Immortal Animals Defy Aging

Healthy Life Extension

Funding Aging Research

Immortal Animals Defy Aging

posted on March 6th, 2012

Dear Future Centenarian,

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Researchers from The University of Nottingham have demonstrated how a species of flatworm overcomes the aging process to be potentially immortal. 

You might say, œBig deal! What do worms have to do with me?

Maybe plenty, once we extrapolate what we learn from worms and apply it to humans.

The discovery, published in the Proceedings of the National Academy of Sciences, and may shed light on the possibilities of alleviating aging and age-related characteristics in human cells.
Planarian worms have amazed scientists with their apparently limitless ability to regenerate. Researchers have been studying their ability to replace aged or damaged tissues and cells in a bid to understand the mechanisms underlying their longevity.

"Usually when stem cells divide -­ to heal wounds, or during reproduction or for growth -­ they start to show signs of aging. This means that the stem cells are no longer able to divide and so become less able to replace exhausted specialized cells in the tissues of our bodies. Our aging skin is perhaps the most visible example of this effect. Planarian worms and their stem cells are somehow able to avoid the aging process and to keep their cells dividing."

One of the events associated with aging cells is related to telomere length. In order to grow and function normally, cells in our bodies must keep dividing to replace cells that are worn out or damaged. During this division process, copies of the genetic material must pass on to the next generation of cells. The genetic information inside cells is arranged in twisted strands of DNA called chromosomes. At the end of these strands is a protective 'cap' called a telomere. Telomeres have been likened to the protective end of a shoelace which stops strands from fraying or sticking to other strands.
Each time a cell divides the protective telomere 'cap' gets shorter. When they get too short, the cell loses its ability to renew and divide. In an immortal animal we would therefore expect cells to be able to maintain telomere length indefinitely so that they can continue to replicate. Dr Aboobaker predicted that planarian worms actively maintain the ends of their chromosomes in adult stem cells, leading to theoretical immortality.

Previous work, leading to the award of the 2009 Nobel Prize for Physiology or Medicine, had shown that telomeres could be maintained by the activity of an enzyme called telomerase. In most sexually reproducing organisms, the enzyme is most active only during early development. So as we age, telomeres start to reduce in length.

This project identified a planarian version of the gene coding for this enzyme and turned down its activity. They found that asexual worms dramatically increase the activity of this gene when they regenerate, allowing stem cells to maintain their telomeres as they divide to replace missing tissues.

Sexually reproducing planarian worms do not appear to maintain telomere length in the same way. But both appear to have an indefinite regenerative capacity.

Dr. Aboobaker concluded, "Our data satisfy one of the predictions about what it would take for an animal to be potentially immortal, and that it is possible for this scenario to evolve. The next goals for us are to understand the mechanisms in more detail and to understand more about how you evolve an immortal animal."

Prof. Douglas Kell, BBSRC Chief Executive, said, "This exciting research builds strong foundations for improving health and potentially longevity in other organisms, including humans."

Long Life,
David Kekich


The membrane pacemaker hypothesis suggests that longevity differences between species are largely determined by the resistance to oxidative damage exhibited by important cell membranes - such as those in mitochondria.

Here is some evidence to suggest that this holds up within a species too: "Membrane unsaturation plays an important role in the aging process and the determination of inter-species animal longevity. Furthermore, the accumulation of oxidation-derived molecular damage to cellular components particularly in the nervous and immune systems over time leads to homeostasis loss, which highly influences age-related morbidity and mortality. In this context, it is of great interest to know and discern the degree of membrane unsaturation and the steady-state levels of oxidative damage in both physiological systems from long-lived subjects.

In the present work, adult (28‰Â±‰4 weeks), old (76‰Â±‰4 weeks) and exceptionally old (128‰Â±‰4 weeks) BALB/c female mice were used. Brain and spleen were analysed for membrane fatty acid composition and specific markers of protein oxidation, glycoxidation and lipoxidation damage .The results showed significantly [higher membrane resistance to lipid peroxidation and lower lipoxidation-derived molecular damage brain and spleen in] exceptionally old animals when compared to old specimens .

