What is Aging? Most Scientists Still Get it Wrong

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Funding Aging Research

What is Aging? Most Scientists Still Get it Wrong

Dear Future Centenarian,

Dr. Josh Mitteldorf is an astrophysicist who has devoted a major part of his life studying aging and what to do about it. He writes extensively for h+ Magazine, and this article is so good that I wanted to share it with you:

Most people misunderstand what aging is.  It™s not just the public who have been deceived ” Most scientists and medical researchers who study aging are on the wrong track.

The culprit is the natural medicine movement that has dominated thinking about our bodies for the last 50 years. Respect the body™s wisdom. Work with the body to fix what has gone wrong. This approach has worked so well with injuries and many diseases that it is understandable that people want to extend it to aging as well.

Diseases of aging have been treated as if they were something that goes wrong, something we have to help the body to fix. But in fact, the evidence accumulating in recent decades is that aging is not something that goes wrong, and the body is not trying to fix it.  Aging is natural. It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction.

How do we know that aging is an active process of self-destruction, and not just the body wearing out?  There are a number of indications, becoming clearer all the time.

For one thing, if the body were trying its best to keep in good shape, but can™t help wearing out over time, we would expect that damage to the body makes aging happen faster. On the contrary, most kinds of external damage actually make us live longer. The best example is exercise, which generates free radicals like crazy, tears muscles and puts little cracks in our bones.

And yet, people who exercise tend to be healthier and live longer than others who don™t. Starvation is also a way to live longer. Animals in the lab that are kept on very low calorie diets live much longer than those that have enough to eat.This is a clear indication that the bodies that get plenty to eat aren™t really trying to live a long time.

If the body were doing its best to forestall aging, but succumbing eventually to wear-and-tear, we would expect that as we get older the repair functions would be going full-tilt.  But in fact, all our repair and protection systems gradually shut down as we age.  Stem cells, which produce new body tissues, gradually stop working.  And the anti-oxidants that protect us from chemical damage are dialed down in old age, so we don™t have enough of such enzymes as CoQ10, SOD and glutathione.

Clearest of all: there are actually self-destruction mechanisms that we can see in action.  One of them is inflammation. When we are young, inflammation protects us from invading microbes, and kills diseased cells; but when we get old, inflammation is dialed up much too high; it kills healthy cells, inflames our arties, leading to heart disease, and inflammation causes cancer as well.

Another mechanism we can see in action is called apoptosis, or cell suicide.  When we are young, only cells that are diseased or defective remove themselves via apoptosis; but when we are old, healthy muscle and nerve cells simply fall on their swords and die, leading to weakness of muscle, weakness of mind and Parkinson™s disease.

This explains why natural medicine has been so helpful for infectious diseases, immune function and response to trauma, but in stark contrast natural medicine has failed to make headway against cancer and Alzheimer™s disease, and has made only marginal progress against heart disease and stroke.

For these diseases of old age, we need to abandon the natural approach, and instead simply trick the body into thinking that it is younger. Then it won™t try to shut itself down.

In fact there are some intriguing indications that this might work. There are researchers working with this approach and they have produced some dramatic successes just in the last few years:

Every chromosome in every cell contains a time-keeper, tacked onto the tail end of the DNA. This is the telomere.Simply by resetting the telomere clock, scientists have produced dramatic results in lab animals, reversing aging and making animals younger.

When the telomere clock signals a critical age, the cell becomes senescent.  It goes and strike and refuses to do its job. Worse yet, it sends signals to nearby cells that cause the other cells to become inflamed and cancerous.  Recently, scientists have had remarkable success making mice live longer simply by removing the small number of senescent cells.

As we get older, the hormones circulating in our blood gradually change.  This is the principal way that the body knows how old it is.  There are youth hormones that promote rebuilding and high-efficiency energy output; and there are old-age hormones that turn up inflammation and cell suicide and signal the body to gradually destroy itself.  Scientists have begun to have success by increasing the former and decreasing the latter, resetting the hormone profile of an old animal to match that of a young animal.

These approaches have not yet made front page news, but scientists in the field already recognize their dramatic promise.  If all goes well, we should expect breakthrough treatments that extend life and prevent the debilitating diseases of old age, coming on-line in the next few years.

Author™s Disclaimer: This is my own perspective, shared by a handful of world-class aging scientists, but it is not yet mainstream.  In addition to the two views described here“programmed aging and wear-and-tear theories“there is another class of theories favored by mainstream evolutionary scientists, based on compromises that evolution has been forced to make. These compromises have been made up ad hoc to avoid the inference that aging evolved to benefit the community, not the individual.

There are a great deal of genetic phenomena, as well as hormesis, that can only be explained by programmed theories.

