Dr.  Harold Katcher of the University of Maryland believes that signals in our blood tell our stem cells how old to act, and that some key disabilities of old age might be reversed by serial transfusions of blood plasma from a young donor.  Plasma transfusion is a routine medical procedure, established to be safe for humans, but remarkably, its potential for rejuvenation has never been tested in humans or even in animals.

In a 2005 experiment that would make anyone with the least sensitivity to animal welfare cringe, Irina and Michael Conboy of UC Berkeley surgically joined pairs of mice so that they shared a common blood supply.  One old mouse and one young mouse became artificial Siamese twins.  For control, Conboy also paired two old mice and two young mice.

After the surgery, they injured one mouse from each pair, and monitored the healing process at a cellular level.  As expected, the young mice recovered from injury much more efficiently than old mice. The surprise was that old mice that were paired with young mice healed as if they were young.  “Importantly, the enhanced regeneration of aged muscle was due almost exclusively to the activation of resident, aged progenitor cells, not to the engraftment of circulating progenitor cells from the young partner.” In other words, it was not young cells that implanted themselves in the old mice; it was signal proteins in the blood that told the old mouse tissue to go ahead and heal as if it were young.  Something in the young blood was signaling the satellite cells of the old mice to divide and grow efficiently, as if they were young.

The Conboys went on from muscle cells to study the livers of their test animals.  The liver is constantly regenerating, and in livers of old animals this regrowth slows way down.  They found that livers of old mice exposed to young blood had rejuvenated potential for growth.

 

Some background

Satellite cells are partially-differentiated stem cells.  A pluripotent stem cell can produce daughter cells capable of taking on any role in the body – nerve, muscle, bone, blood, etc.  At the other extreme, the terminally differentiated cells of the body perform their functions but never divide to create new cells.  A satellite cell is an in between stage.  It is derived from a pluripotent stem cell, and its job is to divide and create a supply of new muscle cells only.  The Conboys found that satellite cells from older mice were rejuvenated by exposure to blood from the young mouse.  Blood is best known as white and red corpuscles, but the fluid (plasma) is important as well.  Blood plasma contains dissolved hormones, tiny quantities of powerful signal proteins.  One class of signal molecules effects notch signaling.

Notch signaling is a mechanism by which cells can respond to external signals without allowing the signal molecule to enter the cell.  It’s a lock-and-key mechanism where the key inserted from outside controls a latch inside the house.  There are four types of notch proteins, which span the cell membrane, head in the cell and tail extending outside.  The tail contains a receptor for specific signal molecules, and when one of these finds its way to the receptor, the entire molecule changes conformation along its length, reconfiguring the head which is inside the cell.  The Conboy study identified a notch signal molecule called Delta that was present in the young mouse blood, but missing in older mice.  Responding to the Delta signal, old satellite cells were reprogrammed to act young.

(In case you don’t find this to be bizarre, go back and read it again.  Old cells become dysfunctional not because there’s something wrong that can’t be repaired.  All they need is a messenger protein commanding them to Be Young!)

 

From mouse to human

The Conboys with colleague Morgan Carlson went on to explore the biology of aging stem cells in humans.  After a disappointing response to their ad seeking young volunteers to be surgically joined to genetically-matched old fogeys, they wisely decided to work instead with cell cultures.  They were able to rejuvenate old, inactive stem cells by treatment with young blood plasma.  They identified another notch signal protein that make this happen: TGF-β (“Transforming Growth Factor”).  Using TGF-β, cells drawn from a 70-year-old human were made to behave and function like cells from a 20-year-old.

 

Katcher’s Proposal

Katcher’s new paper presents a lot of background

• debunking the idea that bodies simply  wear out with age
• tracing the reasoning that led him to the conclusion that aging is a
  genetic program, a continuation of the developmental program
• citing the Conboys’ work in detail
• and continuing to present other experiments that suggest that
  senescent tissues might be capable of rejuvenation in response to
  signals in the blood.

For example, “when an aged, involuted thymus gland is placed in a young body, it is rejuvenated and regains full functionality, even though it was originally in a senescent state.” (ref)

Katcher’s paper culminates in a proposal for whole-body rejuvenation that might be practical in the near term.  Fortuitously, its safety in humans has already been established, so people might be willing to try it if a course of animal experiments shows promise.  The idea is simply to transfuse older subjects with blood plasma from a young donor, repeated often enough to sustain levels of signaling proteins that control gene expression.There is a mature medical technology for blood separation.  A fine physical filter separates cells from plasma. Red and white blood cells can be returned to the donor, with the result that the donor can safely give blood plasma up to twice weekly.  The plasma includes dissolved hormones, including notch signal proteins.