In addition, the higher levels of the glycoxidation-derived marker observed in exceptionally old animals, as well as in adult mice, could be considered as a good indicator of a better bioenergetic state of these animals when compared to the old group. In conclusion, low lipid oxidation susceptibility and maintenance of adult-like protein lipoxidative damage could be key mechanisms for longevity achievement."

An open access commentary at Impact Aging: "There is a lively discussion going on as to whether oxidative stress is or is not a cause of (accelerated) aging, fuelled to a significant extent by the finding from Arlan Richardson's group that mice heterozygous for the mitochondrial superoxide dismutase SOD2 showed increased oxidative stress, increased cancer incidence but not accelerated ageing.

A new twist to this story was introduced recently when it was shown that connective tissue-specific SOD2 knockouts developed multiple signs of progeria including short lifespan, associated with up-regulation of the cell senescence marker p16INK4A. Mitochondrially generated oxidative stress is both an established cause and a relevant consequence of cell senescence, frequencies of senescent cells in connective tissue increase during mice aging, and destruction of senescent cells can 'cure' some age-related tissue dysfunction.

A paper by Judith Campisi's and Simon Melov's groups recently published in Aging now further explores the connection between oxidative stress, cell senescence and aging. The authors demonstrate that mitochondrial dysfunction occurs in the epidermis of old (2 years) mice. These data enforce two central hypotheses in the field, namely that of mitochondrial dysfunction as a cause of cell senescence, and of cell senescence as a relevant contributor to mammalian aging. However, a fascinating question remains: Is it really Reactive Oxygen Species (ROS) arising from mitochondria that promote cellular senescence in this model?"

We are far from the first generation to have looked at the state of science and postulated that we can significantly extend human life span through some specific means - but we are the first generation to have possession of the necessary scientific knowledge to be correct in our evaluation.

That we have this knowledge is why you can't just look at the long history of predictions of longevity and say "we're just another generation that will be disappointed - it's all more of the same." The past is a great place to look if you want to predict the future of politics, but a terrible resource for predicting the future of technology. There is an enormous difference between the state of life science of today and the nascent biotechnology of the 1970s and advocates like Timothy Leary - and not to mention the science of the early 20th century as is referenced in this article: "It might seem as if a magic [longevity-enhancing] pill isn't so far off. But before we get too cheery about the prospects for these discoveries, it's useful to be reminded of the many longevity 'breakthroughs' that have come and gone in the past.

One such potential advance was hailed in the November 1929 issue of Technology Review, in an essay called 'Forestalling Death: The Cow's Contribution to Human Longevity' In the previous 125 years, Tobey observed, average life span had risen from the low 30s to the upper 50s. This was primarily due to reductions in infectious disease and in the infant death rate.

It wasn't enough to simply reduce a threat such as infectious disease - it was imperative that we find something we could add to our lives, or maybe simply increase our intake of something we were already consuming. He felt recent research might have uncovered just such a substance. He pointed to recent experiments at Columbia University, wherein one set of rats had been given an 'adequate diet' of one-sixth dried whole milk and five-sixths whole wheat. An 'optimal diet' group, meanwhile, received double the milk and less wheat. The average duration of life was almost exactly ten percent greater in those subjects receiving the optimal diet.

Is it possible that we have had the fountain of youth within our grasp throughout the ages that man has been seeking this liquid phantasm? Milk has always been recognized as the one most nearly perfect food, but apparently it possesses hitherto undreamed of virtues." And so on: the end result is more of the oral fixation that seems to so dominate our culture - in the popular imagination everything of significance must be something that we put in our mouths and consume. Most important medicine, of course, is nothing of the sort.

The core point of SENS, the Strategies for Engineered Negligible Senescence, is explained in this short interview: "Could you elaborate on the idea mentioned on SENS: that it isn't necessary to know, from an 'engineering' perspective, everything about the degenerative processes that occur at the cellular level in order to treat aging in the way you envision?

The basic point we're making there is to contrast the regenerative approach with the more traditional idea of trying to make metabolism create molecular and cellular damage more slowly. In order to do the latter, we would need to understand our biology massively better than we do at present, so as to avoid creating unforeseen side-effects. By contrast, with the regenerative approach we don't need to know much about how damage comes about: it's enough just to characterize the damage itself, so as to figure out ways to repair it.

