Joys of Fasting

After taking my beloved wife to the airport yesterday morning, I realized that I had a perfect opportunity to try out an extended “Fast” without endangering my relationship if my mood got cranky and without needing to refuse the good food she prepares.

So yesterday I ate nothing.  It’s now about 36 hours since I last ate, and I’m feeling great:  Clear, light, optimistic, energetic.  A very welcome change from the heavy, sluggish, abused way I felt after allowing myself to binge on cake, ice cream and/or chocolate several times in the last couple of weeks.

This morning the gym scale said I weigh 182.  (Down from my peak of about 235 or so around Jan 2014.)

I believe I’m now in what they call a “Fasted State”.  The feeling of being a bit hungry comes and goes – I’m finding it manageable at the moment.

I’m loving the idea that my body has sent my cells the message to “clean house” internally, via  autophagy.

I’m also loving the idea that:

  • Blood Sugar and Insulin are dropping
  • Insulin Resistance is dropping
  • Growth Hormone is rising

I tell myself that I want to try working out in this “Fasted State” to get the benefits described by Brad Pilon in Eat Stop Eat.

Update – 48 hours into fast:  worked out in a fasted state about 46 hours in, choosing to mostly do exercises that are not part of my regular “big five” program.  I wanted to signal my body to maintain my muscle mass and I think I accomplished that.  Mind feels sharp and clear – somewhat distracted by occasional hunger, but not too much.  Telling myself that what I’m doing is akin to the “cut” phase that bodybuilders often do before a competition.

Update – 58 hours into fast: slept well (88% score on sleep cycle app).  Feeling good.  Still have some hanging belly fat.  Considering the idea of committing to postponing eating until after I’ve completed certain personal goals (hell, I’ll admit it, I’ve been procrastinating at cleaning my office).  At the moment, I’m headed off to Pilates…

Update – 60 hours into fast: much improved flexibility and decent strength in a challenging Pilates class.   Weight now ~178, vs ~182 before.

Song: Double Lifetime

By jyoung / 2016-05-13

I love the way this song paints “the predicament” that mortal man finds himself in.

I especially appreciate this “making of” version of the song – it demonstrates how our first attempt (“practice run”) can lead to great improvements if we’re allowed to try again.  He proposes that we extend this lesson to a whole ‘nother lifetime!

I’ve just committed to performing this song (with the accompaniment of my dear wife Susan) at a gathering tomorrow evening – I’m excited to be taking this bold step, and look forward to more fun musical collaborations around this song!

This isn’t the first time Loudon Wainwright III has written on the theme of mortality:

Double Lifetime Lyrics (ready to print, as PDF)

I want a double lifetime, I wanna start over
One lifetime’s not enough, I need another
Sixty-four years on a practice run
Practice makes perfect, I’m about half done
I want a double lifetime

I want a double lifetime, I don’t wanna stuff it
Three score and ten just ain’t enough, it
Feels like I finally got it all figured out
Almost free from the shame and the doubt
I want a double lifetime

Yeah, a lot more time, that’s what I need
I can make my move, I can do the deed
I know I’m greedy, but what do I care
For the afterlife, I don’t wanna go there

I want a double lifetime, man I deserve it
I want it so bad, I even got the nerve
It’s gonna take to get down on my bended knees
Making prayers, saying pretty please
Give me a double lifetime

I want a double lifetime, I wasted my first one
The first time around, that’s always the worst one
You don’t know what you’re doing and you just can’t wait
You go ahead and do it and then it’s too late
You need a double lifetime

A lot of double life, in public and private
I wanna lead it again, I’m not gonna deny it
I’m just like you, it’s true, you know
Ask yourself: are you ready to go?
You want a double lifetime

Yeah a little more time ‘cause you know I never
Wanna keep living forever and ever
I know it sounds funny, and truth be told
But a hundred and don’t seem that old

I want a double lifetime, not gonna get it
But if a miracle happens, you know I’m gonna let it
If I eat enough yogurt, maybe I might
And the second time around, I’m gonna get it right
Gimme a double lifetime!

Eliminating Senescent Cells Radically Extends Lifespan of Mice

From http://www.agemarker.com/2016/02/scientists-can-now-radically-expand-the-lifespan-of-mice-and-humans-may-be-next/

Scientists Can Now Radically Expand the Lifespan of Mice—and Humans May Be Next

Posted by: on Feb 4, 2016 | No Comments

mouseWith a bit of clever genetic engineering, a team of scientists has just found an astonishing way to significantly expand the natural lifespan of mice. Now, at least one biotech company hopes to translate this breakthrough to fight aging in humans.

In a study published in the journal Nature, medical researchers at Mayo Clinic College of Medicine—led by cell biologists Darren Baker and Jan van Deursen—have made this decade’s biggest breakthrough in understanding the complex world of physical aging. The researchers found that systematically removing a category of living, stagnant cells (ones which can no longer reproduce) extends the lives of otherwise normal mice by 25 percent. Better yet, scouring these cells actually pushed back the process of aging, slowing the onset of various age-related illnesses like cataracts, heart and kidney deterioration, and even tumor formation.

“It’s not just that we’re making these mice live longer; they’re actually stay healthier longer too. That’s important, because if you were going to equate this to people, well, you don’t want to just extend the years of life that people are miserable or hospitalized,” says Baker.

The cells the scientists eliminated are called senescent cells. A senescent cell is an otherwise normal cell—say a skin or heart muscle cell—that has stopped dividing and reproducing. Right now, they’re found all over your body. Now, these cells have long been known to be associated with aging, “for example, in mice or people or monkeys, you find accumulations of these senescent cells over time and with age. And at sites of age-related disease, like osteoporosis, you’ll also find these cells,” says Baker. One theory behind why these cells exist in the first place is that hyper-stressed cells become senescent to prevent potentially cancerous, unfettered reproduction.