More Life,
David Kekich

P.S. If you™re a reader, you may enjoy this. Zoltan Istvan wrote a disruptive, controversial and action-packed novel with open-ended lifespans as one of its core themes. The Transhumanist Wager is available as a free Kindle download for a limited time at Amazon. 

Here's the link: http://www.amazon.com/s/ref=nb_sb_noss?url=search-alias%3Daps&field-keywords=The+Transhumanist+wager
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Latest Headlines from Fight Aging!

Transferring Calorie Restriction Benefits - Monday, January 19, 2015
Factors in the blood that affect the behavior of tissues in beneficial ways are a popular topic in aging research at the moment.

Researchers are beginning to identify proteins whose amount in circulation changes in reaction to rising levels of damage in aging, and which if altered in old animals can partially reverse some aspects of age-related decline in tissue function. Aging is one set of changes, but what about other differences between individuals such as the beneficial changes to the operation of metabolism brought on by calorie restriction?

Researchers would very much like to recreate calorie restriction benefits without the need to eat less, and as a result of findings elsewhere the approach of altering levels of various factors in the blood is now getting a second look. The example quoted here is a study in cell cultures only, but is still somewhat interesting.

Read More https://www.fightaging.org/archives/2015/01/transferring-calorie-restriction-benefits.php

A Focus on Regulatory Systems in Aging - Monday, January 19, 2015
Much of modern aging research, too much in my view, focuses on regulation of aging and the prospects for changing regulatory processes to modestly slow the progression of age-related frailty and disease.

Aging is caused by the accumulation of a few types of cellular and molecular damage and so these regulatory processes and their changes in aging are largely reactions to that damage.

They are the wrong place to be intervening for best effect, and the focus should instead be on repair of the root cause damage. That remains a minority view at this time, unfortunately, which is why it is so important to raise enough funding to produce definitive proof of its greater effectiveness as a basis for therapies.

This paper is more indicative of how a majority of researchers think about the situation, however. This view explains why those interested in enhancing longevity are most often found working on expensive, marginal ways to alter the very complex reaction to damage rather than addressing the damage itself.

Read More https://www.fightaging.org/archives/2015/01/a-focus-on-regulatory-systems-in-aging.php

Heart Rate Reduction and Longevity in Mice - Tuesday, January 20, 2015
These results suggest that a modest reduction in heart rate leads to a modest increase in life span. The researchers here at least monitored body weight, as I would otherwise immediately suspect inadvertent calorie restriction as a more likely cause of life extension than the proposed mechanisms related to heart rate.

Read More https://www.fightaging.org/archives/2015/01/heart-rate-reduction-and-longevity-in-mice.php

More Data on the Effects of Sitting on Mortality, Independent of Exercise - Tuesday, January 20, 2015
In recent years the data gathered from large epidemiological studies have suggested that more time spent sitting correlates with higher mortality independently of the level of exercise undertaken by an individual. This association seems fairly robust as it has been replicated in a number of different data sets and by different research groups. Here is a survey of these results.

Read More https://www.fightaging.org/archives/2015/01/more-data-on-the-effects-of-sitting-on-mortality-independent-of-exercise.php

Aneuploidy and Aging - Wednesday, January 21, 2015
Aneuploidy is the state in which a cell has an abnormal number of chromosomes and is dysfunctional as a result.

Like all forms of cellular malfunction, there is more of it in old tissues. But is it significant in aging? In recent years researchers demonstrated that one way of reducing aneuploidy is to boost levels of BubR1, which normally declines with age.

As a genetic alteration this extends life in mice, but of course has a range of other effects beyond influencing aneuploidy, so the meaningful mechanism in this extension of healthy life isn't clearly defined. This is the case for many ways to slow aging in mice. Here is a piece on another group studying aneuploidy in aging.

Read More https://www.fightaging.org/archives/2015/01/aneuploidy-and-aging.php

Picking the Wrong Path for Bad Reasons - Wednesday, January 21, 2015
As regular readers know, I advocate for the development of treatments for aging based on periodic repair of the low-level cellular and molecular damage that causes aging. There is at least one detailed plan of action on how to produce the necessary treatments, the Strategies for Engineered Negligible Senescence (SENS) research proposals.

Enough is known to work on this with a good expectation of success. Outside of factions within the stem cell research community this is still at this time a minority path in the scientific community, however. Most research groups are much more interested in developing a greater understanding of the fine details of metabolism so as to alter it in order to slow down aging.

Unfortunately this latter path is nowhere near the point of producing a working plan, and it has proven to be enormously expensive and time consuming to investigate even tiny slices of the necessary reach of knowledge. See the much hyped past decade of research on sirtuins, for example, that has consumed the cost of implementing SENS in the laboratory several times over without producing any meaningful treatment.

