As I mentioned in an earlier post (1), most of us have the power (ignoring accidents and bad luck) to help preserve our health and extend our lives. How exactly can that be accomplished? Well, I’ve done some digging. (You never know what will happen when you send a 90-year-old brain to investigate a new subject, but I found information worth reporting.)

           Admittedly, the job wasn’t a walk in the park.  I quickly learned that scientists who study aging have set off a nuclear blast of information, the volume being so great that I could no more swallow it all than I could drink Lake Superior dry. So I’m going to tiptoe into this story and offer basic facts, and some speculation.

            You already know this, but I’m going to mention it anyway. Each of us, individually, is made up of humongous clusters of different cell types: brain cells , heart cells, lung cells, kidney cells, and many others. How many cells are tucked into one human body? The total number is of course impossible to count, but an average estimate suggests you are made up of about 30 trillion individual cells.

            I have trouble comprehending the enormity of such huge numbers. Do you? Here’s a little trick that seems to help. Consider each of your cells to be equal to one second. Then realize that one million seconds cover about 11.5 days. One billion seconds come and go about 32 years. And one trillion seconds? They stretch to more than 30,000 years. And don’t forget. We’re talking about 30 trillion cells, so multiply those numbers by 30.

            Cautionary note: whatever you do, please refrain from using this method when you think of our national debt, which now just happens to be over $30 trillion dollars. Ignoring this particular number may preserve your sanity. However, if that prodigious sum wedges uncomfortably into your mind, you might consider passing it on to certain senators and representatives who spend their time fumbling through chambers of our nation’s Capitol.

            To return to your trillions of cells, and this is important, each of those cells has a remarkable life of its own. Every cell, in a manner of speaking, does its own housekeeping. It buzzes with metabolic activity and even does its own recycling. Your cells work at a furious rate. For example, Yoshinori Ohsumi, a Nobel Prize winning scientist (I’ll come back to him), estimates that the millions of specialized cells in our bone marrow produce about 3 million red blood cells per second. (Circulating red cells decompose at the same rate.) To achieve this amazing production, those busy cells must also produce hemoglobin molecules (the ones carrying oxygen inside red blood cells) at a rate of 1 quadrillion molecules (10 to the 15 ^th power) per second. If that doesn’t boggle your mind, you’re not boggleable.

            One word that kept coming up when I dug into aging processes was autophagy (au‑’taf a‑jee), or it’s sometimes pronounced simply as each of its two basic components, auto + pha – gy (from Greek for self-devouring). The word coinage is usually attributed to Christian de Duve, who won a Nobel Prize in 1974 for his discovery of the lysosome, an amazing cell organelle now known to have more than 60 digestive enzymes within each one. Lysosomes accomplish fabulous deeds, as we shall see.

            Interest in autophagy skyrocketed after Nobel Laureate Yoshinori Ohsumi (first photo), managed to tease out its secrets and demonstrate that lysosomes were indeed the site of the cell’s recycling and renewal program. In this process the cells chop up damaged proteins, build new structures, revive mitochondria (our cell’s energy source), ward off infections, and maintain healthy metabolism. In short, autophagy recycles and renews the contents of our cells, which would not survive without that vital revival. Nor, of course, would we.

            Ohsumi’s work was thorough. He learned how autophagy works from start to finish, how it is controlled, and he even identified the key genes and molecules involved. Guess what. His experiments were done on, of all things, Baker’s yeast. (Never doubt the value of very basic research.) Autophagy later was shown to be present in human cells. Its activity is stimulated (up-regulated in genetic terms) by a number of stresses such as fasting and exercise, along with other stresses to be mentioned in later posts.

            Let’s focus for a moment on fasting. It’s long been known that severe dietary restriction extends the lives of rodents (2), and it is believed that autophagy contributes to the extended the life spans of underfed animals.

            As I began looking into all of this, I kept running into accolades for so-called intermittent fasting as a method of promoting autophagy. As you may know, intermittent fasting, a method often used for weight loss, comes in a number of variations. For example, the so-called 16/8 routine requires you fast for 16 hours and consume all of your meals within an 8 hour window (or slightly modified to 18/6). There’s also the 5/2 regimen, in which you eat normally for five days of the week and “fast” (either completely or maybe consuming only 500 calories on those days), and there are other modifications.  I started the 16/8 routine a week ago, ending my dinner by 8 p.m. and consuming nothing but water and black coffee in the morning, finally breaking my fast at noon.

