Michael Fossel Michael is President of Telocyte

November 22, 2013

Extending Life, Not Misery

Filed under: Uncategorized — admin @ 6:37 pm

Extending Life, Not Misery

Michael.fossel@gmail.com

 

Most of us assume that aging equals illness.

To be honest about it, we don’t usually put it that bluntly and we often deny it, even to ourselves, and yet we tend to assume that unless we are struck down suddenly – an unexpected automobile accident, a sudden pneumonia, a fatal heart attack – we will gradually lose the ability to care for ourselves, lose the ability to live in our own homes, and lose the ability to enjoy our lives. Are we wrong?

What if we could cure age-related disease?

What if we could be older, true, but be as healthy as the average young adult? The assumption – aging equals illness – shows itself in how we respond to the question “Do you want to live to be 120?” Most of us don’t. The Pew Foundation, and then the Canadian Association of Retired Persons, asked this exact question. The majority of us said we wouldn’t want to live that long, even if people had access to “medical treatments that slow the aging process and allow them to live decades longer”.

But look carefully at what the question implies.

Most of us – having close friends and relatives with Alzheimer’s disease or who live in a nursing home – immediately translate the question from “do you want to live to be 120” into “would you be willing to live in a nursing home, unable to care for yourself, for another 30-40 years?” We make this translation unconsciously, but quite naturally: after all, that’s what it means to be that old, doesn’t it? When look at the question with this assumption in our minds, why would we want to live to be 120? Not surprisingly, most of us wouldn’t. Why would you – or anyone – want to be kept alive even longer, unable to feed yourself, unable to recognize your own children, and unable to enjoy life around you? Not surprisingly, most of us would prefer an easier fate, a sudden illness for example, rather than submitting to decades of nursing care.

But let’s change our question a bit.

Instead of “do you want to live to be 120 (in a nursing home)?”, let’s ask about a different outcome. Imagine that we could prevent Alzheimer’s disease, prevent heart disease, prevent osteoarthritis and all the “…the thousand natural shocks that flesh is heir to”. Imagine that you could have the health and function of a 30 or 40 year old. What if we could “turn back the clock” and prevent age-related disease? If you could have the health of a much younger person – even at 120 – what would you do then? Look at the question now, with different assumptions. The question becomes more interesting: “Do you want to live to be 120 if you could have the health of a young person?” It’s such an odd, such an unbelievable (beyond the pale?) question that most of us discount it immediately, and yet…

And yet perhaps it’s not so odd a question after all. As it turns out, a great deal of research shows that we may soon do exactly that. We can now reverse aging in human cells and in human tissues in the laboratory and at least one Canadian biotech firm is about to take the same approach in curing age-related diseases. They may well change everything you think you know about aging and disease. Older yes, but why not healthier as well?

The original question assumed a tragic end. At a very real level, the Pew Foundation was asking us if we wanted to be unhealthy for a longer time. A better question is whether or not we want to be healthy for a long time. It’s a much better question, particularly in light of what is about to happen to our ability to cure age-related disease.

Or try an even better version of the question. 

If you had only two choices, would you rather suddenly become 30 years old or suddenly become 90 years old? Would you like to have the health of the average 30 year-old  or would you want the health (and the health problems) of the average 90 year-old? What if you could live to be 120,  not by living longer in a nursing home, but by being healthy, living in your own home, and being free to enjoy an active life? But is this realistic?

It is if we can cure age-related disease, and we may soon do precisely that.

Some of us discount the question for other reasons, feeling it would be wrong to “grasp after youth”, yet we chose health every day, with nary a pause for thought. We even chose the mere appearance of health, even when it does nothing to improve our health. It’s not surprising that we should take antibiotics for pneumonia and replace our aging knee joints when osteoarthritis prevents our walking without pain, but we also dye our hair and pay a truly astonishing amount for Botox, when neither of these provides anything but an illusion.

Soon, however, we will be able to prevent and cure Alzheimer’s disease and regrow our own natural knee joints, so that they work as well as they did when we were young adults Would you want to play tennis at age 90 if your knees and your heart were healthy?

Until now, when it came to aging, the medical community has also tended to “answer the wrong question”. We still think of aging as inevitable and age-related disease as incurable. But the outcome is that we often discount disease in our elderly patients, treating them often as not only incurable, but invisible. Few of us would be callous enough to ignore the suffering of children, yet some of us have quietly ignored suffering in the elderly, perhaps not because we don’t care, but because we feel impotent in the face what we thought of as inevitable disease.

Research now shows that this view is naïve. Aging is not inevitable nor is age-related disease incurable. We need to take the results we have in cells and animal studies and go further: we need to eradicate the diseases of aging. Suffering is not inevitable, nor can we afford to ignore the elderly. Over the past century, we worked hard – and worked together – to cure polio and other common diseases of the young. Compassion for the young is common; an equal compassion for the old should be no less equally common. It is time to find out what compassion and hard work can accomplish.

It is time to save both our health and our lives.

November 12, 2013

Telomeres and Cancer

Filed under: Uncategorized — admin @ 4:09 pm

Telomerase and Cancer

Michael.fossel@gmail.com

 

 

Telomerase does not cause cancer.

