The second volume of the new open access journal Pathobiology of Aging and Age-related Disease is available online. I thought I'd point out one of the papers, which argues that the biology of long-lived mouse species should be considered evidence for the importance of chronic inflammation in determining life span.

Growth hormone, inflammation and aging

Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1) constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor / growth hormone binding protein knockout (GHRKO) mice characterized by GH resistance live significantly longer than genetically normal animals.

During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines.

This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.

Regular readers will recall that there is a mountain of evidence to link aging and chronic inflammation. If you have higher levels of inflammation, you will have a worse - and usually shorter - time ahead. It causes damage, and that damage adds up; the easiest way in younger life to raise inflammation levels is to become fat, as visceral fat tissue works a number on your metabolism. But everyone's immune system runs off the rails given time, falling into a state wherein it is constantly roused but increasingly ineffective in its designated jobs. Many of the aspects of aging are clearly connected to immune system decline: raised levels of inflammation, increased numbers of senescent cells, increased risk of cancer, and more.

This all argues for some form of safer, more mature version of the immune system reboot therapies that can presently be accomplished, but are not available outside of trials at this time. A large fraction of the immune system's failure with age stems from structural issues: it has evolved to be very, very good at its job in early life, but at the cost of inevitably and predictably failing as it runs out of capacity later on.

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.

But if the slate could be wiped clean (achieved by chemotherapy at the present time, which is far from ideal) and the immune system repopulated (using stem cells to generate a population of patient-matching immune cells), then this issue vanishes, and people could benefit from a strong immune system for decades longer than is presently the case. That would likely make a significant difference to the course of later life, even in the absence of other advances in medical technology.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Researchers make paralyzed rats walk through a mix of chemical stimulation and structured physical therapy; only a little regrowth in the spine occurs, but the lower spinal column can take over some of the lost functionality under the right circumstances: "a severed section of the spinal cord can make a comeback when its own innate intelligence and regenerative capacity is awakened. ... After a couple of weeks of neurorehabilitation with a combination of a robotic harness and electrical-chemical stimulation, our rats are not only voluntarily initiating a walking gait, but they are soon sprinting, climbing up stairs and avoiding obstacles when stimulated. ... until now the spinal cord expressed so little plasticity after severe injury that recovery was impossible. ... under certain conditions, plasticity and recovery can take place in these severe cases - but only if the dormant spinal column is first woken up. To do this, [researchers] injected a chemical solution of monoamine agonists into the rats. These chemicals trigger cell responses by binding to specific dopamine, adrenaline, and serotonin receptors located on the spinal neurons. This cocktail replaces neurotransmitters released by brainstem pathways in healthy subjects and acts to excite neurons and ready them to coordinate lower body movement when the time is right. ... Five to 10 minutes after the injection, the scientists electrically stimulated the spinal cord with electrodes implanted in the outermost layer of the spinal canal, called the epidural space. ... a stimulated rat spinal column - physically isolated from the brain from the lesion down - developed in a surprising way: It started taking over the task of modulating leg movement, allowing previously paralyzed animals to walk over treadmills. These experiments revealed that the movement of the treadmill created sensory feedback that initiated walking - the innate intelligence of the spinal column took over, and walking essentially occurred without any input from the rat's actual brain. This surprised the researchers and led them to believe that only a very weak signal from the brain was needed for the animals to initiate movement of their own volition. ... newly formed fibers bypassed the original spinal lesion and allowed signals from the brain to reach the electrochemically-awakened spine. And the signal was sufficiently strong to initiate movement over ground."

Link: http://www.sciencedaily.com/releases/2012/05/120531145714.htm

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

There is death and then there is information theoretic death - a person who is cryopreserved is a good deal less dead than someone who went to the grave. The fine structure and data of the mind still exist, in a cold-stored stasis, and thus might be restored through foreseeable future technology. Here are some notes on the legal situation with respect to cryopreserved people: "This article series seeks to compare the legal protection of cryonics patients under their present legal status to the legal protection which would be afforded them if they were recognized as persons under the law, thinking ahead to such future time as it becomes reasonably possible to put legal and political pressure towards enhanced legal recognition of cryonics patients. The previous article examined laws that directly affect what happens to a person's body after legal death, both in the period immediately after declaration of legal death, and indefinitely thereafter. We saw that the amount of prospective autonomy a person is permitted in this regard can vary significantly from jurisdiction to jurisdiction, with more or less consideration afforded to the wishes of the person's next of kin, religious beliefs, societal norms and other public interests. Two other legal structures which can and are used by cryonicists to promote the success and timeliness of cryopreservation, maintenance, and resuscitation are wills and trusts."

