Ideology is Holding Back Aging Research

We can all agree that priorities in research for a longer, healthier human life span are far from rational.  Among the distorting influences are

  • Leap-frogging ahead to medical research in a field where the basic science is not yet fully understood.
  • Inertia from a research infrastructure that has been built on the wrong priorities.  Both people applying for grants and people evaluating those applications are stuck in an old paradigm.
  • Investment capital seeks profits in short-term, low risk projects
  • Misunderstanding of the basic nature of aging—a misunderstanding which also has capitalist roots.

Last month, an article in Nature Biotech surveyed the firms that are involved in longevity research, their resources and their strategies.


Until recently, research in aging medicine has been Balkanized into study of atherosclerosis, cancer, Alzheimer’s disease, Parkinson’s, and various smaller projects to study the diseases that affect older people.  The idea that we might be able to address all these diseases in one fell swoop if we can alter the fundamental biology of aging is not new, but it has been slow to take hold, and even now, research priorities remain lopsided.  Basic research in the biology of aging is absurdly under-funded, when compared to budgets for research on particular diseases.  The National Cancer Inst alone has a $5 billion budget, and Big Pharma is investing billions of their own in new chemotherapy agents that may or may not be marginally more effective than the old.  Meanwhile, the basic science of aging is studied on a budget estimated to be less than $1 billion.  Within that budget for the pure science of aging, I would propose that there are also substantially distorted priorities.

An article in Nature Biotech last month surveyed the private biotech investments in anti-aging technology.  We should all pause to celebrate the fact that this field finally has credibility, and is attracting substantial funding.  But, in my view, the funding is largely misdirected, and a few projects that I think would be good bets for a major leap in life extension have yet to be funded at all.

Researchers on aging are slowly pivoting from treating aging as a disease or indication to considering it a collection of age-related diseases.

This is the good news.  There is an enormous streamlining available when we turn from treating diseases separately to treating the root cause of aging.  But there is still a lot of ideology that says, “it can’t be that easy.”  This is the bad news.

[Linda] Partridge says “theoretical and practical insights have led to the conclusion that aging is likely to be a highly polygenic trait”. Contributing to aging is a protean list of processes, among them, genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication.

Partridge’s theory is taken from George Williams’s seminal paper of 1957.  He writes in response to Medawar’s program of isolating the root causes of aging in a small number of physiological processes:

Any such small number of primary physiological factors is a logical impossibility if the assumptions made in the present study are valid. This conclusion banishes the “fountain of youth” to the limbo of scientific impossibilities where other human aspirations, like the perpetual motion machine and Laplace’s “superman” have already been placed by other theoretical considerations. Such conclusions are always disappointing, but they have the desirable consequence of channeling research in directions that are likely to be fruitful.  [Williams, 1957]

But this perfectly reasonable conjecture of Williams was proven to be dead wrong in the 1990s, as single genes were discovered that offered dramatic life extension in worms.  There are now dozens of such genes known, and many of them are genes that need to be disabled, not new genes that need to be added to the genome.  In other words, there are powerful, known pro-aging mechanisms that make promising targets for pharmaceutical intervention.  Throwing a monkey wrench into an existing metabolic pathway is what Big Pharma knows best how to do (e.g., seratonin re-uptake inhibitors, beta blockers, COX2 inhibitors).  What we need is an inhibitor of pro-aging genes.

Rapamycin seems to be the first candidate in this category, and it is being appropriately explored, as reported in this space last week.

Here’s a caveat: The easiest path to life extension is through caloric restriction mimetics.  In other words, trick the body into thinking it has less food than it is really eating.  Some of the early genetic modifications in worms worked in this way.  DAF-2 was an early discovery, doubling life span of worms in Kenyon’s lab when it was partially disabled [1993].  The catch is that lab worms are champions of adjustable life span.  They are exquisitely adapted to be able to survive months at a time with no food at all, but to die within a few days once they have plenty to eat.  Larger animals also live longer when they eat less, but the effect is much smaller.  My guess is that CR potentially adds 5-10 years to human life span–nothing to sneeze at, but not the big, dramatic gains we might hope for in the long run.  If we find a really, really good caloric restriction mimetic, we might hope to capture most of that 5-10 years.

