Diluting Plasma Slows Aging, New Mouse Study Suggests

University of California, Berkeley researchers have recently published a mouse model study that shows age-reversing effects can be achieved by diluting the blood plasma of old mice.

In 2005, University of California, Berkeley, researchers made a surprising discovery by stitching together a young and and old mouse like conjoined twins. Sharing blood and organs between the mice, scientists rejuvenated tissues and reverse the signs of aging in the old mice.

This conjoined twin mouse model study led to the idea that young blood contains special proteins, which deliver a ‘fountain of youth’ effect. And biohackers got the idea that getting transfusions from young donors aka “blood boys” could slow aging.

Problem is mouse studies are not a strong signal and exploratory. A follow on mouse model study conducted by the same research team, now shows simply diluting the blood plasma of old mice achieves age reversing effects.

Here’s how parabiosis became a thing:

Early 2000s – Senior researcher and professor of bioengineering Irina Conboy and Michael Conboy have a hunch that our body’s ability to regenerate damaged tissue remains with us into old age in the form of stem cells. But that somehow these cells get turned off through changes in our biochemistry as we age.

2005 – Conboy lab publishes study showing that making conjoined twins from the old mouse and a young mouse reversed many signs of aging in the older mouse. Many researchers seized on the idea that specific proteins in young blood could be the key to unlocking the body’s latent regeneration abilities.

2016 – a second follow-up study finds young blood does not reverse aging in old mice. Tissue health and repair dramatically decline in young mice when half of their blood is replaced with blood from old mice.

The study suggests to Irina Conboy that young blood by itself will not work as effective medicine. Rather the idea that emerges is that inhibitors in old blood could be a target to reverse aging.

In this 2016 study, Conboy and colleagues developed an experimental technique to exchange blood between mice without joining them so that scientists can control blood circulation and conduct precise measurements on how old mice respond to young blood, and vice versa.

In the new system, mice are connected and disconnected at will, removing the influence of shared organs or of any adaptation to being joined. One of the more surprising discoveries of this study was the very quick (within 24 hours) onset of the effects of blood on the health and repair of multiple tissues, including muscle, liver and brain.

June, 2020 – A new study finds that diluting blood in old mice by replacing half of the plasma with a saline and albumin mixture was able to reverse aging in the brain, liver, and muscle.

In a press release statement Irina Conboy, a professor of bioengineering at UC Berkeley who is the first author of the 2005 mouse-conjoined twins paper and senior author of the new study explains the results:

“There are two main interpretations of our original experiments: The first is that, in the mouse joining experiments, rejuvenation was due to young blood and young proteins or factors that become diminished with aging. But an equally possible alternative is that, with age, you have an elevation of certain proteins in the blood that become detrimental, and these were removed or neutralized by the young partners.”

In the years since the exploratory 2005 study, scientists have spent millions to investigate the potential medical properties of youthful blood with enterprises emerging to infuse old people with young blood.

“What we showed in 2005 was evidence that aging is reversible and is not set in stone,” Irena Conboy said in a UC Berkeley press release. “Under no circumstances were we saying that infusions of young blood into elderly is medicine.”

What the Hack? 5 Popular Biohacks vs. Science

Biohacking is taking off. Fueled by tweets from the likes of entrepreneur Jack Dorsey, there’s something appealing about the self-experimenting scientist nerd.

“Hackathons” have been a pastime for tech geeks for years. Software engineers fix bugs and come up with new ideas in hackathons that stretch through the night.

Today this fix-it nerd approach to hacking software code, is applied to our own biology by broscience and biohackers (who sometimes hold degrees in biochemistry).

And Covid has led to a renewed interest in ways to boost the immune system.

The voice of science may be getting drowned out by the sheer volume of health influencers in social media. And it’s getting harder to distinguish signal from the noise.

Scientists and biohackers are driven by a shared sense of curiosity and a desire to help people feel better. But both camps do not disseminate information in the same way.

Scientists run clinical trials. The average cost of phase 1, 2, and 3 clinical trials across therapeutic areas is 4, 13, and 20 million respectively. Pivotal studies cost a median of $41,117 per patient.