Link: http://www.evidencebasedcryonics.org/2012/05/05/legal-protection-of-cryonics-patients-part-2/

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Published at Impact Aging you'll find descriptions of the presentations given at the Second International Conference on the Genetics of Aging and Longevity, held in Moscow recently. It's a good representative sample if you'd like to know what the mainstream of aging and longevity science looks like. What I wanted to draw your attention to was this presentation and question:

Vladimir Anisimov (N.N. Petrov Research Institute of Oncology, Russia) in his presentation "Do we really have a medicine against aging?" showed results of experiments on effects of antidiabetic biguanides and rapamycin on biomarkers of aging, life span, spontaneous and chemically-induced carcinogenesis in outbred, inbred and transgenic HER-2/neu mice and in rats.

The mTOR inhibitor rapamycin prevents age-related weight gain, decreases rate of aging, increases life span and decreases carcinogenesis in transgenic HER-2/neu cancer-prone mice. Rapamycin dramatically delayed tumors onset, decreased a number of tumors per animal and tumor size. Lifelong administration of rapamycin extends lifespan in female 129/Sv mice characterized by normal mean lifespan of 2 years. Importantly, rapamycin was administrated intermittently (every other 2 weeks) starting from the age of 2 months. Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors) and delayed spontaneous cancer. 22.9% of rapamycin-treated mice survived the age of death of the last mouse in control group.

...

Treatment of female outbred SHR mice with metformin started at the age of 3 months increased mean life span by 14% and maximum life span by 1 month. Same treatment started at the age of 9 months insignificantly increased mean life span by 6%, whereas treatment started at the age of 15 months failed to increase life span. When started at the age of 3 and 9 months, metformin delayed time of the first tumor detection by 22% and 25%, correspondingly.

...

These results suggest that both metformin and rapamycin may be useful in prevention of cancer and extension of lifespan when used in rational and appropriate ages, doses and schedules.

Asking and attempting to answer questions like "does medicine for aging exist" is going to make you unpopular in some quarters no matter how you answer. The large and energetic "anti-aging" marketplace, eternally plagued by the dishonesty of its bad apples, has been crying "yes, yes, get your treatments for aging here" for about as long as mankind has existed. The invention of fraud no doubt followed the discovery of the concepts of value and trade by only a few heartbeats. When no-one could in fact do much of anything about aging, one might say "so what?" Fraud and lies about extending life were no different then than fraud and lies about anything else that didn't exist and couldn't be made to exist - such as the ownership rights to certain bridges, for example.

In these later days of science and reason, however, in which we stand upon the verge of building real and meaningful ways to treat aging, that commercial "anti-aging" market is a millstone around the necks of the scientific community. It is in fact a large part of the reason why up until very recently the aging research field was extremely hostile towards anyone talking seriously about treating aging.

So you are going to see care taken when people in the scientific community speak on such topics. For my part, I think it's completely fair to put forward that, by modern standards of drug development, you could point to rapamycin and metformin and say "these are candidate treatments for aging." By this I mean that they are likely to produce minimal benefits, have potentially ugly side-effects, and are not yet really tested for that specific usage in humans - which describes both a fair chunk of the drug discovery pipeline and many drugs out there in widespread use. We are willing to call those therapies for the conditions they are used to treat.

But let's be clear: as prospective therapies for aging, these drugs are terrible. Truly bad. They are far worse than exercise or calorie restriction - they produce lesser benefits and you get unpleasant side-effects into the bargain. So given all of that I don't think it is unreasonable to say that yes, treatments for aging exist at the present time, and they are awful.

(It is worth pointing out that a gain in life span of 20% in mice is not all that in the grand scheme of things. Exercise can do better, and calorie restriction does twice as well. Further, it is not seriously expected that any gain of 20% in life span in mice through metabolic alteration will translate to a similarly meaningful gain in human life span - which has to do with many of the differences that cause us to be long-lived already for our size. For example, calorie restriction is not thought to be capable of producing more than a few years of gain in maximal human life span, even while it produces large gains in health and resistance to age-related disease).