This is the low-hanging fruit being chased by the lion’s share of private investment in anti-aging medicine today.  No doubt, it will be achieved in short order (though it may be decades before we know which strategy works best, because longevity data in humans takes a long time to compile.)

Neglected is the potential for much greater gains that go beyond the potential of CR mimetics.

Let’s go back to Partridge’s “protean list” of complicated processes that have to be addressed:

  1. telomere attrition — This is a primary aging clock, cause of many downstream effects.
  2. epigenetic alterations — Gene expression changes with age.  When we are in our teens, gene expression is modified to halt growth and initiate puberty.  When we get old, a similar process leads to a gene expression profile that gradually destroys the body on an accelerating schedule.
  3. genomic instability — This is DNA damage, and by far the greatest source comes from short telomeres.  Telomeres cap the ends of a chromosome and keep it from unraveling.  When the telomere is too short, the chromosome becomes unstable.  So this may be traceable to #1. => See comment below by Bowles for another mode of genomic instability, this one controlled by epigenetic markers.
  4. loss of proteostasis — This refers to protein mis-folding, which is observed in Alzheimer’s Disease among other diseases of old age.  But proteins are being created and folded and re-cycled all the time.  Part of the reason that mis-folded proteins accumulate with age is simply that the body’s repair mechanisms are slowing down.  Another part is (my guess) that genes that take care of this function are being down-regulated–in other words, we might trace this problem to #2 as primary cause.
  5. deregulated nutrient-sensing — This is loss of response to insulin, related to “metabolic syndrome.”  I believe this happens under epigenetic control.
  6. mitochondrial dysfunction — This is the “free radical theory” or “mitochondrial free radical theory”, still invoked despite all the evidence against it.  It’s true that we have fewer mitochondria as we age, and that the mitochondria process energy less efficiently.  But the activity and the reproduction of mitochondria are under control of the cell nucleus, hence this, too, will prove to be a symptom and not a root cause of aging.
  7. cellular senescence — barely distinguishable from #1, telomere attrition.
  8. stem cell exhaustion — primarily caused by telomere attrition.
  9. altered intercellular communication — hormone signals through the blood are under epigenetic control.

Thus the “protean list” of nine complications derive largely from two ultimate sources: telomere loss and epigenetic reprogramming.  These should be our primary targets for anti-aging research.

* A Cell article this week from Elizabeth Blackburn’s UCSF lab suggests that activating telomerase may have rejuvenating benefits over and above its role in extending telomeres.

Companies investing in anti-aging research

The following table is taken from the same article: 

Table 1 Companies commercializing longevity
Company (year founded, location)FocusFounders (affiliation)Seminal publication
Alkahest (2014)Translating parabiosis, transfusing young blood into Alzheimer’s patientsKaroly Nikolich, Tony Wyss- CorayVilleda 2014
Calico (California Life Company, 2013)Research and development into the biology of life span with undisclosed amount of Google funding.Arthur Levinson, Cynthia Kenyon, David Botstein, Hal Barron
CohBar (2009, Pasadena, CA, USA)Develops mitochondria-derived peptides with pleiotropic effects in age-related conditions (diabetes, cardiovascular disease, Alzheimer’s disease)Pinchas Cohen (University of Southern California), Nir Barzilai (Albert Einstein), John Amatruda (formerly with Merck), David SinclairMuzumdar, 2009
Elysium Health (2014)Consumer health productsLeonard Guarente (MIT)Mouchiroud 2013
Human Longevity Inc (2014)Combining human genomics, infor­matics, stem cell advances to solve diseases of agingCraig Venter, Robert Hariri, Peter Diamandis
L-Nutra (2008)Fasting mimicking and enhancing dietsValter Longo (USC)Parrella 2013
Metrobiotech (2008)Compounds that raise NAD+ levelsDavid Sinclair (Harvard)Gomes 2013
Navitor Pharmaceuticals (2014)Selective regulation of M-TORC1, raised $23.5 million in series A round of fundingDavid Sabatini (MIT/ Harvard)Dibble 2013
Proteostasis Therapeutics (2008)Therapeutics that modulate protein folding and homeostasis; preclinical programs in cystic fibrosis, neurode­generative diseases $45M raisedAndrew Dillin (UC Berkeley) and Jeffrey Kelly (Scripps Research Institute)Cohen 2009