In this piece, the author chooses the hard, slow, expensive, largely unknown path of altering the fundamental operation of metabolism as the better way forward for egalitarian reasons - that a one-time alteration that slows aging is better than a frequent treatment to repair aging because it is somehow more equal, or less prone to ongoing costs.

This seems silly. For one, even setting aside the much greater difficulty and time required to develop means of altering metabolism, that approach cannot produce rejuvenation as it only slows down the pace of damage accumulation. Thus it cannot help the old, and it cannot extend healthy life indefinitely.

Repair therapies can in principle achieve these goals, it's just a matter of how well they repair the damage. When it comes to costs, the mature evolution of SENS-like repair treatments would be a mass-produced infusion given by a bored clinician once every twenty years or so. Mass produced infusions such as TNF inhibitors today cost a few thousand, even in the dysfunctional US medical system. So this seems like another example of death for everyone before even the vague possibility of inequality for someone, a position sadly prevalent in many areas of our society.

Read More https://www.fightaging.org/archives/2015/01/picking-the-wrong-path-for-bad-reasons.php

A Look at Parabiosis Research - Thursday, January 22, 2015
Parabiosis involves joining together the circulatory systems of two individuals.

Joining together an old and a young mouse has proved to be very instructive now that researchers can measure quite detailed aspects of cellular biology, and in recent years it has been used to investigate age-related changes that take place in levels of various proteins in the blood. Some of those proteins can alter cellular behavior in important ways, and manipulating them in old individuals can improve degraded tissue function. This article provides a recent history of this research and hopes for the near future.

Read More https://www.fightaging.org/archives/2015/01/a-look-at-parabiosis-research.php

Blood-Brain Barrier Damage in Aging - Thursday, January 22, 2015
Like all tissues, those of the blood-brain barrier in blood vessel walls deteriorate due to the cellular and molecular damage of aging. Researchers here correlate that deterioration with progressive cognitive impairment, further reinforcing existing data on the contribution of blood vessel functional decline to age-related damage in the brain.

Read More https://www.fightaging.org/archives/2015/01/blood-brain-barrier-damage-in-aging.php

An Interview with Valter Longo on Intermittent Fasting - Friday, January 23, 2015
Researcher Valter Longo is presently working on, among other things, packaging up intermittent fasting as a treatment with the sort of rigor needed to get it through clinical trials with the FDA.

The work leading up the clinical trials involved putting numbers to the short term benefits provided by fasting: how often and how long must someone fast in order to achieve specific changes in biomarkers of health, and how long do those effects last?

The data will be useful for people who practice intermittent fasting as a health strategy, moving the state of scientific support for this strategy closer to that existing for the practice of calorie restriction with optimal nutrition.

Read More https://www.fightaging.org/archives/2015/01/an-interview-with-valter-longo-on-intermittent-fasting.php

A Novel Method of Telomere Extension - Friday, January 23, 2015
Telomeres are the protective caps of repeated DNA sequences found at the end of chromosomes. Telomere length is a part of the regulatory system that prevents cells from dividing indefinitely: a little length is lost with each cell division, and a cell destroys itself or otherwise ceases to divide when its telomeres become too short.

In stem cell populations, responsible for delivering fresh batches of long-telomere daughter cells into tissues to replace those lost due to reaching the limits of replication, the enzyme telomerase is active to maintain lengthy telomeres by adding extra repeating sequences to the ends.

Cancer cells also make use of telomerase or other methods of lengthening telomeres in order to maintain their ability to rapidly and continually divide, but this process isn't normally active in the majority of the cells in the body. Average telomere length in white blood cells tends to decrease with age and illness, and this is really a proxy measure that blurs some combination of cell division rates and stem cell activity.

Researchers have lengthened healthy life in mice by boosting the activity of telomerase via genetic engineering, though it is still the case that there is no definitive experiment to show which of the possible mechanisms causes this life extension. Is it a matter of more stem cell activity, some secondary effect of having long telomeres such as increased cell life span, or another aspect of telomerase, such as its influence on mitochondrial biology?

There is considerable interest in the research community in continuing to explore what might happen when telomeres are lengthened, and so it is inevitable that better methods of lengthening will be developed.

Read More https://www.fightaging.org/archives/2015/01/a-novel-method-of-telomere-extension.php
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DISCLAIMER:  News summaries are reported by third parties, and there is no guarantee of accuracy. This newsletter is not meant to substitute for your personal due diligence and is not to be taken as medical advice. For originating report, please see www.fightaging.org/

David A. Kekich
Maximum Life Foundation
www.MaxLife.org

"Where Biotech, Infotech and Nanotech
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