The reason this technique has been tested and developed as a medical technology is that it has been found useful for patients whose blood does not clot.  Hemophiliacs and others who are in danger of excessive bleeding routinely receive plasma transfusions, which include the clotting factors they need.  Katcher stresses that plasma transfusions have already been approved as safe for humans, so that we are ready to try the additional twist of transfusing plasma from young donors into old recipients.

 

What can we expect?

I wrote in this space last month that aging may be primarily a matter of gene expression, controlled by chemical signals.  Signals are of two kinds: intra-cellular and inter-cellular.  The former may be difficult to reprogram.  But we can intercept and replace the body’s inter-cellular signals without even a detailed understanding of what signals are necessary. Katcher’s proposal is a way to bypass many years of study, disentangling a hierarchy of chemical signals, and simply transfuse the entire complement of youthful blood factors into an older patient.

I have tentatively adopted a paradigm in which DNA methylation is the body’s aging clock, controlling gene transcription.  The choice of which genes to transcribe both governs the body’s metabolic state (including aging) and also includes signals that feed back to advance the cellular “methylation clock”.

Viewed from this perspective, Katcher’s proposal is not the holy grail of directly manipulating the methylation state of the cell. But it is a promising shortcut, addressing the inter-cellular but not intra-cellular signals that govern the “methylation clock”. We don’t know to what extent the inter-cellular signals by themselves might be able to turn back the clock, but Katcher’s proposal is exciting because it is expected to be safe and practical in the near term, and because experiments support optimism that there will like be some rejuvenation benefit.

In the most optimistic scenario, signals from the blood will change gene expression in ways that not only engender a more youthful phenotype, but also feed back again to methylation patterns, creating an even more youthful gene expression profile. In the pessimistic scenario, it will turn out that telomere attrition is far more important in humans than in mice, and that blood factors fail to produce a significant benefit because they don’t address cellular senescence.

Most speculation about anti-aging mechanisms and candidate treatment modalities is quite abstract, and cannot easily be verified.  The beauty of Katcher’s proposal is that it could be tried now in animals, and the required procedure are already approved as safe for humans.  What are we waiting for?

I’ll not be posting next week, not because it’s Easter, but because I’m moving.
See you April 7.

Deprenyl is a neuro-protective drug discovered in Hungary more than 30 years ago. It has prolonged life span in many rodent studies, and also in dogs. In the 1990s, under the brand name Selegiline(also Eldepryl and Zelapar) it became a standard treatment for Parkinson’s Disease. Parkinson’s patients who take Selegiline live longer than matched patients who take only the other standard treatment (L-Dopa). More recently the same drug (branded as Emsam) has been prescribed for depression and ADD. There is a small cult of people who take it daily for life extension, with good rationale (in my estimation). But it has an effect on mood and personality that not everyone will appreciate.

Medical literature classes deprenyl as an MAO-B inhibitor. What does that mean?

For non-specialists, the story should start with neurotransmitters. The electrical network of the brain is modulated chemically by neurotransmitters that determine how easily and strongly its signals are transduced. Dopamine, adrenaline, melatonin and serotonin are all common examples of mono-amine neurotransmitters, named for a chemical structure they have in common. Neurotransmitters are constantly being produced in response to stimuli, and broken down so their levels in the brain can be adjusted from moment to moment. The breakdown is accomplished by an enzyme called a mono-amine oxidase. There are two closely-related forms of these breakdown chemicals, known as MAO-A and and MAO-B. Type A breaks down all four of the MAO’s listed above. MAO-B specializes in dopamine.

Two important things to know about dopamine are (1) that it’s essential to the brain’s reward center that makes us feel good in response to social cues or sex or food or whatever, and (2) Parkinson’s disease is caused by death of cells in the midbrain that manufacture dopamine, so that dopamine levels are very low in Parkinson’s patients.
The last word in the description is “inhibitor”. “Mono-amine oxidase inhibitor” is a double negative – it prevents breaking down the neurotransmitters, so more of them circulates. Deprenyl in particular prevents the breakdown of dopamine.