We're effectively sidestepping our ignorance of metabolism. Rejuvenation biotechnologies are simply regenerative therapies that pre-empt the diseases and disabilities of old age. They consist of molecular, cellular or whole-organ interventions that restore the structure of the target to something like how it was in early adulthood.

This includes a variety of stem cell therapies, and also tissue engineering to create artificial organs. At SENS Foundation we don't work much on those types of therapy, because they're being very capably pursued elsewhere; rather, we focus on the more neglected but equally vital components of this 'divide-and-conquer' approach to combating aging. For example, we have a large project aimed at eliminating 'molecular garbage' from cells - indigestible material whose accumulation leads to diseases like atherosclerosis and macular degeneration - by introducing non-human enzymes to augment the body's natural ability to break down unwanted by-products of metabolism."

STEM CELL ACTIVITY AND MEMORY Tuesday, February 28, 2012
Progress in stem cell medicine may lead to ways to restore the capacity for memory lost with aging by intervening in the activity of neural stem cells: researchers "have discovered an answer to the long-standing mystery of how brain cells can both remember new memories while also maintaining older ones.

They found that specific neurons in a brain region called the dentate gyrus serve distinct roles in memory formation depending on whether the neural stem cells that produced them were of old versus young age. In animals, traumatic experiences and aging often lead to decline of the birth of new neurons in the dentate gyrus. In humans, recent studies found dentate gyrus dysfunction and related memory impairments during normal aging. In the study, the authors tested mice in two types of memory processes. Pattern separation is the process by which the brain distinguishes differences between similar events, like remembering two Madeleine cookies with different tastes.

In contrast, pattern completion is used to recall detailed content of memories based on limited clues, like recalling who one was with when remembering the taste of the Madeleine cookies. Neuroscientists have long thought these two opposing and potentially competing processes occur in different neural circuits. The dentate gyrus, a structure with remarkable plasticity within the nervous system and its role in conditions from depression to epilepsy to traumatic brain injury - was thought to be engaged in pattern separation and the CA3 region in pattern completion. Instead, [researchers] found that dentate gyrus neurons may perform pattern separation or completion depending on the age of their cells."

A range of research currently underway focuses on limited but potentially effective ways to reprogram the immune system, so as to work around naturally occurring damage or compromise, or to boost immune system activity when it would do the most good. It's worth keeping an eye on the AIDS research community on this topic, as there are a few broad structural similarities between the aged immune system and the AIDS-compromised immune system:

"researchers report on a promising new technique that potentially could turn immune system killer T cells into more effective weapons against infections and possibly cancer. The technique involves delivering DNA into the immune system's instructor cells. The DNA directs these cells to overproduce a specific protein that jumpstarts important killer T cells. These killer cells are typically repressed in patients who have HIV or cancer. Their technique proved effective in jumpstarting defective immune systems in immuno-compromised mice and in human killer T cells taken from people with HIV.

In the study, snippets of DNA were delivered into skin instructor cells by a device known as a gene gun. The DNA directed the instructor cells to produce specific proteins, which act like molecular keys. When CD8 T cells interact with the instructor cells, the keys unlock the CD8 T cells' killer properties - jumpstarting them to go out and kill pathogens and cancer cells.

With the use of this technique, the killer T cells would not need the assistance of helper T cells. So even if a tumor were to put the helper T cells in a suppressive cage, the killer T cells would still be able to go out and kill cancer cells. Researchers expect that future studies using the technique will make it applicable to many diseases, including cancer."

Calorie restriction slows more or less every measure of aging, and here is another - a small study to measure decline in the nervous system cells that control a portion of the intestines: "The objective of this study was to evaluate the effects of caloric restriction (CR) on myenteric neurons in the duodenum of Wistar rats during aging.

Thirty rats were divided into three groups: the C group (six-month-old animals that were fed a normal diet from weaning until six months of age), the SR group (18-month-old animals that were fed a normal diet from weaning until 18 months of age) and the CR group (18-month-old animals that were fed a 30% CR diet after six months of age). The neurons were counted, and the cell body areas were measured. Aging was associated with neuronal loss in the SR group, which was minimized by caloric restriction in the CR group. Thus, CR had a protective effect on myenteric neurons during aging."

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