Reversing Aging

Reversing Aging in Humans by 2026-2030, 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 also believe they have figured out how to reverse some aspects of 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 and Phibro Animal Health are developing a novel cardio-protective gene therapy to stop the progression of mitral valve heart failure in dogs. Another company, Animal Biosciences is developing cellular level anti-aging and protective solutions for dogs, cats and horses. Their daily supplement is called LeapYears.

To determine whether aging can be reversed, you need to start by determining 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. There are a variety of companies providing biological age testing. All have limitations.

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 study results have been rather accurate.

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. 

Researchers are attempting to prevent immune system decline and dysfunction. See Immunity Against Aging for updates on their progress.

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

Although our bodies naturally remove old cells as we age, some old cells survive and cause dysfunction. Eating colorful fruits and vegetables helps because Fisetin (see also this ongoing clinical trial) slows aging by aiding in removing senescent cells, however that is not enough. Also, it is important for cells to become senescent as a barrier to cancer. People with low senescence have a high risk of neoplasms.

These six companies are seeking solutions to clear cells once they become senescent:

• Cleara Biotech (private Netherlands company founded in 2018)
  • Uses an engineered peptide molecule FOX04-DRI to destroy a particular subtype of senescent cell.
  • As of 2019, still too dangerous for human trials. Still in preclinical research to create a safe version.
  • Lightly funded. 2.5MM seed round in 2022. Hired new CMO in 2023.
• Mayo Clinic
  • Dr. James Kirkland and the Mayo Clinic worked on senolytic drug clinical trials to reduce frailty in people with chronic conditions. Results were mixed.
  • They tested the anticancer drug dasatinib along with plant-based nutrients (quercetin, theaflavins, fisetin and related compounds).
  • They formed the Translational Geroscience Network to coordinate anti-aging work across 8 research institutions.
• 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. Initial therapeutic focused on chronic kidney disease.
  • As of 2023, targeting removing visceral fat and adding muscle via follistatin therapy.
  • 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.
    • Lightly funded. $5MM seed round in 2021. 
• Rubedo Life Sciences
  • Targeting age related diseases impacting elderly using small molecule senolytic agents using galactose moieties called RB1000. Similar, but more complex and advanced approach to Serrano and failed (senesced?) company Senolytx.
  • Take advantage of different metabolic functions and warheads to go systematically across tissues. Different compounds for different contexts. There is not one cure for all. 
  • Preclinical pipeline. Targeting aging-related skin conditions such as dermatitis and psoriasis. 12 million in funding.
• Senisca
  • Based on University of Exeter research from Dr. Lorna Harries, 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
  • Preclinical. Raised $2MM seed round in 2022 and $4MM in March, 2024.
•  Unity Biotechnology (NASDAQ: UBX)
  • Small molecule targeting Bcl-xL, a protein that senescent cells rely on for survival.
  • Focused on a pipeline of solutions to deliver localized ophthalmology therapies. Current primary target is diabetic macular edema. Other trials have not produced sufficient results for commercialization.

#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.

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)

Environmental factors such as diet, temperature, oxygen levels, humidity, light cycles, and the presence of mutagens can impact how your genes are expressed. Errors during gene expression come from transcription and translation mistakes. For a coding gene with around 300 to 400 codons, approximately 10% to 20% of the proteins made contain at least one error (!), such as missense incorporation, frameshifting, or stop codon readthrough. These alterations are called mutations, and can accumulate over a lifetime. Multiple concurrent mutations in genes that control cell division can cause cancers. Scientists are looking for ways to reduce or prevent gene expression errors.

The recent discovery is that wrinkly cell membranes press on genes and accidentally activate parts 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 discovered brown adipose tissue (BAT) implants can 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. Sadly, Age Therapeutics failed to raise funds to commercialize this discovery.

#6: Protein’s Become Less Functional / Proteostasis

Proteostasis means that each function dependent on proteins is running as it should. Unfortunately, proteostasis breaks down as we biologically age. For more, see our article on how to Keep Your Proteins in Shape.

#7: Reduced Cellular Energy Production / Mitochondrial Dysfunction

Potential solutions include:

• Dietary supplement Nicotinamide Riboside produces NAD+ , the communication molecule between the cell nucleus and the mitochondria which are the energy producing factories in the cell. If NAD+ levels are low, communication may be impaired and mitochondrial dysfunction may result. When this occurs, everything begins to breakdown.
• Rejuvenation of mitochondria with a tiny quantity of hydrogen sulfide
  • Study
  • Summary article
• Mitrix Bio — growing mitochondria for transplantation to bolster energy production and regenerate aged or dysfunctional tissues. That said, 10% of your body weight is mitochondria and your body produces an immune response when it detects free-floating mitochondria in your bloodstream.

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

There are five types of stem cells.

• Hematopoietic Stem Cells (Blood Stem Cells)
• Mesenchymal Stem Cells.
• Neural Stem Cells.
• Epithelial Stem Cells.
• Skin Stem Cells.

As we age, these stem cells eventually lose their ability to divide and we are unable to replace the stem cells that have migrated, differentiated, or died. Stem cell exhaustion occurs from this decline in stem cell numbers and renewal capacity. Without stable populations of proliferating stem cells, our bodies lose their ability to recover from damage and begin to fail.

Scientists are using animal models to discover ways to regenerate and replace stem cells, including in Flatworms and Mice. As for humans:

• In 2019, in an attempt to rejuvenate his body, Star Trek star William Shatner opted to undergo a relatively new medical treatment. At the time, the 88-year-old actor tweeted that he’s received restorative stem cell treatment from the company ProGenaCell. “Today I received restorative stem cells from my good friend Greg DiRienzo at ProGenaCell,” Shatner tweeted. “The stem cells were manufactured by Invitrx here in So Cal. My friend Dr Mathi Senapathi gave the cells to me intravenously. Is it possible to turn back the clock? I will let you know.” As of 2024, he’s now 93 years old. 
• Longevity supplement company Novos recommends glycine and alpha-ketoglutarate to slow your biological aging of stem cells.
• To keep your blood stem cells healthy until easy bone marrow rejuvenation techniques become available, the Cleveland Clinic recommends eating a diet rich in protein (lean meats, fish, beans, nuts, milk, eggs) combined with making sure to maintain healthy levels of iron and vitamins B9 and B12. See our article, Bloody Good Health to learn more about bone marrow aging.

#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.

Conclusion of Reversing Aging

This concludes our article on Reversing Aging. We hope your life doesn’t conclude before solutions are safe, proven and readily available!

As your reward for reading and taking care of your health, why stop with reversing aging. How about reversing extinction? George Church’s team at Colossal is trying to re-engineer woolly mammoths and create the world’s first Pleistocene Park! Their journey is quite fascinating. Check out either Woolly by Ben Mezrich (2018), How to Clone a Mammoth by Beth Shapiro Chief Science Officer of Colossal  (2016) or De-Extinction by Rebecca Hirsch (2017).