When and How Does the Decay of Your Immune System Start?
Permalink | View Comments (19) | Post Comment | | Posted by Reason

Evolution is a harsh but efficient mistress; you can consider yourself surprisingly well optimised as a piece of machinery, but your warranty only goes so far as the number of years in which your recent ancestors contributed to the success of their offspring. After that, you're on your own - biochemical processes unwind and break down free from any past selective pressure to do better.

Take the immune system, for example, one of many absolutely vital components in the very complex system that supports your life. It is remarkably well optimized for reliable and effective use of resources in early and mid-life, but the rules that govern that optimization lead to a system that breaks down badly after extended usage. A crude illustration of the problem in the adaptive component of the immune system is much as follows:

  • Your immune system is capped in its use of resources; it can only have a set number of T cells in operation at one time.

  • A reserve of naive T cells is needed to effectively respond to new threats. These are untrained cells that will be educated and drafted to combat new intrusions.

  • A small reserve of memory cells is needed to respond effectively to previously encountered threats - one reserve per threat.

  • The more threats you have encountered, the more cells become devoted to memory; eventually you don't have enough naive T cells left to mount any sort of effective defense.

The story is more complex than that, but this appears to be the essential problem of design at the core of the aging immune system - you simply run out of space. Given the large degree to which immune system decay contributes to age-related frailty, suffering and death, it would be a big step forward to find a way to repair this mode of failure.

In recent years, it has become clear that this running out of space is not caused by a wide range of immunological threats - rather one type of virus is largely responsible for the entire problem.

Why Our Immune System Degenerates:

Throughout our lives, we have a very diverse population of T cells in our bodies. However, late in life this T cell population becomes less diverse ... [one type of cell] can grow to become more than 80 percent of the total [T-cell] population. The accumulation of this one type of cell takes away valuable space from other cells, resulting in an immune system that is less diverse and thus less capable in effectively locating and eliminating pathogens.

Decline of the Aging Immune System:

Longitudinal studies are defining progressive alterations to the immune system associated with increased mortality in the very elderly. Many of these changes are exacerbated by or even caused by chronic T cell stimulation by persistent antigen ... Lifelong exposure to chronic antigenic load is the major driving force of immunosenescence, impacting on human lifespan by reducing the number of naive antigen-non-experienced T cells, and, simultaneously, filling the immunological space [with] antigen-experienced T cells. Gradually, the T-cell population shifts to a lower ratio of [non-experienced] cells ... the repertoire of cells available to respond to antigenic challenge from previously unencountered pathogens is shrinking.

Inflammaging:

Our immune system has evolved to very efficiently get rid of acute infections in young bodies but it has not been selected to get rid of subclinical viral infections in old age. ... The constant attempt to suppress slow-acting viruses such as cytomegalovirus (CMV) could eventually throw the immune system out of balance ... CMV is a passive infection in many old people - and more and more of the immune system is devoted to fighting it.

Destroying Chronic Infection:

One main reason your immune system fails with age appears to be that chronic infections by the likes of cytomegalovirus (CMV) cause too many of your immune cells to be - uselessly - specialized. ... researchers are looking into a possible way of clearing these infections from the body.

CMV doesn't really hurt you at all in the short term; most people don't even show symptoms. But because you cannot clear it from your system, its presence chews up more and more of your limited immune resources with time. When does this process get underway, and when does it cross the line? A recent paper from the open access journal Immunity & Aging looks at setting some boundaries to that question:

We observed consistently high frequency and phenotypically mature (CD27 low, CD28 low, CD45RA+) CMV-specific CD8+ T cell responses in children, including those studied in the first year of life. These CD8+ T cells retained functionality across all age groups, and showed evidence of memory inflation only in later adult life.

...

CMV consistently elicits a very strong CD8+ T cell response in infants and large pools of CMV specific CD8+ T cells are maintained throughout childhood. The presence of CMV may considerably mould the CD8+ T cell compartment over time, but the relative frequencies of CMV-specific cells do not show the evidence of a population-level increase during childhood and adulthood. This contrast with the marked expansion (inflation) of such CD8+ T cells in older adults.

These results suggest that the accumulation of CMV-specific T cells is not a gradual process throughout life, but rather a more exponential process, or a transition from slow to fast accumulation later in life. There may be a therapy lurking in a greater understanding of how that transition comes to pass.