Science also follows the credo that “correlation does not imply causation” in regards to observational or epidemiological studies. The randomized, double-blind placebo control is the gold standard for designing an experiment or testing a new drug. If a clinical trial involves only a small number of patients the data is considered as a pilot study (or weak signal), and other labs will try to repeat and validate the results. And those results will be peer-reviewed before publication in a science journal.

Biohackers on the other hand are self-experimenters, and will share “N of 1” data from their own personal self-experiments. An N of 1 trial is a clinical trial in which a single patient is the entire trial. Results are blast out on social media and sometimes linked to product promotions.

In the biohacker realm, a boost to the immune system is sometimes discussed as a productivity or work hack.

Hackers in the early days of Silicon Valley learned about something by building, and trying to make things and seeing what happens. The biohacker hands on approach worked well for building computer keyboards and hardware. Scientists on the other hand work on the body that as a complex system has multiple sites of action. When a drug is working at one site, it is working and doing things all over the body. Side effects are caused by a drug working on multiple sites of action.

But the general public that hears an idea that’s been popularized by biohackers, probably doesn’t know about potential side effects. Scientific research is published in journals that the average Joe Q. Public doesn’t read. How does science get out there on the airwaves?

Increasingly, media-savvy scientists are also creating apps, giving TED talks, and doing Facebook Lives. But still the demands of research, the pressure to publish, and the expense and difficulty of designing a good clinical trials, means less time to post YouTube videos.

With Covid and a higher volume of non-peer reviewed preprints and Twitter spreading science faster than ever on social media, this issue may be coming to a head.

Here’s five simple ideas about health scientists worry we may be getting wrong:

ONE – Free Radical Damage is Bad

The idea “free radicals bad, antioxidants good” is everywhere. But in the past ten years, several scientists are calling into question the Free Radical Theory of Aging which was first proposed in the 1950s.

What’s less well recognized is that the body has its own antioxidant system, which is more powerful than any pill.

Somewhat counterintuitively, free radical damage from exercise is beneficial because it causes helpful adaptations like an increase in muscle strength and mitochondria growth.

According to sports science research, Reactive Oxygen Species (ROS) and oxidative damage, are a normal part of biology and something that cells in the body are equipped to neutralize. Besides causing wrinkles, Reactive Oxygen Species (ROS) are key signaling molecules that trigger muscles to grow. 

Exercise triggers an antioxidant system that exists in the body’s cells, blood, and organs. And when it comes to antioxidant supplements – timing matters.

Emerging research suggests that taking antioxidants (in particular Vitamin E) right before or after training may blunt some of the benefits of working out, like mitochondria biogenesis.

Mitochondria are the powerhouses in your muscles that mop up glucose and are important to insulin sensitivity and preventing diabetes. There is some conflicting evidence and more trials are underway. But for now, experts in exercise physiology advise athletes to proceed with caution.

For elite athletes, taking a mega-dose of Vitamin E and C before or right after training may in fact be doing more harm than good.

TWO – High Protein Intake Can Accelerate a Key Aging Pathway

Biohackers talk about the benefits that come from getting into ketosis from mental clarity to getting six-pack abs.

But high protein diets may also increase levels of an important aging biomarker called insulin like growth factor or IGF-1 levels in humans.

The master axis the mammalian target of rapamycin mTOR pathway is a primary aging pathway that senses amino acid concentrations and regulates cell growth, and integrates other pathways including insulin. mTOR plays a key role in metabolism, and important roles in the function of tissues including liver, muscle, and the brain. It is dysregulated in many human diseases such as diabetes, obesity and certain cancers.

IGF-1 is a blood test used in the clinical setting as a biomarker relevant to preventing age-related diseases like diabetes, cancer, and Alzheimers.

Going on a high animal protein, keto diet may result in six pack abs. But given the science, keto dieters may also want to get bloodwork done.

THREE – Dark Chocolate Doesn’t Contain Exogenous Antioxidants

An important protective pathway called Nfr2, enhances the body’s antioxidant defense. A wide variety of bioactive nutrients in a whole food diet are capable of activating Nrf2 signaling pathways. One of the biggest benefits of Nrf2 is how it protects against inflammation.

Exercise, sleep, and a high nourishment diet appear to keep this antioxidant system working optimally.

