aging can be reversed, there needs to be a proven way to determine your biological age (as compared to your chronological age). For example, a fifty year old may have the relative health of an average, younger, or older person. Various companies attempt to determine your biological age, including:

  • Health Nucleus — full body and genetic scan to set health baseline. Does not calculate an “age” per se, but does compare the health of your body parts compared to those of a similar actual age.
  • Life Length — computes an age from a blood test on the health of your telomeres
  • RealAge — science based online assessment

Some scientists believe there are simpler, cheaper and more accurate ways to do this by asking “How old do people think you look?” and checking on “How fast do you walk?”. Their results have been rather accurate. If you don’t want to ask people or don’t trust their answers, you can even upload your photo to this age testing website to have an AI determine how old you look. Cool concept except that the website doesn’t provide results! Hopefully it gets fixed or someone else creates a working version soon.

Once you’ve calculated your biological age, there are nine key biological areas to address What Causes Aging in humans. There are multiple companies competing to bring you solutions for each of them. In alphabetical order, we provide the biological areas and some interesting companies and research.

#1: Altered Communication and Inflammation

Chronic, harmful inflammation can have a number of causes, including a virus or bacteria, an autoimmune disorder, sugary and fatty foods, or the way you handle stress. It can also come as cells age and fail to communicate properly.

  • Focuses on preventing immune system decline and dysfunction
  • Multi-College Research Collaboration (Brown, New York University, the University of Rochester, Université de Montréal, the University of Virginia School of Medicine, and Leiden University Medical Centre in the Netherlands)
    • Found way to halt retrotransposon activity in old cells. Retrotransposons—DNA sequences able to replicate and move to other places—make up a substantial fraction of the human genome.
    • Significantly reduces inflammation caused by senescent cells (see below)
    • Treating 26-month-old mice (roughly equivalent to 75-year-old humans) with generic drug lamivudine for as little as two weeks, reduced evidence of both interferon response and inflammation.
    • Treating 20-month-old mice with lamivudine for six months reduced signs of fat and muscle loss as well as kidney scarring.

#2: Cellular Senescence (Normal cells lose function, cease to divide and resist cell death)

Although our bodies naturally remove some old cells, as we age, many old cells accumulate and cause dysfunction. Eating colorful fruits and vegetables helps because Fisetin slows aging by removing senescent cells, however that is not enough. These companies are making rapid advances:

  • Unity Biotechnology (NASDAQ: UBX)
    • Focused with a pipeline of solutions to deliver localized therapy
      • For osteoarthritis in knees
      • For ophthalmology including age-related macular degeneration and glaucoma
      • For pulmonary disease
    • Beyond cellular senescence, they are uncovering mechanisms that contribute to age-related diseases including mitochondrial dysfunction and loss of circulating youth factors
  • Oisín Biotechnologies (Private Seattle company, founded in 2016 as spinout of SENS)
    • Technology can kill any class of cell with a distinct internal marker in the form of high levels of expression of a specific protein. Senescent cells express high p16.
    • Plan to wipe out all senescent cells in one blast
    • Challenges include:
      • “Not every cell that expresses high p16 is senescent; and not every senescent cell has high p16,” notes James Kirkland, a researcher who studies aging at the Mayo Clinic.
      • No new news on website since July 2018…
  • Ichor Therapeutics private portfolio companies
    • LysoClear — Removing toxic vitamin A aggregates which bind with native lysosomal enzymes, inhibiting their function and causing macular degeneration
    • Antoxerene — Developing collection of small molecules to target senescent cells within a joint venture with Juvenescence called FoxBio
  • Senolytic Therapeutics (Boston and Barcelona-based private portfolio company of Life Biosciences, founded in 2017)
    • Developing senolytic compounds to target and eliminate senescent cells in fibrotic diseases and certain cancers. Preclinical stage for Idiopathic pulmonary fibrosis (IPF), a form of lung cancer
    • Developing immune system-mediated clearance of damaged cells to improve post-oncological treatment
  • Cleara Biotech (private Netherlands company founded in 2018)
  • University of Exeter
    • Found that stopping the activity of the pathways ERK and AKT, that communicate signals from outside the cell to the genes, reduced the number of senescent cells in cultures grown in the laboratory
    • Knocking out the activity of two genes controlled by these pathways – FOX01 and ETV6 can bring about at least a partial reversal of key elements of the aging process in human cells
  • Mayo Clinic