Brain aging

All of this provides good support for understanding the function of deprenyl as a Parkinson’s drug and anti-depressant. But why should it affect aging? Why should it protect the brain? It has been known for 20 years that deprenyl protects nerve cells from toxins and even can help to rescue nerve cells after they have been damaged. Though the mechanism is not understood in detail, there are some clues. Neural growth factors have been found to increase in the brain.  Superoxide dismutase (SOD) and catalase are part of our natural protection against oxidative damage, and and both these are enhanced in the brains of people taking deprenyl. Glutathione is another of the body’s natural protections which has been found to increase (in rats) in response to deprenyl. This same study found a larger density of neurons and better retention of learning abilities in deprenyl-treated rats.

Personally, I have never taken deprenyl. In fact, I’m a purist about the quality of my consciousness – some would say obsessively so – and I stay away from caffeine, alcohol and marijuana, let alone prescription anti-depressants. But I know people who have taken Selegeline as an anti-depressant, with results that seemed to me to be noticeable from the outside. With Selegeline, they were inspired to new creative projects, full of enthusiasm, less realistic about follow-through and detail. That’s my personal observation.

And here’s a red flag: Deprenyl metabolizes to methamphetamine. Though I have no personal experience with methamphetamine, it certainly gives me pause if I were to consider deprenyl for myself, or recommend it to anyone. Why is it that deprenyl seems far less addictive and less destructive to personality than methamphetamine? It may be because typical dosages of deprenyl are small compared to recreational dosages of meth.

Life extension

The first rat study was done in 1988 by Knoll himself (discoverer of the drug), with spectacular results. Though deprenyl treatment was not begun until the rats were middle-aged, the treated rats still lived 34% longer than controls. Subsequent rodent studies continued to show significant life extension, but no one found the dramatic results claimed by Knoll.

Why the difference in results? Part of the discrepancy may have to do with dosage. High dosages of deprenyl can shorten life span, as reported by a Japanese group in 2006.

There was one study on dogs, significant because dogs live longer than mice or rats, and caloric restriction (CR) is proportionately much less effective in longer-lived animals. Does deprenyl behave like CR, with proportionately smaller effects in long-lived species? The results from this one experiment give a tantalizing suggestion: perhaps not; but the study was terminated too early to offer a quantitative estimate of life extension. The study included 33 dogs that were more than 10 years old when they were first placed on deprenyl, but the study was terminated before most of the dogs died, making it difficult to estimate the life extension benefit. 80% of the deprenyl-treated dogs survived to the end of the study, but less than 40% of the untreated dogs.

We can’t help but get the impression that deprenyl has a lot of potential as a life extension drug, and that the subject cries out for more research.  Knoll has come out quite explicitly recommending deprenyl as a generalized anti-aging tonic.  Most of the nutritional interventions that we know about that extend life span in animals work through the insulin pathway that governs the caloric restriction response. This may mean that simultaneously cutting calories while taking resveratrol and metformin has less benefit than what you might expect by adding the benefit of each of these separately. Deprenyl, however, seems to work through an independent pathway, so there is reason to hope that whatever longevity gains it offers are in addition to those from caloric restriction and CR mimetics.

Why?

We may be surprised that a stimulant can lead to longer life. What happened to “Speed kills”? Most of our intuitions about the rate of aging are based on the idea that the body is wearing out, and faster we move, the quicker we wear out. This is the “rate of living” hypothesis, which is discredited, as as I wrote a few weeks ago.  We should remember that physical activity leads to longer life span. We should think in terms of hormesis – the body’s paradoxical response to hardships and challenges. In fact, deprenyl extends life expectancy in small doses, but is toxic in higher doses – the signature of hormesis.

Is this for me?

People taking deprenyl for life extension report palpable effects on mood and energy. Meanwhile, the impact on life span is distant and largely untried in humans. If you like the way deprenyl gives you more energy, more enthusiasm, more ideas, then the thought that this drug may extend your life is a nice bonus. If you find that the drug makes you nervous and raises anxiety, if you lose sleep and are separated from your inner being, then tipping your odds for future longevity will not be worth it.

Just a few days ago, I received a missive embodying the wisdom of the East. It came from a fortune cookie at my local Chinese take-out, and its message read: “The quality, not the longevity of one’s life is what is important.”

 For basic information about healthy living for a long life, see the author’s permanent page at AgingAdvice.org.

A study this week helps to establish a relationship between resveratrol (the anti-aging tonic refined from red wine) and a family of genes known as SIRT, which seems to extend life span in some lab species by turning genes off.  But the results may be moot if resveratrol cannot be shown to extend life span in mammals, including humans.