            The routine wasn’t difficult for me, maybe because years ago in my laboratory, my colleagues and I fasted at times for 24 hours (this was required while performing certain experiments on ourselves). I quickly discovered those 24-hour fasts weren’t difficult to accomplish if I just refused to consider other options. I had that same mind-set this week and did just fine.

            So did I push my autophagy button and begin stretching my earthly days? I wish I knew the answer. I started my program optimistically, but during this week as I searched for definitive information, I found no concrete data demonstrating that a 16 hour fast provides adequate time to induce autophagy. (There are plenty sources claiming it does, but I found no convincing data to document that assertion.)

            I did find one review of the scientific literature (it was published just a few months ago (3) that echoed my skepticism. Here’s part of the abstract from that extensive review.  There is significant interest in the body of literature describing longitudinal adaptations to IF (intermittent fasting). Less attention has been given to the acute physiological responses that occur during the fasting durations that are commonly employed by IF practitioners. Thus, the purpose of this review was to examine the physiological responses – including alterations in substrate metabolism, systemic hormones, and autophagy – that occur throughout an acute fast. Literature searches were performed to locate relevant research describing physiological responses to acute fasting and short‑term starvation. A single fast demonstrated the ability to alter glucose and lipid metabolism within the initial 24 hours (indicating a shift to ketosis, my words), but variations in protein metabolism appeared to be minimal within this time frame. The ability of an acute fast to elicit significant increases in autophagy is still unknown. (I increased the font size of the previous sentence for emphasis.)

            To be clear, the conclusion of the authors bothers me not at all. First of all, extended periods of fasting (longer that the “acute fast” of 24 hours mentioned above) clearly unleash autophagy, as do other stresses that I will come to in later posts.  And intermittent fasting may well be effective in weight reduction, but that’s not the focus of my search. I’m centered here on factors that extend healthy lives, and on the variety of stimuli that trigger autophagy, along with other encouraging developments that promise to preserve our health and extend our lives. I’ll noodle around this area for a while, and I intend to come up with more reports. Stay tuned.

     Would you like to live for, say, 110 years?  Does a long life appeal to you? Is it even possible to achieve? Seemingly so. Present-day science is oozing with promises to extend our lives.  How would I answer my opening question? That depends. If I were able to survive for well over 100 years feeling as healthy and happy as I am now, I’d shout “You betcha!”

     A quick disclaimer: I have not a shred of expertise on aging (other than reaching 90, which merely triggered my curiosity), so an authority I am not. But I’ve nosed around to see what’s going on with those who are devoted to studying our aging processes. A lot is going on! Facts jumped out at me from all directions. Those dedicated scientists, bless their hearts, have learned enough to fill a good scattering of scientific journals. And what they’ve discovered is good news for practically everyone.

     For one thing, the thousands of experts who study how we age seem to come together on one important point, namely this. Aging is a decidedly plastic process. It is influenced by a myriad of factors, a good number of which we can influence.

     Here’s one collaborating statement that comes from David Sinclair (1), professor of genetics and co-director of a center for aging research at Harvard medical school. What he said shocked me. I didn’t scribble it down as I heard it, so what follows is a paraphrase, but the gist of it was this: 80% of our rate of aging and our health when older is determined by “environmental” (lifestyle?) factors; only 20% is determined by our genome. Wow! Did that snap your eyes open? The evidence backing this statement appears to be solid, and it comes from many sources. What we do through the years is more important than what our genes control. In short, we can live better, and live longer, by adjusting our daily routines.

     Controlling our destiny isn’t all new stuff, of course. We’ve known for years that certain habits are bad for us. Smoking is a prime example. The smoke messes up lungs and hearts, among other organs. An article in the New England Journal of Medicine a few years ago ticked off more than a dozen disease processes set into play or aggravated by smoking.

     But here we’re talking about good habits. The more recent information concerning our aging, exciting as it is, has been derived largely by untangling rather complex intracellular biochemical pathways, and by digging into intricate genetic mechanisms, but luckily we don’t have to understand all of the complex details to realize what it all means, and to use it to our advantage.

     The basic message could not be clearer if it were announced in huge, glowing neon letters. And it is very simple. We have the power (ignoring accidents and bad luck) to slow our “aging,” and to remain healthier longer as we move through the years. This can be accomplished by adjusting our lifestyles (such as walking more, and weight lifting), by dietary alterations (so-called intermittent fasting), by taking certain oral supplements, and even by more experimental and less-available (and less generally accepted) genetic manipulations.

     I’ll focus on this theme for a couple of posts. Next time I’ll examine the varying methods of intermittent fasting, an accepted method for prolonging life and preserving health. I’ll even touch lightly on how that approach does the trick to slow down our aging process.

IMPORTANT HOUSEKEEPING NOTE REGARDING THE COLORS OF MEDICINE.

     For those of you reading my installments of The Colors of Medicine, I have news. Starting tomorrow (February 1),  you will be able to download the complete Kindle version of my novel from Amazon.com at no cost.  I’m giving it away free for the first five days in February. I must say it has been fun for me to provide little teasers at the beginning of each installment published here (number 13 was posted yesterday) and I plan to put out one final installment here tomorrow, along with a brief teaser indicating that the story is about to make a rather abrupt transition.  I’ll provide more details when I post installment 14.

            Having flown into my tenth decade with some speed, and finding I enjoy the altitude (1), I’ve begun ruminating about getting old. Why, I’ve wondered, have I beaten the odds? Today I’m going to retrace my tracks.  Next time I’ll look at the amazing process of aging itself.

            What was it that allowed me to survive longer than the average male born in 1932? The glib answer, of course, is luck. Dame Fortune has indeed smiled on me, at least in my later years. But what was it that actually kept my blood flowing, and my lungs going, for nine decades? Genetics and lifestyle likely entered in, but so did modern medicine, a big factor as I shall describe.

            In 2001, I noticed something new, a mild sensation beneath my collar bone as I walked up my favorite long hill. It wasn’t pain, just something odd. My medical training led me to suspect it was angina pectoris. A quick visit to a well-organized cardiac catheterization laboratory confirmed my suspicion. (One of my dye-filled coronary arteries was significantly narrowed.) I returned to the same laboratory on the next day, and stents were inserted and expanded in that narrowed segment (2). Presto! Normal blood flow to my heart was restored. No more odd feelings when I tramped up hills.

            Since then, for over two decades, my cardiac pump has been a model of efficiency. It chugs merrily along without a hint of discomfort. Good timing on my part! Stents had been available for only about a decade (3) when I needed mine, those being much improved from earlier versions. Thankfully, those tiny gadgets have kept my important coronary artery nicely open. Without their silent and persistent help, I might well have suffered a heart attack years ago.

            Here’s more about my circulation. During my forties, fifties, and sixties, the electrical components of my heart were cranky. At times they fired off extra beats like a wild drummer. The wild beats by themselves weren’t especially worrisome, but occasionally the electrical noise turned completely rowdy and pitched my atria into brief bursts of fibrillation.

            You probably know this, but I’ll mention it anyway. The heart still can pump blood quite effectively when its two upper chambers are fibrillating, but with the atria just quivering during fibrillation, rather than contracting normally, blood sometimes clots in their appendages. Those clots may break loose and thumb a ride in arterial blood (as an embolus) to the brain, or other organs, thus plugging up a small artery and causing a stroke, or other damage.

            I had a couple of minor versions of a stroke, those called transient ischemic attacks, in which I lost partial sight in one eye for just a couple of minutes. Again, thanks to my earlier training, I was pretty sure what was going on, and the spots showing up in my brain in more recent CAT scans and MRI screens seem to bear that out.

            Even with my relatively small risk of going into atrial fibrillation, I now take an oral anticoagulant, a blood thinner if you prefer, to minimize clot formation should I happen to slip into fibrillation again. The drug I take is effective and has relatively few side effects. It was approved for use only a couple of years ago, another example of lucky timing on my part.

            I’ve also had a few skin cancers, basal cell types that almost never metastasize, and a squamous cell type that usually metastasize late, every one skillfully excised surgically, or frozen off, and all thus cured. I also developed a deeper cancer four years ago, a tumor treated with high-intensity radiation. From all indications that therapy, also quite new and even revolutionary, routed my cancer completely.

            Quick summary. Without the above medical care, my way to 90 would have been bumpier, or knocked entirely off track by one problem or another, reason enough for me to honor the many men and women who made those marvelous advances possible. Thanks to all of this progress, I seem to be ticking along just fine, and feeling great!

            Finally, I must give myself a bit of credit too. Keeping active surely was a plus. I’ve always enjoyed keeping my bones in motion. I played tennis until I had a knee replaced (another great intervention that has lifted my life tremendously, and one not available when I was younger). I still walk extra miles and mess with weights. It’s well established that physical exercise turns on good genes, so I’m confident my gene pool benefits from my activity.  A good reason for me to keep at it! And for you too!

            Next time I’ll nose into the science of aging. You’ll be amazed by all that’s going on.