The statement is accurate, but it’s not that simple nor is it a naïve concern.

Telomerase and cancer are clearly linked – telomerase has been called “the two-edged sword” with aging being one edge and cancer the other – and the question thus deserves a more complete and more sophisticated answer. As always, discussions that involve causation tend to miss the point, resulting in misconceptions and errors. Instead of asking about causation, consider a few questions that are far more practical and clinically useful:

          If we increase telomerase in somatic cells, would the incidence of cancer rise in an average group of healthy patients?

          If a patient already has cancer and we increase telomerase in their somatic cells, would that patient get better or worse?

          If we have a population of healthy patients and we wish to decrease the overall incidence of cancer, would it be better to increase or decrease telomerase activity?

These sort of questions are much closer to the nub of what we actually want to know, as they constitute useful clinical information, information that is useful to both the physician and the average patient. Putting it bluntly, if I want to be healthy, do I want telomerase or not? To answer just as bluntly, you generally want more telomerase rather than less, or to put it more accurately, you generally want longer telomeres rather than shorter telomeres.

The reason the answer is “generally” true is that elongating your telomeres – like almost every function in biology and every therapy in medicine – has both an upside and a downside. The upside is that longer telomeres stabilize your genome, and hence lower the probability of cancer. The downside is that – once you have a cancerous cell – cancer needs to maintain telomeres just to survive. In other words, long telomeres prevent cancer, but cancers require telomeres or they may spontaneously go into remission.

There is a balance of risk. If you don’t have cancer, you definitely want long telomeres. If you already have cancer, you would prefer it if the telomeres in your cancer cells would continue shortening and kill the cancer cell before the cancer cell kills the rest of you.

Consider why this balance occurs. In normal cells, the repair and recycling of cellular elements – in this case we can focus on DNA repair – depend on changes in telomere length: as telomeres shorten, DNA repair slows down. In the young cell, DNA maintenance is stunningly accurate and efficient. In the aging cell, DNA maintenance has become slipshod, showing decreasing accuracy and efficiency. In old cells, the genome is no longer defended as competently and the outcome is an increasing number of mutations and errors, leading to cancer. To put it simply, the longer your telomeres, the more stable your genome. As telomeres shorten, genomic stability falls and cancer incidence rises.

On the other hand, once a cell’s genome has accrued enough errors to become cancerous, there are still three internal cellular obstacles: DNA repair, the cell-cycle braking system, and telomere loss. If DNA repair fails (which occurs as the telomere shortens), then cell division is generally halted as the cell detects DNA errors. However, as the telomere shortens, the cell also becomes sloppier in applying the “brakes”: the aging cell is more prone to continue dividing even in the face of DNA damage that would halt a younger cell. This leaves the telomere as a final defense. In normal aging cells, shortened telomeres result in a failure to divide (or to put it more accurately: a slower rate of division, a decreased likelihood of continued division, and an increased likelihood of apoptosis or even necrosis). If the cancer cell no longer divides, then it isn’t a clinical problem. If it can’t grow, it can’t kill you. Unfortunately, there are a number of ways that cancer cells elude the problem of telomere loss, at least for a while, and almost all of them involve maintaining telomere length. Not surprisingly, telomerase is expressed in about 85% of human cancers and telomerase inhibitors are seen as potential cancer therapies. If we have cancer cells, then we would prefer it if their telomeres would be entirely lost, resulting in dead cancer cells. If you already have cancer and we re-extend your telomeres, that wouldn’t cause cancer, but it might increase the ability of your cancer to survive and metastasize.

In short, telomere extension might increase mortality in patients with a pre-existing cancer, but if patients don’t already have cancer, then telomere extension would prevent cancer from occurring in the first place. Neither telomerase nor long telomeres cause cancer, but either telomerase or long telomeres could permit cancer to grow once it gets a foothold.

To return to our practical questions, let’s construct some evidence-based, rational clinical advice for a hypothetical patient population. If a patient comes to us with a known prostate cancer, we would probably recommend against a telomerase therapy. This recommendation is not because telomerase causes cancer, but because telomerase therapy might increase the likelihood that the cancer would continue to grow and would metastasize. On the other hand, if a patient comes to us with no known cancer, we would recommend telomerase therapy to prevent getting cancer in the first place.

This is not a new therapeutic dilemma: it’s actually true of a great many other clinical options. Consider exercise: does it cause heart attacks or is exercise good for you? Most of us – both physicians and the general public – are in favor of exercise as a preventative action: patients who exercise are considered to be less likely to get a heart attack, for example. On the other hand, if a patient has just had a heart attack this morning, we certainly don’t recommend that they run a marathon this afternoon. Does exercise “cause” heart attacks or does it prevent heart attacks? Exercise doesn’t actually cause heart attacks, but it can contribute to them or trigger them if you already have enough atherosclerotic disease. Most of us, however, think of exercise as healthy, and with good reason.

Overall, telomerase therapy is – like exercise and with similar caveats – a beneficial clinical intervention, but one that must be discussed in context.

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