As I'm sure you all know by now, mitochondria are swarming powerplants within the cell, descendants of symbiotic bacteria that bear their own DNA separate from the DNA in the cell nucleus. Mitochondrial DNA provides the blueprints for proteins making up the machinery of a mitochondrion, but it isn't as well protected or as well repaired as nuclear DNA. Given that a lot of reactive compounds are funneled through mitochondria in the processes that keep a cell powered, it is only to be expected that mitochondrial DNA becomes progressively more damaged over time. The range of mechanisms that have evolved to deal with that damage cannot keep up over the long term, and as a result a small but significant portion of our cells fall into ruin on the way to old age, becoming populated by dysfunctional, damaged mitochondria, and causing a great deal of harm to surround tissues and bodily systems by exporting a flood of reactive biochemicals. You can read a longer and more detailed description of this process back in the Fight Aging! archives.

So that is one side of the issue of mitochondrial DNA damage and its contribution to degenerative aging - and that in and of itself would be more than enough to make mitochondrial repair biotechnologies a research priority. There are many different potential ways of fixing or rendering irrelevant mitochondrial DNA damage, and allowing mitochondria to continue to function as well as they did at birth for an indefinite period of time. The sooner one of them is developed into a working therapy the better.

In considering mitochondrial damage there is another, more straightforward process at work, however. Many types of cell normally operate fairly close to the limit of the power provided by their mitochondria, including important cell populations in the brain and nervous system. As mitochondrial DNA damage accumulates with age, power production - meaning the pace at which adenosine triphosphate (ATP) is produced - falls off and cells either die or malfunction far more often than they did in youth. This is outlined in a recent open access review paper:

In aerobic cells the majority of ATP is produced by oxidative phosphorylation. This process takes place in the mitochondria where electrons that are donated from the Krebs cycle are passed through the four complexes (complex I-IV) comprising the electron transport chain (ETC), eventually reducing oxygen and producing water.

...

Many cells operate at a basal level that only requires a part of their total bioenergetic capability. The difference between ATP produced by oxidative phosphorylation at basal and that at maximal activity is termed "spare respiratory capacity" or "reserve respiratory capacity" ... Under certain conditions a tissue can require a sudden burst of additional cellular energy in response to stress or increased workload. If the reserve respiratory capacity of the cells is not sufficient to provide the required ATP affected cells risk being driven into senescence or cell death.

...

In this paper we hypothesize that mitochondria contributes to aging and age-related pathologies through a life-long continued decrease of the respiratory reserve capacity. The decrease sensitizes high energy requiring tissues to an exhaustion of the reserve respiratory capacity. This increases the risk of a range of pathologies that correspondingly are known to be age-related. Through a review of the effects of aging on the regulation of oxidative phosphorylation, we wish to substantiate this hypothesis. In addition, by using brain, heart, and skeletal muscle as examples, we will review how an age-related decrease of the reserve respiratory capacity is implicated in a variety of pathologies in the affected tissues.

Interestingly, there is a good case for arguing that it isn't just damage to mitochondria DNA (mtDNA) that reduces levels of power production in a cell's mitochondria - there are other changes taking place that turn down the dial, which in the absence of more definitive knowledge as to their causes could be classified either as programmed aging or as a programmed response to stochastic damage in other cellular systems:

Cumulative damage to the mtDNA is however, not the only contributor to the age-related decline of oxidative phosphorylation. Transcriptional profiling has revealed different regulation of nuclear genes encoding important peptides for oxidative phosphorylation when comparing young to old.

Either way, those mitochondria still need fixing. The biotechnologies capable of that job are on the horizon, and would be coming closer more rapidly if those involved in the work had a greater level of funding.