 

None of these is investigating epigenetic reprogramming, probably because it is too early for commercial investment–no one knows how to do it yet.  The only company based on telomerase activation is Sierra Sciences, which is below the part of the chart I reproduced, companies listed as in financial straits.  The only company with research based on a changing profile of circulating blood factors is the first, Alkahest.

The two wild cards are Craig Venter’s Human Longevity, Inc and Google’s CALICO.  Both are well funded, and neither has offered details about their research programs.  Last year, Venter hired the man who headed Google Translate, signaling a brute force approach, based on theoretical agnosticism: Sequence a million human genomes.  Look for patterns, e.g., what do the genomes of people who don’t get Alzheimer’s Disease have in common.  In my opinion, this is a cumbersome approach, inspired by successes in information processing, rather than knowledge of biology.  As I said, I think aging is controlled by epigenetics, and the largest gains will be made when we learn to re-program the epigenetic profile of an old person to make it look more like a young person.

CALICO, then, is crucial.  Their direction is not yet determined, and will be shaped by Kenyon’s vision and beliefs.  Kenyon has ambition and a wide-open imagination, and she is open to ideas about programmed aging.  We can hope that her extensive experience with worms informs but does not limit her vision.

 

Foundation funding

Historically, Ellison Foundation has been one of the most reliable sources of big bucks for innovative research, with about $400 million in aging-related grants since 1997.  But last year, Ellison pulled out of anti-aging research.  The Life Extension Foundation (LEF.org) has, by its own accounting, funded research totaling $140 million over three decades.  They have been independent of the bureaucratic thinking of the National Institutes, but they have their own biases, favoring natural remedies that can be sold without FDA approval.  SENS Foundation, with an annual budget of $4.5M, has grown from the singular vision of Aubrey de Grey, and has all the ambition and also the limitations of Aubrey’s paradigm.  To their credit, SENS is looking seriously at long-term projects that show potential for major gains in life span.  But, at least from my perspective, they are neglecting the most promising avenues, because Aubrey does not believe it is possible that aging might  be controlled by biochemical signaling.  The “engineering” approach to fixing what goes wrong is a long, hard road.  Peter Thiel has offered the greatest outside support for SENS, and Thiel has also made grants to other anti-aging initiatives.

 

Historical distortion of aging science by evolutionary theory

 In the long run, the greatest damage has been done indirectly, by capitalist ideology that has infiltrated the culture of evolutionary science.  From the beginning, Darwin’s theory was hijacked by “social Darwinism” which twisted the theory to create justification for hereditary class privilege in British society.  “Fitness” was elided with “financial success”.  “Natural selection” became a sanction from Natural Law for income inequality.

In the first half of the 20th Century, Darwin’s theory was re-cast as a modern science, with quantitative measures, equations, and predictions.  The work was spearheaded by R.A. Fisher, who happened to be both a prodigious genius in statistical theory, and also an elitist/eugenicist.  The version of evolutionary theory that was bequeathed to us was further caricatured by Richard Dawkins as the Selfish Gene.  In this version of evolution, the emphasis is on individual competition to the exclusion of cooperation.  There is little room for self-sacrifice, and such obviously communal adaptations as sexual reproduction have become inscrutable mysteries.

This kind of theoretical foundation has made the biological community blind to clear and manifest signs that aging is an epigenetic program, akin to growth and deveopment.  When you are a teenager, genes are turned on that cause secretions of sex hormones, and reproductive function is awakened.  When you are in your 60s and after, another set of hormones is switched on epigenetically, and the body becomes hyper-inflamed, auto-immune, insulin resistant and self-destructive.  Most biologists look at these changes and they figure that the body must know what it is doing, that there must be a redeeming positive benefit for these changes, and it would be dangerous to second-guess the body’s wisdom.  But the truth is that these late-life epigenetic changes have little benefit, and their predominant purpose is to destroy the body on an accelerating time scale.