#3: DNA Damage / Chromosomal Instability

Free radicals, reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physicochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body’s ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Scientists are testing a potential solution called Nanoceria on a space shuttle for reducing oxidative stress damage

As cells age, mitochondria become more inefficient and dysfunctional. When they don’t function properly, they can produce an altered form of oxygen that can cause damage to DNA and proteins. The leading potential solution for DNA-protection and repair is NAD+. Also, Vera Gorbunova’s lab has found that the gene sirtuin 6 (SIRT6) is responsible for more efficient DNA repair in species with longer lifespans.

#4: Gene Expression Errors / Epigenetic Alteration (can cause a broad range of disease)

The recent discovery is that wrinkly cell membranes press on genes and accidently activate parts of them which are supposed to be dormant in certain cell types. Removing or repairing these wrinkly cell membranes avoids gene dysfunction.

#5: Imbalanced Metabolism

Metabolism is the process your body uses to get or make energy from the food you eat. Your body can use this fuel right away, or it can store the energy in your body tissues, such as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body disrupt this process, leading to health issues such as obesity and diabetes.

See Keep Health’s Dietary Supplements section for metabolic medicines focused on preventing imbalanced metabolism.

Also, Age Therapeutics is working on brown adipose tissue (BAT) implants that fix the problems of obesity, diabetes and metabolic syndrome. BAT is one of two types of fat that mammals have. Its main function is to turn food into body heat. It is sometimes called “good” fat. Human newborns have high levels of brown fat. It is also present and metabolically active in adult humans, but its prevalence decreases as humans age. Having less good fat to provide body heat may be why older people move to warmer climates for winter.

#6: Protein’s Become Less Functional / Proteostasis

#7: Reduced Cellular Energy Production / Mitochondrial Dysfunction and Vascular Aging

#8: Stem Cell Exhaustion (inability of stem cells to continue to replenish tissues)

#9: Telomere Shortening (associated with aging, mortality and aging-related diseases)

Telomeres are the protective ends of each of your strands of DNA. They gradually decline in length as your cells divide, eventually shortening to the point of DNA dysfunction.

To understand how specific lifestyle and psychological habits protect telomeres, slowing disease and improving life, read the New York Times bestseller, The Telomere Effect, coauthored by the Nobel Prize winner who discovered telomerase and telomeres’ role in the aging process.

In our research, we also found this unique proposal on how to stop cellular aging from high school students! Not sure how accurate they are, but it was well-written. Perhaps they have a future Nobel Prize winner among them.

Bonus: #10 Regeneration – How to Look and Feel Younger!

The nine biological factors above are causing aging. Regeneration doesn’t fit cleanly into any of them, but is getting significant funding for age-reversal. Here are some of them.

Michael West of AgeX (NASDAQ: AGE) is working on a therapy to reverse aging using a cocktail of small-molecule drugs. The AgeX technology is intended to repair serious injuries and even regrow missing limbs. It is 5-10 years away from human trials while they focus on technologies which are easier to commercialize.

Celularity is a commercial-stage cell therapeutics company delivering transformative allogeneic cellular therapies, engineered from postpartum human placenta, in cancer immunotherapy and functional regeneration.

Elevian is developing a number of therapeutics that regulate Growth Differentiation Factor 11 (GDF11) and other circulating factors to restore the body’s natural regenerative capacity. GDF11 is a key factor in why young blood can restore older organisms to health. GDF11 levels decline with age. GDF11 supplementation reduces age-related cardiac hypertrophy, accelerates skeletal muscle repair, improves exercise capacity, improves brain function and cerebral blood flow, and improves metabolism. Of note, the FDA does not recommend parabiosis, where young blood transfusions are done in hopes of reducing aging. It is unproven and there are serious risks.

Also, here are some interesting articles on leading-edge research:

This concludes our article on Reversing Aging. We hope you will benefit once it is safe and proven.

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