But until now, exactly what effect living senescent cells actually have on the body—either slowing aging, speeding it up, or not effecting the aging process at all—has largely been a mystery. But by leveraging modern techniques in genetic engineering, Baker and his colleagues finally set up an experiment that conclusively proved that the presence of senescent cells is largely a negative one. They shorten total lifespan and hasten the onset of age related illnesses, like cardiovascular disease.

Cellular Kill Switch

Although today’s paper is the result of many careful experiments painstakingly developed over a 7 year period, “the beauty of this study is that it’s actually really quite simple,” says Baker. The scientists took advantage of the fact that one hallmark of senescent cells is that they steadily secrete a certain tumor-suppressing protein molecule called “p16Ink4a.” We’ll call it p16, and you can think of it as basically their calling card.

By rewriting a tiny portion of the mouse genetic code, Baker and van Deursen’s team developed a genetic line of mice with cells that could, under the right circumstances, produce a powerful protein called caspase when they start secreting p16.  Caspase acts essentially as a self-destruct button; when it’s manufactured in a cell, that cell rapidly dies.

So what exactly are these circumstances where the p16 secreting cells start to create caspase and self-destruct? Well, only in the presence of a specific medicine the scientists could give the mice. With their highly-specific genetic tweak, the scientists had created a drug-initiated killswitch for senescent cells.

In today’s paper, Baker and van Deursen’s team reported what happened when the researchers turned on that killswitch in middle-aged mice, effectively scrubbing clean the mice of senescent cells. The medicine was injected into the genetically engineered mice’s bellies when they were 12 months old. (Keep in mind, the process isn’t perfect. Some senescent cells, including those found in the colon and liver managed to survive—possibly by avoiding the killswitch drug.)

The big takeaway is that “we saw about a 25 percent expansion of median lifespan of these mice. This held true for two different genetic strains of mice,” each engineered with the killswitch tweak, “and was irrespective of sex or the diet,” says Baker. These mice also showed delayed cancer onset, fewer cataracts, an increased drive to explore, and various other age-resistant effects in a wide range of body tissues. The body, it seems, is better off without senescent cells.

As far as the researchers could find, there was pretty much just a single downside of eliminating senescent cells: Wounds healed more slowly. That’s no big surprise, as senescent cells are known to play a role in healing and scar-tissue formation.

On To Humans?

Jesús Gil and Dominic Withers, two medical researchers at Imperial College London—who were not involved in today’s research—applaud today’s research and concur with the results. “The removal of senescent cells does indeed delay ageing and increase healthy lifespan,” they write in an essay accompanied alongside the research paper in the journal Nature.

So what’s next? Well, at the same time this paper was published, a company called Unity Biotechnology launched, with the stated goal to use this breakthrough understanding of senescent cells to develop medicines that fight the process of aging. (Obviously they’re going to have to use a different approach to genetically engineering humans.)

“Imagine drugs that could prevent and maybe even cure arthritis or heart disease or loss of eyesight. It’s an incredible aspiration,” said Nathaniel David, Ph.D., CEO of Unity Biotechnology in a press release. “If we can translate this biology into medicines, our children might grow up in a different world than we did. There will be many obstacles to overcome, but our team is committed and inspired to achieve our mission.”

– See more at: http://www.agemarker.com/2016/02/scientists-can-now-radically-expand-the-lifespan-of-mice-and-humans-may-be-next/#sthash.BBQe9DoU.dpuf

Telomeres Lengthened in Human Study

At last, a “gold standard” study showing Telomere Lengthening in Humans!

Full text of the study is here.

Dr Ed. Park summarizes the results:

At last, we have a well-designed study showing TA-65 lengthens telomeres in human subjects.

Salvador et al (Rejuvenation Research.2016 Mar 30]

This was a double-blinded (patients and researchers not aware what substance was taken), placebo-controlled (half were given ‘inactive’ substances), randomized controlled trial (assignment to treatment at two doses versus non-treatment was done randomly therefore minimizing the risk of unknown confounding variables).  The study was small but that is only a problem if you don’t find something. In this case, findings did reach statistical significance for the low dose TA-65 and control groups.

The study was conducted on 117 relatively healthy Barcelonian cytomegalovirus-positive subjects aged 53–87 years old.

23 subjects received one TA-65 capsule (250 U) and three placebo capsules;

22 subjects received four TA-65 capsules, each consisting of 250 U of TA-65 (i.e., 1000 U/4 capsules).

Fifty-two subjects received four placebo capsules. 

Here is a table highlighting the statistically-significantly findings:

ta-65_rct

As we can see, there was a decrease of 290 base pairs among the placebo group and an increase in 530 base pairs. Compared with the placebo group and assuming 100 base pair erosion per year (actually can vary a lot but 50-200 is typical), we can say that the low-dose TA-65 group GAINED SEVEN YEARS of viable telomere length.

My comments:  This is such great news!  At last, we have more than just in vitro and anecdotal evidence that we can lengthen our telomeres!

The study used TA-65 and the high quality Life Length telomere length test.  I’ve begun the process of contacting Isagenix about having them duplicate the test using their “Product B”, the only other commercially available natural product shown to activate telomerase in Sierra Sciences in vitro telomerase activation assay.

I judge that this new level of evidence for the previously thought to be impossible prospect of age reversal will be a “game changer” when it comes to helping people to consider the possibility of getting younger.

 

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