Most researchers are busy asking themselves what goes wrong.  Neglected is the process plain and clear, where the body is being destroyed by “what goes right”.

It follows that the greatest opportunities for radical anti-aging are to characterize the chemical signals that control aging, and to adjust the signaling environment of an old body to make it more like a young body.

To some extent, this can be accomplished simply by lengthening telomeres, which have a substantial epigenetic reach of their own (TPE).  There are knowledgable advocates in the field who think lengthening telomeres is the most important thing we can do.  It is certainly the most accessible path, and should be a high near-term research priority.

 

My candidate for basic research:
Study the Epigenetic Clock that Controls Development as well as Aging

Biological science today does not know how the onset of puberty is timed.  We know that epigenetic changes are triggered at an appropriate age, and a few key sex hormones initiate the onset of fertility.  What we don’t know is how the body detects that the time has come for this to happen, whether there is an internal clock mechanism, and if so, how it works.  To me, this would be one of the most valuable studies in basic science, and I believe that when the epigenetic/developmental clock is understood, the results will carry over directly to understanding of the aging clock.  And if we can reset the aging clock, it’s a whole new ballgame.

Anti-Aging Pills in the News

Last week Len Guarente announced his company will be selling a proprietary formula based on NR, the NADH precursor.  This week, there’s an article about a project at Novartis to make a safe anti-aging pill from rapamycin.  I’m more excited by the latter than the former.

drawing by Maddy Ballard

drawing by Maddy Ballard

 

An MIT Lab offers NADH plus Blueberries

Several readers have asked my comments on the Guarente formula, being sold through Elysium Health.  Len Guarente is a solid, innovative scientist who has contributed a lot to our field and trained several students who went on to make substantial contributions of their own.  He’s also an honest guy, with his heart in the right place.

The formula he plans to sell consists of Nicotinamide Riboside and pterostilbene.  I wrote about NR a in November.  I’m not convinced.  It’s just too easy to extend life span in worms and flies–much more difficult in mice and people.  I have see no data on NR and life span in mice.  The most promising results I have seen show that NR slows progression of Alzheimer’s Disease in mice that are genetically engineered to be susceptible to AD [ref].

Pterostilbene has a chemical structure similar to resveratrol, and it is thought to be one of the beneficial components in blueberries.

Pterostilbene shows the same kind of benefit as NR in the mouse model of Alzheimer’s [ref], but it does not extend life span of outbred mice [ref].

The press release about the Elysium product claims that there is an expected synergy between NADH and pterostilbene.  Len knows a lot more than I do about genetics and biochemistry, and I’m inclined to give him the benefit of the doubt.  But I don’t think that theory about the biochemistry of aging is in any shape that we should rely on it without direct evidence, and I look for that evidence in mammals.

 

Rapamycin from Novartis

There’s an article from Bloomberg today about research at Novartis toward an anti-aging drug based on rapamycin.  Rapamycin has the opposite issues from the Elysium product.  It works great extending life span in rodents, but it is a powerful drug that may have too many side effects to be considered for general use by people who aren’t sick.  It’s also prohibitively expensive for most of us, though it is not as difficult to get as it was a few years ago when the dramatic effect on mice was first announced in Nature.

The reason rapamycin is scary is that its primary use is as a powerful immune suppressant, preventing rejection by people who are receiving organ transplants.  If rapamycin makes the immune system tolerates someone else’s kidney (so the reasoning goes), what else will it tolerate?  Cancer cells?  Invading viruses?  Herpes?  The Bloomberg article hints that rapamycin may be more selective than that, and there is at least one study which seems to show that a drug acting on the Target of Rapamycin (TOR) can enhance the immune response as well as suppressing it.

Novartis is not trying to market rapamycin, but to look for variants that might have the same benefit without the side effects.

The article mentions Mikhail Blagosklonny as a prominent researcher who has enough faith in rapamycin to take it himself. He has written an article making the case that it acts directly on the core of the aging metabolism. It really does slow aging.