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

Steady progress in medicine has led to an ongoing reduction in many age-related conditions over the past few decades. Such as this, for example: "Today's senior citizens are reporting fewer visual impairment problems than their counterparts from a generation ago, according to a new [study]. Improved techniques for cataract surgery and a reduction in the prevalence of macular degeneration may be the driving forces behind this change, the researchers said. ... From 1984 until 2010, the decrease in visual impairment in those 65 and older was highly statistically significant. There was little change in visual impairments in adults under the age of 65. ... The [ study] shows that in 1984, 23 percent of elderly adults had difficulty reading or seeing newspaper print because of poor eyesight. By 2010, there was an age-adjusted 58 percent decrease in this kind of visual impairment, with only 9.7 percent of elderly reporting the problem. There was also a substantial decline in eyesight problems that limited elderly Americans from taking part in daily activities, such as bathing, dressing or getting around inside or outside of the home ... there are three likely reasons for the decline: (a) Improved techniques and outcomes for cataract surgery. (b) Less smoking, resulting in a drop in the prevalence of macular degeneration. (c) Treatments for diabetic eye diseases are more readily available and improved, despite the fact that the prevalence of diabetes has increased "

Link: http://www.northwestern.edu/newscenter/stories/2012/06/seniors-eyesight.html

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

Cryonics provider Alcor is holding a 40th anniversary conference in October, and the presently announced program looks much like this: "Sebastian Seung on testing how well cryopreservation (and alternatives) preserves the connectome. Todd Huffman on brain scanning. Panel discussion on long-term financial planning, including investing strategies, inflation protection, and personal trusts. Aschwin and Chana de Wolf from Advanced Neural Biosciences on advances in cryonics-relevant research. Greg Fahy from 21st Century Medicine on advances in cryoprotection. Aubrey de Grey from the SENS Foundation. Joshua Mitteldorf on programmed aging. Anders Sandberg on 'Handling the unknowable and undecidable: rational decision making about future technology.' Catherine Baldwin on advances at Suspended Animation. Panel on medical monitoring devices for improving your chances of a quick response in case of a critical physiological failure. Max More on how to improve your prospects for an optimal cryopreservation."

Link: http://www.alcor.org/conferences/2012/

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

If I mention medical nanorobotics, you might think of the designs put forward by Robert Freitas and others: molecular machines constructed largely from carbon that bear little relation to the cells and cellular system they are intended to interact with. Or you might think of the crude forerunners of those designs presently being tested in the laboratory, such as targeted nanoparticles and nanocontainers used to deliver drug compounds more precisely to where they are needed.

But you and I are built out of nanorobots: each of our cells is effectively a structured collection of cooperating, programmable nanoscale robots. They are evolved rather than designed, but still represent a vast preexisting parts library for researchers interested in building the first generation of medical nanorobots. While it is true that there are good reasons for reinventing this wheel, such as gaining far greater performance than is possible from anything similar to our present biology, given that time is of critical importance in developing the next generation of medicine, why not use these existing designs?

It seems likely that the first medical nanorobots (well, microrobots in this case) will be highly modified or even completely artificial cells. Why ignore the working blueprint that's right in front of you, after all?

Researchers are already building the prototypes, far more advanced than simple targeted nanoparticles. Here, for example, is news of progress towards nanofactories. These are programmable, artificial bacteria-like entities that can be set up to manufacture specific drug compounds in response to their local environment, or to signals from outside the body such as light or ingested chemicals.

Scientists are reporting an advance toward treating disease with minute capsules containing not drugs - but the DNA and other biological machinery for making the drug. ... development of nanoscale production units for protein-based drugs in the human body may provide a new approach for treating disease. These production units could be turned on when needed, producing medicines that cannot be taken orally or are toxic and would harm other parts of the body. Until now, researchers have only done this with live bacteria that were designed to make proteins at disease sites. But unlike bacterial systems, artificial ones are modular, and it is easier to modify them. That's why [this research group] developed an artificial, remotely activated nanoparticle system containing DNA and the other "parts" necessary to make proteins, which are the workhorses of the human cell and are often used as drugs.

They describe the nanoscale production units, which are tiny spheres encapsulating protein-making machinery like that found in living cells. The resulting nanoparticles produced active proteins on demand when the researchers shined a laser light on them. The nanoparticles even worked when they were injected into mice, which are stand-ins for humans in the laboratory, producing proteins when a laser was shone onto the animals.

The sky is the limit once biotechnology really takes off - and we're still in the early stages of this phase of progress. Much more is yet to come.