I should not close thoughts on the matter of age-related decay of the immune system without looking at a SENS-like approach to the problem: something direct and from the engineering school, based upon what we already know and using the tools available to us now or in the near future. The problem is that we have too many of a certain type of cell; the tool would be one of the new technologies enabling precision targeting of cells by their unique surface biochemistry - perhaps a dendrimer therapy with the right attachments. What we'd want to do is eliminate all those memory T-cells specific to CMV that are clogging up the system. This is very similar to the problem faced by cancer researchers; you need to nail all the bad cells, but you can't risk harming other cells or putting undo undue stress on the patient's system. Large amounts of time and money are going into solving this problem today, so we can expect to see a brace of suitable technologies to be adapted to this sort of use in the years ahead.

Will this sort of approach work? There is precedent for attacking, suppressing, manipulating or destroying components of the immune system when they malfunction or otherwise get in the way; destroying CMV-specific memory cells is somewhat less drastic than some immune therapies attempted in the past or under development today. After all, you would be removing cells that appear to be largely useless. I think it's well worth exploring.

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Comments

Is apoptosis relevant and, if so, what role might it play?

Posted by: DRJ at December 11, 2006 4:16 PM

"putting undo stress"

So undoing the problem creates stress?

Posted by: G Hanson at December 11, 2006 8:09 PM

Typo - should be "undue."

Posted by: Reason at December 11, 2006 9:33 PM

DRJ - I will cheerfully admit to ignorance on that question. I'm don't know how changes in the cellular life cycle (and especially its end states) impact the effectiveness of the immune system as a whole.

Posted by: Reason at December 11, 2006 9:47 PM

How would apoptosis be relevant? Do you mean, apoptosis of crowding T-cells that are adapted to versions of cytomegalovirus that have gone extinct? That's one source of confusion, we're always adapting to new forms, but are the old forms still there, or not?

Posted by: Jordan at December 12, 2006 10:19 AM

The real problem with immunosenesence is the chronicity of specific pathegens and how that effects the Th1 vs TH2 ratio. IL10 down regulates the TH1 response thereby skewing the immune response towards TH2 which causes imflamatation and reduces responses against cancer, virus ect. It may well be prefered to to skew the immune response leaning TH1 which will increase NK cells IFN and other anti microbial cell mediated responses.

Posted by: Patrick ONeill at February 1, 2007 7:55 AM

At what age do we have the best immune system?

Posted by: Treasa at February 27, 2008 9:33 AM

do you think that a general diagnosis/treatment campaign would make populations live longer?

on the wikipedia entry (https://en.wikipedia.org/wiki/Cytomegalovirus) i see that most but not all people are infected, that it can be diagnosed, and treated.

could it be tried in mice first?

Posted by: AgeVivo at December 27, 2008 12:52 PM

Shouldn't we also be considering the effects of antibiotic overuse when exploring longevity of the Immune System?

Posted by: Wendy Carrington at April 4, 2009 11:51 AM

When does a human's immune system slow down?

Posted by: lardhead johnson at April 8, 2009 8:56 AM

What about immunizations. Specifically the flu vaccination. Over one's life span wouldn't it deplete/saturate a lot of T cells memory. So the question is, should one get a Flu shot every year if they are normally never sick and are healthy. Of course virulent, highly lethal strains excepted.

Posted by: Ted Gray at June 20, 2009 8:12 AM

Much recent focus is on the age-dependent decline of hematopoietic stem cells and their repopulating capacities. And yes, apoptosis, necrosis, and quiescence processes appear to be important.

Posted by: georgeloy at April 20, 2011 4:20 AM

By early adulthood, something like 50% of people in developed Western countries have cytomegalovirus(CMV.) By the time they reach old age something like 90% of people in developed Western countries have CMV. There is a gradual increase in CMV prevalence with age.

As briefly outlined in the article, infection with CMV(and the chronic inflammation it can lead to) may play a significant part in many of the common diseases and decline associated with aging.

CMV is spread by bodily fluids like saliva between people(do some research on the web to find out infection risks.) However, with well-chosen increased hygienic practices, your chances of being one of the 10% that reaches old age without being infected by CMV may increase significantly.

If anyone is interested, in this let me know. I'm intending to expand on this issue, and describe my practices and and further details at some point on one or more of the large life-extensionist forums.