“Some people ask me, is it dangerous to take rapamycin?” Blagosklonny says. “It’s more dangerous to not take rapamycin than to overeat, smoke, and drive without belt, taken together.”

For counterpoint, the Bloomberg article quotes Valter Longo,

“Rapamycin works on pathways that are too fundamental to normal cellular function to be used as a drug in healthy people until we have much more safety data,” says Valter Longo, a professor at the University of Southern California who discovered key pathways related to TOR. He points out that periodic fasting also shuts down the same pathways, without the side effects.

This same Bloomberg article mentions a claim by Brian Kennedy that metformin lowers mortality in diabetics so well that it’s actually 15% below mortality rates in age-matched non-diabetics [ref].  This is a remarkable finding, the best we can hope for, since there are no long-term data on effects of metformin for people who are not diabetic. It contradicts several meta-studies [ref, ref] that find no net mortality benefit for metformin.  (I think that the balance of evidence favors metformin, and I take it myself. If you are overweight or leaning to high blood sugar, you might consider it.)

 

The Bottom Line

We are at a stage in the science where there is much promise and little certainty.  How do we decide when to take a chance and what to take a chance on?  All the scientific data are still only half the input; the other half is in each of us as individuals.  There is a reason there is so much scatter in the statistics, and even inconsistency from one study to the next.  We are all unique individuals, both in how our metabolisms respond to drugs, and in what we want out of life.  We may try to choose a strategy for the long haul, but if a treatment helps us feel more energetic or more alive or better balanced in the short run, that is and should be a part of the choice that we make.  I have written about my experience with low-dose deprenyl, which I take for life extension, but which also loosens my inhibitions a bit in a way that I appreciate.

A part of the calculus which is rarely discussed is our stage in life.  The older we are (and the worse our health), the more inclined to take a risk on some treatment that may be our last best hope.  I am 65 and can still hike all day, but I may have run my last marathon.  I attend to the changes in my body from year to year, and I am willing to take some risks to slow down the loss.  My friend, Stan, still works long hours at two psychiatry clinics at 86, and dances on the weekends.  He is more willing than I to take a flier on a new idea.  I hear rumors about 90-year-old tycoons who…but they are only rumors.

I am saddened when a prominent member of the anti-aging community consents to request for treatment with Lupron by his 12-year-old son.  Lupron blocks testosterone and delays puberty.  The boy should know that he will have far better options for a long and healthy life as science continues to progress.  I tell my daughters, in their 20s, to take good care of themselves and plan for a life of 200 years.  In the near future, aging may no longer be the dominant risk to our health and wellbeing. I am more confident that tomorrow’s technology will be there to delay aging for our children than I am in our collective ability to deliver to them intact ecosystems that support human life.


 

Visomitin Eye Drops — a Personal Follow-up

Last year, I wrote about a product developed by Vladimir Skulachev, veteran biochemist at Moscow State University, that targets Coenzyme Q to the mitochondria.  It is available as eye drops, which in lab studies have brought horses and dogs back from the brink of blindness. (A closely-related molecule is available in pill form and as a cosmetic from Mito-Q, New Zealand.)

I have been taking Visomitin eye drops for a year and a half, and had an eye exam at the start of this period, and again this week.  Results of the two eye exams were just about the same. Perhaps the beginnings of yellowing of the lens, an early stage of cataracts.  I am fortunate to have eyes that focus well at mid-range (slightly myopic), so I still am comfortable without glasses most of the time.  But over this year, I noticed that there are more times when I reach for reading glasses.

If any readers have personal experiences to share with Visomitin, with Metformin or with Rapamycin, I hope you will comment below.

Do we really need epidemiology to tell us to get off our duffs?

The meme we hear in the news is that sedentary time, time spent sitting, is bad for us. I started out researching this week’s blog on inactivity, and ended up thinking about how to keep aspirations high and stay engaged with community.

Last week, the largest meta-analysis to date of inactivity was reported in the popular science press [for example]. The message is that even for people who exercise vigorously for part of each day, sitting still for long periods during the rest of the day poses an independent health risk. I found that evidence for this interpretation is weak. There is stronger evidence for the harm caused by sedentary behavior at the other end of the spectrum, for people who get little or no exercise.

I’ve been thinking about what that means, how “inactivity” is measured, and what we can do to avoid it.  I’m leaning toward the conclusion that getting up and moving frequently is good for us as part of a general program to avoid tunnel vision, to improve well-being and creativity even though the “independent mortality risk” is likely to be lost in the noise.

For people who don’t exercise at all, David Alter and colleagues at U of Toronto found a significant 46% additional mortality risk from too much time spent sitting.  But combining the statistical power of 41 separate studies, they found only an insignificant 16% added mortality risk for those with a vigorous exercise program.  In context 16% is not a lot–and here it was not statistically distinguishable from zero.  The failure of statistical significance in this case is not for lack of numbers, but because the different studies produced inconsistent results.

The reason 16% must be regarded as small is that all the different studies attempted to extract information about sedentary behavior from a diverse group of people who differed in many other ways. The statistical tool for separating out different causal factors is called “multivariate regression,” and it works reliably with 2 or 3 variables, but beyond this number, the statistical power is overwhelmed by the exponentially growing number of ways in which the different variables can interact.

Here’s what I mean (applied to the present case): All the studies here compiled were seeking information about time spent sitting, and how it might contribute to risk of mortality and disease. But the people being interviewed differed in many other ways as well, ways which had far more powerful effects on mortality risk than the time spent sitting. So for the study to produce meaningful results, it must disentangle such things as diet, obesity, exercise, family and social support, depression, and psychological passivity.

The researchers aren’t so dumb, so each of the studies that are included in this meta-analysis controls for just 2 or 3 other variables.  But these variables differ from one study to the next, making it hard for Alter and his team to draw meaningful generalizations.

Almost all these studies rely on self-reporting, which is notoriously inaccurate.  People are reluctant to admit how passive they are, and they are likely to be dishonest with themselves, let alone an anonymous researcher. The “good” response was supposed to be when people report less than 8 hours of sitting in a day. But what does this mean in a culture where our “society is engineered, physically and socially, to be sitting-centric.” [quote ref] Are these people who have jobs as sales clerks where they are on their feet all day, as opposed to desk jobs? Or are they just failing to mentally aggregate the time spent in a car, at a desk, at the kitchen table, and in front of the TV?

Translating the results into behavior change recommendations is also problematic.  The most obvious and frequently-recommended remedy is to get up from sitting, say once or twice in an hour, for some activity that gets the blood flowing.  But exactly none of the studies compared people who do this with people who sit through without getting up.  The questionnaires only asked about total time spent sitting.  We must take it on faith that briefly interrupting the sedentary period has benefits out of proportion to the time invested.

Though this is an article of faith (or theory – which is but another name for faith), I’m inclined to extend my faith in this direction.  In my own experience, while I’m reading or writing, I’m either pleasantly engaged in what I’m doing, or I’m in a stupor.  Either way, getting up to do something vigorous for a few minutes doesn’t seem at all appealing. But when I make the effort, it almost always invigorates me.  I come back, not just more alert, but often with a fresh idea or a change in my reference frame.

So I recommend taking 1 minute out of each hour for vigorous exercise, though I admit to finding this difficult myself. Getting up to think and walk is also something I can recommend from personal experience. The treadmill desk is something with which I have only vicarious experience.

 

Physical Passivity and Mental Passivity

About a third of the studies asked not about “time spent sitting” but about “time watching TV”.  In fact, TV has proven to be a robust predictor of mortality, with a clearer signal than the current emphasis on “sitting”.  Among the many studies in Alter’s meta-analysis, some of the largest effects came from those designed to study TV time, not sitting time.

Is there a difference between sitting behind a desk writing poetry, and sitting in front of a TV watching a program you don’t particularly like?  Emotional factors in mortality risk are huge, and depression is right up there.  Those who feel helpless and hopeless have far higher mortality risk than those who feel empowered, useful, and pro-active in their daily lives.