Bioactive nutrients in a whole food diet can activate Nrf2 signaling pathways. Nrf2 pathways protect your cells from stressors. The pathway appears to play an important role as a master regulator of more than 200 protective genes that shield your cells against toxins and harmful agents.

Ultimately food does not deliver an exogenous dose of antioxidants.

Consuming a high quality diet activates a variety of signaling pathways in the body’s antioxidant system, and this in turn helps to switch on protective genes.

So consuming dark chocolate is a healthy choice, but not because the chocolate itself contains antioxidants. The bioactive nutrients or polyphenols in the chocolate activate the body’s Nrf2 signaling pathway to help protect cells from stressors.

FOUR – Some Circadian Clocks Are Run by Eating Window

Biochemical clocks exist in tissues throughout the body. And a cutting edge field of science called chronobiology, is now discovering that how the circadian clocks in our organs, tissues, and cells are tuned matters.

Today we know that there is a decline in circadian rhythms with age, concomitant with declines in the overall metabolic tissues homeostasis and changes in the feeding behavior of aged organisms. This disruption of the relationship between the clock and the nutrient sensing networks might underlie age-related diseases.

According to Dr. Satchin Panda, an expert in circadian clock research, when the timing systems in the human body are desynchronized, essential organs are compromised, reducing the potency of the immune system.

A recent breakthrough in Panda’s lab suggests that a primary time cue may not only be light, but glucose – and this happens in the circadian clocks in the liver and pancreas.

When we start the liver clock (by taking our first sip or bite of the day) appears to have effects on glucose, lipid and oxidative pathways and immune system rejuvenation and repair.

Eating in an eight hour (or even 10-12 hour window) may tune the circadian liver clock to significantly improve immune system health.

Panda’s lab is currently running a 9,000 patient clinical trial using an app called mycircadian.org to test this drug-free, cost-effective, lifestyle choice as a way to prevent insulin resistance and other disease risk factors.

According to several early clinical studies in humans, your liver has a circadian clock that is switched on and regulate thousands of genes.

“There is a [circadian] clock in the liver. Forget about light or dark,” says Panda. “What we have to be more careful about is when we eat and when we fast.”

In other words, researchers are learning that beyond jet lag, there’s also metabolic jet lag. More and larger human clinical trials are needed.

But for now, “metabolic jet lag” appears to play a more important role in immune system health than was previously thought.

FIVE – Your Stem Cells Have a Built-in “Homing Beacon”

The picture of regenerative medicine portrayed on blogosphere is that rejuvenating stem cells requires painful needle, a lot of money, and or a potential trip to a clinic outside the US.

Science is now focusing on a different angle.

Mesenchymal stem cells (MSCs) are multipotent stem cells found in bone marrow that are important for making and repairing skeletal tissues, such as cartilage, bone and the fat found in bone marrow. These are not to be confused with haematopoietic (blood) stem cells that are also found in bone marrow and make our blood.

Everyone has these stem cells inside our bone marrow, which are in stand by mode or quiescence.

What is less well understood or talked about in the broscience is that injecting a needle into damaged tissue isn’t the only way to direct stem cells to the site of damage.

Stem cells appear to operate like heat-seeking missiles, equipped with a “homing beacon”.

It was once thought that the decline in mesenchymal stem cells as we age was a given.

But now science is learning that the microenvironment that your stem cells are in can have a dramatic impact on their ability to grow, proliferate and repair damaged tissue. Stem cells can be impacted by diet, exercise and taking mediations.

In the world of biohacking getting a stem cell injection is portrayed as a way to slow aging. But science is now learning that nutrition may be able to trigger stem cells out of quiescence to rejuvenate the boy.

Scientists at USC in a mouse model study observed an 800% increase in the proliferation of

Clinical trials in humans using muscle tissue biopsies are hoping to validate the study and find out how stem cells proliferation or differentiation works as triggered by changes in nutrition.

At the very least, science is learning that nutrition (or pulsing a five-day low calorie period with refeeding) may produce more powerful effects on stem cells than previously understood.

While more studies are needed, science is learning that nutrition and manipulating nutrient-sending aging pathways (no needle required) appears to have positive effects on stem cell health.

Covid as a health crisis is also providing scientists with an inflection point. People under quarantine have time to stop and evaluate their health. But with today’s rise of biohacker culture, getting valid science from the lab bench to the pop culture milieu for wellness – might take a revolution.