Posted by: Smarty at June 10, 2011 11:00 PM

Other cells of the immune system are also directly affected by aging. The activity of leukocytes,(white blood cells. B cells, T cells, monocytes, macrophages, basophils, eosinophils, neutrophils, and natural killer cells) are also reduced in the elderly, although there is very little data available on the effects of aging on these cell types.

Posted by: Ken @ Natural Herbal Remedies at June 15, 2011 9:39 AM

If a detective budget was cut in his pursuit to find violaters
than he will not arrest many of them because he doesn't have
the tool proper nor resources to do so.

With that said...

If we choose not to consider that if our body are expose to over
75,000 chemical (Directly or Indirectly)just to be conservative and
they are some how recorded, than why would it later in life just fail.
when cells are replenishing themselves everyday.


Several thing happen over time.

The body builds more outside chemical volume. We are
constantly surround by chemical throughout our living quarters and
do receive some exposer to them.I have read disturbing reports that
individuals have chemical throughtout there bodies, unknowingly.

It almost suggest a direct link, what do you think?

On the other hand we now know that a LACK of vitamines D causes rickets.

Posted by: Diamond at December 8, 2011 11:29 PM

How can anyone increase "T" cells and their resistance to all diseases??????

Posted by: Celle Gerber at June 7, 2012 12:34 PM

Adaptive Evolution:
[The adjustment of an organism to its environment, or the process by which it enhances such fitness]

“In the on-going process of human species evolution, human body slowly adapts to its environment─ like quality of air, water, food, radiation levels, stress, trauma and the physiological impact of its social networks. It’s perhaps only during the initial transition phase that adaptive change is not recognized, and therefore, is dealt with as a foreign object initiating a cancerous reaction. Eventually, however, the DNA is ever so gradually altered that we continuously become mutants of ourselves. Think about it! Ten thousand years from now, we won’t look anything like what we look like today… but our mutants will be healthy in their own way─ after having adapted to their environment and with altered DNA.”

… Quote by Anant Goel

Posted by: Anant Goel at December 4, 2012 11:15 AM

Re: Adaptive Evolution

Considering the rate at which chemicals are produced in our environment is several thousand fold the mutation rate - the rate of biochemical intoxication is much faster than we are evolutionarily equipped to process. To think we can biochemically out-run the rate of chemical damage to our bodies via adaptation is mathematically highly improbable.

Furthermore, the toxic burden of each generation is greater from pre-conception onward. Each subsequent generation is conceived and born in a greater "toxic burden" intracellularly and enters a more chemically burdened environment after birth than the previous generation - remember we live in a sea of persistent environmental pollutants which do not biodegrade at the same rate they are produced and hence, bio-accumulate and bio-amplify in living systems.

From genetics we know most mutations are maladaptive. A small percent of mutations are adaptive but we are increasingly at odds with the rate on contamination in the environment with lethal substances such as radiation or chemical pollutants which wreak metabolic havoc at earlier life stages - leading to an earlier onset of chronic and degenerative diseases including infertility in men and women - further decreasing the chance of adaptive evolution.

Posted by: Dr. Green at December 9, 2013 9:36 AM

Extrapolate from limited data that your adaptive immunity decline is nearly impossible to overcome and sure enough, it will be.

I offer a different solution: Make the CVM irrelevant.

You glanced over the production of T-Cells in the Thymus gland. We know that infants who are more readily breastfed have much larger (on the order of 20x) the thymus size as their lesser-fed peers.

So what's in mother's milk that does this? Any applications there?

Second, the thymus involutes partially in response to oxidative stress, partially in response to hormonal changes onsetting with puberty. As the thymus involutes blood markers of its function tend to go with it. Funny thing is, in mice and pig models L-arginine fortfied food stock improves blood markers of thymus function. Google Scholar or PubMed search it.

I'm not sure I buy into the capped T-Cell notion. The Wikipedia article, for whats its worth, states very plainly that T-cells are spawned from stem cells in bone morrow, make their way to the thymus, and then grow to what we call T-cells or are terminated because they auto-react to the body. Assuming the authors of this article aren't making this up, that means you want to think about stem cells and bone marrow for the adaptive immune system, in addition to breast milk and L-arginine to improve its function. Research-wise of course. I'm not recommending you drink breast milk (ick!).

Posted by: EM at February 18, 2014 5:08 PM
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