Watching TV brings on a dead state of mind for many people in our culture, who are numb while being passively entertained.  The relative risk for TV watching is far higher than the general risk of “sedentary behavior.” [ref].  Is mental passivity even worse than physical passivity?

In epidemiology and longevity studies, we have paid more attention to physilogical than to psychological variables, but psychology is at least as important. What is more, the physical and the mental are often difficult to disentangle, and there are other reasons to pay attention to the state of our wellbeing and empowerment and general satisfaction with life, even if there weren’t huge longevity benefits.

Depression is a huge risk factor for mortality–larger than obesity and sedentary life style combined.  Depression raises the risk of mortality by a factor of 3.1 for men, 1.7 for women [ref, ref].  For comparison, obesity (BMI>35) increases mortality by a factor 1.3 [ref]. Lack of exercise is associated with a similar risk factor of 1.3 in men and 1.4 in women [ref].

What is depression? I invite your comments on the subject.  I am convinced that depression is more a cultural than a psychological disease.  There are some countries in which depression is virtually unknown.  I think of depression as a lack of affect, a helplessness and detachment, a feeling that nothing I can do matters.  I imagine that the state of the American economy and politics contribute to feelings of isolation, disempowerment and hopelessness.

There is “clinical”, incapacitating depression that has afflicted people close to me.  Less extreme, there is walking through life like a zombie, afraid to feel and to act, unmotivated to change, unsure that anything that we do matters.  I have been there.  Closer to “normal” on the continuum, there is a general damping of the sense of wonder and zest for life that are our birthright.  Leaving this birthright behind, or at least putting it aside, seems to be a pre-condition for normal participation in work and social activities, (especially for white folks).  A video from The Onion helps me laugh about it.

From sedentary to television, from television to depression, from depression to powerlessness–these connections are my own, and I can’t claim the authority of science.  But I think they’re legitimate parts of the discussion if we’re looking for solutions that offer us more fulfilling lives on the way to health and longevity.  I welcome your perspectives in the comment section.

 

It doesn’t matter if I’m feeling blah,
just so long as I’m not clinically depressed

Many of us in Western capitalist cultures not only have vague feelings of powerlessness, but we tend to feel powerless about our powerlessness.  We don’t want to think about it because there would seem to be nothing we can do about it. We don’t want to be stigmatized as a whiner, let alone as a psychiatric patient.

But the excesses of capitalism and the humdrum lives into which we are forced by economic conditions have profound effects on our wellbeing and also our longevity.  In other words, it’s not just that clinical depression has a huge effect on your health; the “subclinical” version that is so familiar to most of us is also harmful.  This is an understudied effect, because sublinical depression is the norm–what do you measure it against?  This week, another study from U of Toronto gave us a hint at how the subject can be approached.

Researchers have linked positive emotions–especially the awe we feel when touched by the beauty of nature, art and spirituality–with lower levels of pro-inflammatory cytokines, which are proteins that signal the immune system to work harder.

“Our findings demonstrate that positive emotions are associated with the markers of good health,” said Jennifer Stellar, a postdoctoral researcher at the University of Toronto and lead author of the study, which she conducted while at UC Berkeley. [Science Daily]

Interpolating between studies of depression and studies of inspired joy, I think there’s probably a continuum of psychological effect on health and longevity.

Elissa Epel shows us that feeling stuck in circumstances beyond our control accelerates aging of our telomeres, while meditation elongates telomeres.

I offer this in the spirit of an invitation, not an accusation: How many times have you experienced awe and wonder this week?  Why is it uncomfortable to even think about this question?  Why do we shrink from a perspective on life that may be expansively beautiful, but which interferes with our ability to play our familiar roles?

Can you be a better friend to yourself?

 

The Bottom Line

Your exercise program may be the most important factor for your mental health.

Get up and move because it interrupts your routine and encourages creativity, because it helps you feel empowered and connected.

Get your legs up in the air.  Renew the blood flow to your brain, and turn your habitual perspective on its head.

It’s reasonable to expect more from life than relief from depression and suffering.  Dare to reach for inspired joy.  Your life is an experiment.