Taking Vitamin E Before Exercise, Could Blunt Benefits

The idea “free radicals bad, antioxidants good” is everywhere.

But according to the latest research in sports science, it’s not that simple.

According to Dr. Rhonda Patrick, a PhD in biomedical science: “Taking antioxidants pales in comparison to the power of the antioxidant system your body has on board to handle the effects of Reactive Oxygen Species (ROS).”

Your body has its own anti-oxidant pathway, floating around in your cells, blood, and in enzymes. This network of enzymes includes glutathione, CoQ10, and superoxide dismutase, and is triggered by exercise.

In 1956 the Free Radical Theory of Aging was proposed by Denham Harman and it proposed that aging is a progress of damaged cells and oxidative damage was bad.

Exercise is a major source of oxidative stress. But enzymes like superoxide dismutase and glutathione peroxidase scan the body for reactive oxygen species (ROS) and extinguish the pro-inflammatory sparks caused by exercise.

So if you exercise on a consistent basis, you are also giving yourself a dose of antioxidants. The more you train, the more your body adapts by ramping up its own internal antioxidant production. That’s according to Dr. Marc Bubbs, an expert in sports science and author of Peak: the New Science of Athletic Performance.

If you exercise on a consistent basis, you are also giving yourself a dose of antioxidants.

Dr. Marc bubbs

Studies demonstrate that antioxidant supplementation may interfere with exercise‐induced cell signaling in skeletal muscle fibers (Ristow & Zarse, 2010; Hawley et al . 2011). In turn, changes in cell signaling may potentially blunt or block adaptations to training (Peternelj & Coombes, 2011; Gliemann et al . 2013; Morales‐Alamo & Calbet, 2014).

“Reactive oxygen species (ROS) happens in all the cells of the body, and the body is equipped to handle it,” explains Scott K. Powers, Ph.D., a physiologist at the University of Florida who specializes in investigating the effects of muscular exercise.

Free radical damage, created by a workout will damage muscles. But after the damage, the body’s antioxidant system moves in and produces mitochondria in your muscles via mitochondria biogenesis.

Here’s a brief timeline of the free radical theory of aging to explain:

1956 – Free Radical Theory of Aging proposed by Denham Harman, proposing the early hypothesis that aging is a progress of oxidative damage.

1960s – Mitochondrial biogenesis, the process by which cells increase mitochondrial mass is discovered. It was first described by John Holloszy in the 1960s, when it was discovered that physical endurance training induced higher mitochondrial content levels, leading to greater glucose uptake by muscles.

1969 – Antioxidant enzymes are first discovered and science learns cells are designed to deal with radicals. Free radical damage in cells is a part of normal biology.

1978 – First evidence that exercise-inducted oxidative stress if supplemented with vitamin E, blunts mitochondrial biogenesis in muscle tissue.

1990 – Reactive Oxygen Species (ROS) is discovered.

1990s – Sports science discovers that radicals aren’t just damaging but important signaling molecules, in the context of exercise.

2014 – A randomized control study finds vitamin C and E supplements blunted increase in mitochondrial production and interfered with positive adaptations to exercise in humans. This controversial study says high dosages of Vitamins C and E should be used with caution by elite athletes.

2019 – Professor Gomez-Cabrera, an expert in physiology is invited to speak on a panel on exercise and oxidative stress and clinical trails involving athletes. Her presentation: “Antioxidants in Exercise. Worse Than Useless?”.

According to Gomez-Cabrera, both aerobic and anaerobic training causes an enhancement in the antioxidant enzyme activity in various tissues. This is an adaptation process that happens because the free radicals, produced during muscle contraction, act as signaling molecules. This stimulates the gene expression and, increases production of antioxidant enzymes and modulates other oxidative stress protection pathways, such as enhancing the activity of DNA repair enzymes in skeletal muscles.

Exercise strengthens the body’s antioxidant network system which, consequently, minimizes the oxidative stress process.

Antioxidant protection occurs not only in the muscles but vital organs like the liver and brain, also make beneficial adjustment.

The bottom line is that while YouTube videos everywhere talk up megadose antioxidants, scientists in the field aren’t so sure. Timing matters, and taking supplements close to a workout may do more harm than good.