The real path to the future, to my eyes, is to skip over all of this longevity-enhancing drug discovery nonsense, interesting though it may be, and focus on repair of specific forms of cellular and molecular damage - such as the detailed methodologies proposed in the SENS vision. If SENS or similar programs for research and development fail to become a dominant approach to longevity science, and the foreseeable future thus remains a heaping helping of more longevity-enhancing drug discovery nonsense, then therapies for aging will continue to be generally awful.

I consider it to be unfortunate that the bulk of the pro-longevity aging research camp is focused on an inefficient path forward that will in the end lead to lesser benefits. It is their belief that this is the only practical way ahead: a laborious slog towards complete understanding of aging and metabolism, followed by an even more complex navigation through re-engineering that metabolism to age more slowly. The sheer scale and difficulty of that task is why many scientists feel that meaningful engineered longevity - more healthy years through science - is a long way away indeed.

...

It is likely to be easier and less costly to produce rejuvenation therapies than to produce a reliable and significant slowing of aging. A rejuvenation therapy doesn't require a whole new metabolism to be engineered, tested, and understood - it requires that we revert clearly identified changes to return to a metabolic model that we know works, as it's used by a few billion young people already. Those rejuvenation therapies will be far more effective than slowing aging in terms of additional years gained, since you can keep coming back to use them again and again. They will also help the aged, who are not helped at all by a therapy that merely slows aging.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Researchers "have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington's disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models. ... Induced pluripotent stem cells (iPSCs) can be genetically engineered from human somatic cells such as skin, and can be used to model numerous human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory. In the current study, experimental animals with damage to a deep brain structure called the striatum (an experimental model of HD) exhibited significant behavioral recovery after receiving transplanted iPS cells. The researchers hope that this approach eventually could be tested in patients for the treatment of HD. ... the transplanted cells will be genetically identical to the patient and therefore no medications that dampen the immune system to prevent graft rejection will be needed. ... transplanted iPSCs initially formed neurons producing GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system, which plays a critical role in regulating neuronal excitability and acts at inhibitory synapses in the brain. GABAergic neurons, located in the striatum, are the cell type most susceptible to degeneration in HD."

Link: http://www.vai.org/News/News/2012/05_29_Huntingtons.aspx

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Researchers "have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington's disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models. ... Induced pluripotent stem cells (iPSCs) can be genetically engineered from human somatic cells such as skin, and can be used to model numerous human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory. In the current study, experimental animals with damage to a deep brain structure called the striatum (an experimental model of HD) exhibited significant behavioral recovery after receiving transplanted iPS cells. The researchers hope that this approach eventually could be tested in patients for the treatment of HD. ... the transplanted cells will be genetically identical to the patient and therefore no medications that dampen the immune system to prevent graft rejection will be needed. ... transplanted iPSCs initially formed neurons producing GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system, which plays a critical role in regulating neuronal excitability and acts at inhibitory synapses in the brain. GABAergic neurons, located in the striatum, are the cell type most susceptible to degeneration in HD."

Link: http://www.vai.org/News/News/2012/05_29_Huntingtons.aspx

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Via EurekAlert!: researchers "studied 713 women aged 70 to 79 years who took part in the Women's Health and Aging Studies. This study was designed to evaluate the causes and course of physical disability in older women living in the community. ... A number of studies have measured the positive impact of exercise and healthy eating on life expectancy, but what makes this study unique is that we looked at these two factors together. ... Researchers found that the women who were most physically active and had the highest fruit and vegetable consumption were eight times more likely to survive the five-year follow-up period than the women with the lowest rates. ... Study participants' physical activity was measured through a questionnaire that asked the amount of time the spent doing various levels of physical activity, which was then converted to the number of calories expended. The women were then followed up to establish the links between healthy eating, exercise and survival rates. Key research findings included: More than half of the 713 participants (53%) didn't do any exercise, 21% were moderately active, and the remaining 26% were in the most active group at the study's outset. During the five-year follow up, 11.5% of the participants died. Serum carotenoid levels were 12% higher in the women who survived and total physical activity was more than twice as high. Women in the most active group at baseline had a 71% lower five-year death rate than the women in the least active group. Women in the highest carotenoid group at baseline had a 46% lower five-year death rate than the women in the lowest carotenoid group. When taken together, physical activity levels and total serum carotenoids predicted better survival."

Link: http://www.eurekalert.org/pub_releases/2012-05/w-eaa053012.php

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm