Rejuvenation and Regeneration

Rejuvenation and regeneration are progressing rapidly towards becoming mainstream medical practices to extend your healthspan and lifespan. Science fiction is becoming science.

“Every generation needs regeneration.” — Charles Spurgeon, 1800s Baptist preacher

“Walk into your local drugstore, you’re going to see about 50 products that claim to be anti-aging, and I can assure you that none of them are.” — Greg Bailey, CEO Juvenescence. Juvenescence raised $220 million from 2018-2020 to fund longevity projects with the lofty goal of extending human lifespans to 150 years. They plan to launch 4 science-backed legitimate anti-aging products by 2025.

Data from a 2020 experiment to restore vision loss in old mice indicates that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—that can be accessed to improve tissue function and promote regeneration in vivo. — Dr. David Sinclair and the Life Biosciences team

“Lifespan is controlled by how well your body can repair and regenerate. Young and old people take the same damage. Young people can repair and regenerate better.” — Irina Conboy

How to Look, Feel and Actually Be Physically Younger!

As noted in our article on What Causes Aging, there are two main categories of factors which influence biological aging, programmed and damage-related. Programmed factors follow a biological timetable, such as those that regulate childhood growth and development and increase our chance of survival until we can produce children.  This regulation is enabled by changes in gene expression which also affect the systems responsible for maintenance, repair and defense responses. Damage-related factors include internal and environmental assaults on our bodies that induce various levels of cumulative impairment and dysfunction, including in our DNA.

To defy aging and stay eternally young is a continuous four-part process:

1. For older adults, you must rejuvenate your body to its desired youthful state. 
2. You must stop the programmed aging process. (See Reversing-Aging.)
3. You must repair damage rapidly through healing and regeneration. 
4. You must not die. (See Brain and Body Protection.)

This article focuses on #1(Rejuvenation) and #3 (Healing / Regeneration).

Rejuvenation Targets

As you see people age, what do you notice most? Their wrinkled skin? Loss of muscle-tone and flexibility? Loss of hair? Dwindling eyesight? Or impaired brain function?

There are multiple areas for whole-body rejuvenation that are being commercially targeted. Some of the most important include:

• Blood and Plasma
• Brain
• Cells (See Cellular Reprogramming)
• Eyes (See 2020 Vision Eye Care)
• Hair (See Keep Hair)
• Muscles (See Strength Training: Power Up! and Flexibility and Pliability)
• Skin (See Feel Comfortable in Your Own Skin) 

This article covers Blood and Plasma rejuvenation along with your Brain as well. The latest scientific research on Blood and Plasma rejuvenation is game-changing, with benefits possible today. It directly impacts the youthfulness of your brain, eyes, hair, muscles and skin.

Blood and Plasma Rejuvenation — Clean Out Accumulated Junk

A major key to rejuvenation is to cleanse your blood plasma. You may have heard of recent experiments of transfusing young blood into old people to rejuvenate them from scientifically-light, companies such as Ambrosia who were shut down by the FDA as a scam in February 2019, then reopened briefly as Ivy Plasma and then briefly operated in semi-stealth as Ambrosia Plasma. Under any name, they are not a good health risk.

Expert scientists led by Drs. Irina and Michael Conboy at the Conboy Laboratory for Engineering Longevity at UC-Berkeley, looked deeper into the early research and made a fascinating discovery. It was not the young blood which brought the benefits. Instead, the benefits were traced to removing the old blood plasma and the buildup of aged protein debris which were biologically interfering with youthful healthy processes in the body. There are similarities with ongoing research to remove senescent cells from the body as well, however blood dilution does more than just limit SASP (Senescence-associated secretory phenotype), which leads to death and detriment of normal cells. Blood dilution removes the main toxic components of myostatin and elevated TGF Beta family proteins. Inhibiting these also shows some rejuvenation effects.

They have demonstrated in animals that aged blood can be filtered of the pro-aging factors which cause inflammation and prevent healthy tissue regeneration and repair, thus leading to rejuvenated, biologically younger mice. 

Plasma is 90% to 95% salt water, making up a little more than half of the body’s blood volume. The primary and most critical plasma protein is albumin. The primary role of albumin is regulation of the system that determines when molecules move into tissues from the bloodstream or out of tissues to be disposed of as waste. So cleaning the blood plasma allows the tissues and organs of your body to dispose of unhealthy waste products as well.

The Conboy team, through their IMYu startup, have partnered with industry-leading expert Dr. Dobri Kirpov to create improved filtration methods for a two-hour FDA-approved routine procedure called plasmapheresis or Therapeutic Plasma Exchange (TPE). This is similar to kidney dialysis except it removes harmful antibodies from the blood. They are raising funds to initiate clinical trials designed to achieve approval for treatment of a number of degenerative, metabolic and inflammatory diseases of aging. 

For our cars and trucks to run well, we change the oil every 5000-10,000 miles.  Science is beginning to show proof that running your body on clean blood is likely to keep it going much better and much longer too. Early 2022 IMYu research on three people demonstrated that old people reset to younger states through TPE regained the younger blood proteins that control brain health and function, homeostasis and regeneration, and immune responses.

How frequently our blood will need to be cleaned to stay young is one of the key research questions. Will TPE become part of your annual physical?

Competitors to IMYu include:

• Elevian is developing 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 by promoting blood vessel formation. 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. However, GDF-11 has a very strong association with human cancer growth and is a risky target. 
• Alkahest is developing clinical candidates to increase or decrease the levels of specific chronokines, the proteins that increase or decrease with age to either promote innate and natural restorative biological processes or inhibit pathological degenerative processes. They have struggled to identify correct targets and achieve success in early trials. However, they are finding some interesting results blocking a blood-brain barrier molecule to maintain brain health.
• NuGenics Research, Dr. Harold Katcher and Dr. Steve Horvath conducted plasma experiments which dramatically reduced the biological age of old rats. They believe their work comes from specific protein replacement from the blood of young rats. This conflicts with the discovery of the Conboy team. Indian startup NuGenics is based in Mumbai and focused on creating an elixir for humans. There does not seem to be a website and no new information has been published since 2020. In 2022, further research from the Conboy laboratory has shown that mixing the blood of young and old mice reduces the lifespan of the young mice and only slightly increases the lifespan of the old mice.

Hopefully at least one of these four companies will emerge with FDA approval for safe human rejuvenation in the next few years.

Brain Rejuvenation — Avoid Age-Related Functional and Memory Loss 

Impaired brain function is perhaps the scariest part of aging. Not being able to think quickly or focus on what’s important or recall words and memories is terrifying. So what is possible today to reverse the effects of aging on your brain? Here is some of the top research:

1. As we age, increasing brain stiffness causes dysfunction of brain stem cells needed for normal brain function and the regeneration of myelin, the fatty sheath which surrounds our nerves. The effects of age in these cells contribute to multiple sclerosis, but their function also declines with age in healthy people. It turns out that by placing these dysfunctional older stem cells back into a soft spongy brain, they are rejuvenated, and  behave like the younger, more vigorous cells. It turns out that a protein called Piezo1 found on the cell surface informs the cell whether the surrounding environment is soft or stiff. Deleting Piezo1 in the stem cells within the elderly rat brains, led to the cells becoming rejuvenated and once again able to assume their normal regenerative function.
2. The hypothalamus plays a crucial role in controlling aging. At the Albert Einstein College of Medicine, Dr. Dongsheng Cai and his team located the specific cells that are responsible for the aging process: neural stem cells also involved in neurogenesis – that is, the creation of new brain neurons. The researchers noted that the number of brain stem cells in the hypothalamus steadily decreases with time, and this impacts the speed at which the aging process unfolds. Their study has shown that this process can be counteracted by adding fresh stem cells to the hypothalamus, but who wants to have that done on a regular basis?
3. Athira Pharmaceutical (NASDAQ: ATHA) is a publicly-traded company focused on restoring neuronal health through small molecule therapies promoting natural brain repair. They have 3 candidates in early clinical trials.
4. Healing the scar tissue from brain injuries is now also possible. Research from Dr. Gong Chen discovered that glial tissue can be reversed back to neuronal tissue through neuroregenerative gene therapy involving four core drugs.
5. A 2020 study discovered that inhibiting intracellular brain stress restored youthful brain function in mice.

Healing and Regenerative Medicine: Growing Cells, Tissue, Organs and Limbs

If you are a person of average size, on a given day, roughly 330 billion cells in your body die and are replaced by new ones. Within about 80 days, enough cells are replaced to match the weight of your body. The Weizmann Institute in Israel has created a baseline for the composition of cell types in the human body and are analyzing how these capabilities are lost with age.

Although all animals can heal wounds, some are capable of reconstructing their entire bodies from small fragments of the original organism. Research on The Genetics of Whole Body Regeneration has led to discoveries helpful in healing humans. 

Leading-edge work to heal and regenerate cells, tissue, organs and limbs is happening. Here are some examples:

• Wake Forest Institute of Regenerative Medicine led by Anthony Atala
  • ~400 researchers have engineered human replacement tissues and organs in four categories – flat structures, tubular tissues, hollow organs and solid organs.
  • In human patients, have provided 15 cell/tissue therapy technologies, such as skin, urethras, cartilage, bladders, muscle, kidneys and vaginal organs.
  • Here’s how they do it using 3D bioprinting.
• Prellis Biologics and over 20 other commercial companies are working on human tissue and organ bioprinting for humans.
• eGenesis and Revivocor are working on xenotransplantation, growing organs in pigs for use in humans.
• Morphoceuticals (using bioelectrics), Lygenesis (using lymph nodes as bioreactors) and Juvena Therapeutics (using novel signaling proteins that can regenerate any tissue type) are creating ways to initiate regeneration in vivo to rejuvenate lives.
• The Levin Lab at Tufts works on using bioelectric signaling to induce targeted regeneration.
• Michael West of AgeX (NASDAQ: AGE) is working on an induced tissue regeneration therapy to reverse aging using a cocktail of small-molecule drugs to change the state of genes. The AgeX technology is intended to repair serious injuries and even regrow missing limbs. Most applications are 5-10 years away from human trials while they focus on technologies which are easier to commercialize. 2021 plans to initiate a Phase 1 trial to regenerate heart function for those with chronic failures did not move forward.
• Turn.Bio — mRNA medicines that induce the body to heal itself by instructing specific cells to fight disease or repair damaged tissue. By reprogramming the epigenome – a network of chemical compounds and proteins that control cell functions by influencing which genes are active – they aim to restore capabilities often lost with age.

Conclusion

In conclusion, there is promising research backed by deep science which will rejuvenate the lives of many people in the relatively near future. Hopefully this article has inspired you to stay healthy until you can take advantage of these new technologies. As your reward for reading and focusing on keeping healthy, check out this Warren Miller video on Snow Kayaking. It is safer to watch than participate, well at least until you can regenerate any damage sustained in doing so.