 

Seldom do arcane questions about detailed mechanisms of gene expression make headlines in science news, but a hard-fought debate over sirtuins and resveratrol has attracted public attention since 2003. Once again this week, the debate burst onto news pages. The prospect of anti-aging drugs only partially explains the special notice; other factors are major investments in the field from Big Pharma, and some flamboyant personalities.

Science Magazine has a section labeled Perspectives where technical articles from the back of the magazine are summarized for non-specialists. But the Perspective piece on Friday was clear as mud, explaining

that natural SIRT1 substrates with a large hydrophobic residue (Trp, Tyr, or Phe) at positions +1 and +6 [such as the substrate peroxisome proliferator-activated receptor γ coactivator 1α, acetylated on lysine at position 778 (PGC-1α-K778)] or +1 [such as the substrate forkhead box protein O3a acetylated on lysine at position 290 (FOXO3a-K290)], as well as other peptides that conformed to this substrate signature, were selectively activated by several STACs.

Ever wise and patient, Len Guarente did a far better job.  In an off-the-cuff interview for the MIT news service, he explains that the crux of the question is whether compounds in the resveratrol family act through the SIRT family of genes, or whether the SIRT genes are activated indirectly as a side-effect.

This paper, I think, provides findings that are very difficult to interpret in any way other than direct activation by the [resveratrol] compounds. The strongest evidence in the paper is that they found they could change one amino acid of the [SIRT] protein, from glutamate to lysine, and that change had no effect at all on the catalytic properties of the enzyme – the enzyme still works the same way as far as you can measure, there’s no difference between the mutant and the control. However, the mutant is completely dead with regard to activation by resveratrol. They also tested some of the newer compounds – I believe it was about 100 of them – and found the same thing. The mutant enzyme was either inactive or much less active than the normal version. 

Resveratrol trials in animals

Back in 2003 when the question about the action of resveratrol and its connection to SIRT-1 first sparked a debate, it seemed crucially important because compounds in the resveratrol family seemed head-and-shoulders the best candidates for quick development as anti-aging drugs.

The benefits of resveratrol were first discovered in the early 1990s in yeast cells, where it was found to prolong life span dramatically. Next, resveratrol was tested in worms and flies, short-lived species that are easy to grow in the lab. Both these species – evolutionarily miles apart from each other as each is from yeast – responded dramatically to resveratrol. In 2006, a visionary Italian grad student made expeditions to East Africa to introduce a new lab model for aging research: a killifish that thrives in seasonal wetlands. With a life span of just four months, it is the shortest-lived known vertebrate. Once again, resveratrol performed swimmingly, extending life spans up to 80% more than 50% (at the highest dosage), and helped to launch the career of Dario Valenzano. All this pointed to an evolutionarily-conserved mechanism for modulating life span.

With life spans of 2-3 years, mice were next in line for testing. (Compared to yeast and worms, mice are practically human.)  Expectations were high, and the tests were performed by genuine enthusiasts for resveratrol, who were looking for positive results. But we were all disappointed: Life span of the mice was not increased. Puzzling, tantalizing were observations that the mice seemed healthier in so many ways.

• Inflammation and oxidative damage was down
• Arteries were healthier
• Cataracts were delayed
• Insulin sensitivity was better
• Stamina was improved

Gene expression in the resveratrol mice also seemed in some ways to mimic gene expression of younger mice, or mice on a calorie-restricted diet. Why didn’t they live longer? These results were reported with positive spin, but it was confirmed in subsequent trials: life span was extended only for that branch of the experiment working with mice that were made obese with a high-calorie diet.

Here we present a long-term evaluation of resveratrol as a CR [calorie-restriction] mimetic in mice. In agreement with a concurrent study, we show that resveratrol induces changes in the transcriptional profiles of key metabolic tissues that closely resemble those induced by CR. In liver and muscle, these changes can also be correlated to the gene expression patterns in younger animals, while in adipose tissue, the trend is reversed. Overall health was improved under all dietary conditions, as reflected by the reduction of osteoporosis, cataracts, vascular dysfunction, and declines in motor coordination; however, longevity was increased only in the context of a high-calorie diet, as reported previously… In conclusion, long-term resveratrol treatment of mice can mimic transcriptional changes induced by CR, and allow them to live healthier, more vigorous lives.  (Harvard Med study, 2008)

 

What does SIRT-1 do?

Recently, I wrote about gene regulation and aging. A different subset of genes becomes active later in life. Curiously, there is generally more gene activity at older ages. Think of this extra gene expression as haphazard and damaging to the cells’ delicate chemical poise. A smart effective anti-aging strategy would be to change the set of genes that are expressed back to a youthful profile. But there is evidence from worms and flies that the dumb strategy of cutting back gene expression across the board might also work to some extent.

SIRT-1 turns genes off in a broadly dumb way. This is done via a chemical process called histone de-acetylation. Histones are wide protein spools, around which  DNA winds to keep itself compact. Where there are acetyl groups added to the histone, the DNA winds more loosely, and is more available for expression. What SIRT-1 does is to remove acetyl groups from the histones, which has the effect of broadly dialing down gene expression.

(To turn a gene on, either subtract a methyl group from the chromosome itself or add an acetyl group to the histone.  Methylation is the other principal way that gene expression is controlled.  Methylation is directly on the chromosome itself, not on the histone, and it is both more specific and more long-lasting than de-acetylation.)

 

The search for a resveratrol-based drug product continues

David Sinclair was the most ambitious and flamboyant of Guarente’s students. He went on to run his own lab at Harvard Med School, and to found a for-profit company called Sirtris, whose mission was to explore engineered variations on the theme of resveratrol. In 2008, Sirtris was bought by Glaxo SmithKline for an eye-popping $720 million, leading to widespread speculation that Sirtris had developed a promising candidate age-retarding drug. But in 2011, Glaxo announced that it was discontinuing trials of all the Sirtris drug candidates.

A recent short-term study of resveratrol in middle-aged women found none of the metabolic benefits reported for animals. These researchers from Washington University reported that resveratrol failed even to raise levels of sirtuins. Still, human trials are continuing for a handful of the hundreds of sirtuin-activators that Sirtris has identified. Science journalist David Stipp has written about positive results in humans and mice

And if I were an obese mammal with hypertension, I’d be sorely tempted at this point to try taking modest daily doses of a resveratrol supplement for a month to see whether it brings down my blood pressure. While I wouldn’t expect such an experiment to make me live a lot longer, I think I could justifiably entertain the hope that it just might help me age more gracefully.

 

 

The thymus is a thumb-sized organ just above the sternum where our immune cells are trained to recognize self from other. It is fully developed by the time we are 10 years old, but after that it begins gradually to shrink. By age 25, it has already lost 30% of its mass, and by age 60 it is less than half its peak size. There is evidence that this is related to the immune decline that contributes so much to growing mortality risk with age, and that reversing that decline might lead to longer, healthier lives.

 

As we get older, the white blood cells that protect our bodies from cancer and infection become less effective. They make two kinds of mistakes, for which statisticians apply the creative terminology “Type 1” and “Type 2”. Type 1 mistakes are a failure to recognize the invader, and it is the reason that, for example, older people frequently die of influenza and pneumonia, while younger people seldom do. Type 2 mistakes are false positives – inadvertently attacking the body’s good, healthy cells as if they were an invader, with consequences that are even worse for us than Type 1. It is the root cause of auto-immune diseases and inflammation that are hallmarks of old age in mammals.  Decline of the thymus is intimately related to both types of errors.  There is indirect evidence that thymic involution exacerbates other aspects of aging as well, and there is lots of evidence correlating immune decline with mortality, independent of age.

T-cells are a kind of white blood cell that responds to new infections, and then remembers for many years (“memory T-cells”) the disease to which you were exposed, so that if it ever appears again, your immune response is jump-started. The “T” in “T-cell” stands for thymus, and it is in the thymus that these cells are trained to recognize all the 30,000 or so proteins that the body produces internally, and to attack any protein that’s not on its “white list”.

Once an invader is recognized and an immune attack is mounted, the particular cell that successfully identified the invader is rewarded with profuse replication, flooding the bloodstream with copies of itself until the infection is successfully repelled. After that, most of the clones die away, but a few remain circulating in the blood for many years afterward, just in case the same pathogen should appear in the future.

T-cells, then, are either “naive” or “memory” cells. It is the naïve cells – newly manufactured and trained in the thymus – that enable you to launch a defense against new (to you) diseases. The number of naïve cells declines with age, and the decline has been linked directly to shrinking of the thymus gland

Thirty years ago, a research lab in Tokyo tried grafting thymus glands from young mice into old mice. They repeated the operation every few months throughout the the lives of the older mice, and the mice lived half again as long as controls that didn’t receive transplants, despite the periodic trauma of the surgeries. (Of course, the donor mice had to be genetically very close to the host mice, because the immune system is ultra-specific to individual genotype; but that was easy to arrange, because lines of laboratory mice are routinely inbred so that they are genetically homogeneous.) Thymic involution is common to all vertebrates, and it is a good bet that it contributes substantially to aging in most if not all species, including humans.

There is no known benefit to humans or any animal from having a smaller thymus, so thymic involution is a good candidate for a mechanism of programmed aging, an aging clock like those described in this space two weeks ago.

 

What to Do About It

There are many studies with humans and animals reporting that thymic involution can be reversed and immune function restored with growth hormone (GH).  I hasten to add that I don’t recommend growth hormone for other reasons: it can lead to diabetes and cancer. Growth hormone has also been associated with increased mortality when administered to critically ill patients, (even though they were deficient in GH). A friend and colleague of mine experimented on himself in a controlled, medically-supervised trial, and succeeded within one month in regrowing his thymus and increasing immune function, – after which he was wise and knowledgeable enough to discontinue his own treatment (written up here).

Besides GH and thymus transplants, other interventions have measurable but less dramatic benefit for regrowing the thymus. These include thyroxine, interleukin-7 (IL-7) and luteinizing hormone (LH), supplementation with melatonin, arginine or zinc, and castration. (ref).  I realize that some of these interventions may be more appealing than others.

The hormone ghrelin has also been found to stimulate thymus growth in mice. The mechanism seems to be related to GH, since ghrelin binds to a class of receptors called Growth Hormone Secretagogues, stimulating endemic production of GH. Ghrelin also make you hungry, and there was some hope a few years back of manipulating ghrelin levels as a diet aid. This is one more suggestion that the same signals that make the body hungry contribute to life extension from calorie restriction (ref).

Thyroxine actually has other anti-aging properties as well – a topic for another day. LH may be a mild alternative on the castration axis: it tends to suppress production of testosterone. Leuprorelin (trade name “Lupron”) has been prescribed to prostate cancer patients because it cuts off testosterone very effectively, and presumably for that reason it would be a non-surgical substitute for castration.

IL-7 has been studied as therapy for cancer and some other illnesses where increasing immune response is desirable . In mice as in people, IL-7 has been shown to increase T-cell production and to stimulate re-growth of the thymus. Is it safe to use for a general population, not in extremis? The reason we’re not likely to find out soon is that IL-7 is priced like a cancer drug, at $10 million per gram

 

Neglected Opportunities

Research on reversal of thymic regrowth is a backwater of medical science. If this is an opportunity for major gains in life expectancy, then it is a neglected opportunity that has attracted little interest or funding. Based on evolutionary arguments, the general attitude seems to be that if the thymus shrinks over a lifetime, then it must not be much needed; or, conversely, that a Law of Nature assures us that any therapy to maintain its function must necessarily have dangerous side-effects that outweigh the benefits. Wikipedia calls it an “evolutionary mystery”:

Since it is not induced by senescence, many scientists have hypothesized that there may have been evolutionary pressures for the organ to involute…the best time to have a prodigiously functional thymus is prior to birth. In turn, it is well known from Williams’.theory of the evolution of senescence that strong selection for enhanced early function readily accommodates, through antagonistic pleiotropy, deleterious later occurring effects, thus potentially accounting for the especially early demise of the thymus.    (Wikipedia)

But this is ideology, a misplaced faith in general theory over explicit experimental results. Reality in the lab appears to be that

Thymic involution, adrenal involution, and somatic involution seem to provide no obvious benefits in humans that would outweigh the benefits of their elimination once the hazards associated with such issues as insulin-like signaling can be set aside. Fortunately, methods of eliminating or at least blunting thymic, adrenal, and somatic involution or their effects are already known…and will surely be improved in the future. (Fahy, 2010)

I remain hopeful that

An understandin of the causal mechanism of thymic involution could lead to the design of a rational therapy to reverse the loss of thymic tissue, renew thymic function, increase thymic output, and potentially improve immune function in aged individuals. (Aspinall and Andrew, 2000)

 

Much of the material in this article was derived and elaborated from a book chapter by Greg Fahy, who also edited the volume The Future of Aging.  Chapter 15 by Richard Aspinall and Wayne Mitchell in the same book offers more details.