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

Why not aim to improve on blood? Its primary function is to carry oxygen, and it has evolved to do the bare minimum necessary on this front - separate any part of the body from a supply of oxygen for a minute or so and you're in trouble. It would be nice, for example, to have blood with a reserve capacity of a few hours, achieved using nanomachines that store the surplus oxygen that the body doesn't otherwise extract from air breathed in. Even if the heart stopped or blood stopped flowing in some vital tissue, you'd have those few hours to seek medical help. Here is a gentle first step towards the technologies of better blood: researchers "designed tiny, gas-filled microparticles that can be injected directly into the bloodstream to quickly oxygenate the blood. The microparticles consist of a single layer of lipids (fatty molecules) that surround a tiny pocket of oxygen gas, and are delivered in a liquid solution. ... report that an infusion of these microparticles into animals with low blood oxygen levels restored blood oxygen saturation to near-normal levels, within seconds. When the trachea was completely blocked - a more dangerous 'real world' scenario - the infusion kept the animals alive for 15 minutes without a single breath, and reduced the incidence of cardiac arrest and organ injury. The microparticle solutions are portable and could stabilize patients in emergency situations, buying time for paramedics, emergency clinicians or intensive care clinicians to more safely place a breathing tube or perform other life-saving therapies. ... The microparticles would likely only be administered for a short time, between 15 and 30 minutes, because they are carried in fluid that would overload the blood if used for longer periods ... the particles are different from blood substitutes, which carry oxygen but are not useful when the lungs are unable to oxygenate them. Instead, the microparticles are designed for situations in which the lungs are completely incapacitated. ... Intravenous administration of oxygen gas was tried in the early 1900s, but these attempts failed to oxygenate the blood and often caused dangerous gas embolisms. ... We have engineered around this problem by packaging the gas into small, deformable particles. They dramatically increase the surface area for gas exchange and are able to squeeze through capillaries where free gas would get stuck."

Link: http://www.eurekalert.org/pub_releases/2012-06/chb-ilo_1062212.php

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

This demonstrated technology platform has wide-ranging uses beyond muscular dystrophy. The ability to generate altered versions of a patient's own stem cell populations and then deliver them as needed could be a useful therapy for many conditions: "scientists have turned muscular dystrophy patients' fibroblast cells (common cells found in connective tissue) into stem cells and then differentiated them into muscle precursor cells. The muscle cells were then genetically modified and transplanted into mice. ... In this study, scientists focused on genetically modifying a type of cell called a mesoangioblast, which is derived from blood vessels and has been shown in previous studies to have potential in treating muscular dystrophy. However, the authors found that they could not get a sufficient number of mesoangioblasts from patients with limb-girdle muscular dystrophy because the muscles of the patients were depleted of these cells. Instead, scientists in this study 'reprogrammed' adult cells from patients with limb-girdle muscular dystrophy into stem cells and were able to induce them to differentiate into mesoangioblast-like cells. After these 'progenitor' cells were genetically corrected using a viral vector, they were injected into mice with muscular dystrophy, where they homed-in on damaged muscle fibres. The researchers also showed that when the same muscle progenitor cells were derived from mice the transplanted cells strengthened damaged muscle and enabled the dystrophic mice to run for longer on a treadmill than dystrophic mice that did not receive the cells."

Link: http://www.sciencedaily.com/releases/2012/06/120627142514.htm

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

You might recall a recent Australian study that put forward a correlation between time spent sitting and mortality rate, independent of other factors - i.e. the claim there being that if you sit a lot but exercise moderately then you have a lower life expectancy than if you spent less time in a chair. My thought at the time was that this sort of result ties back into levels of activity:

This is not the first study to propose this correlation, of course. There are a range of others from past years. One has to wonder what the mechanism is here, however - my suspicion is that it actually does all come back down to the level of physical activity in the end. In these massive studies the level of exercise and activity is reported by the participants. A person who stands and works is going to be somewhat more active than a person who sits and works, even though that time may not be categorized as physical activity, or reported differently.

Here is a different study that proposes much the same sort of thing. These researchers - like the authors of another recent study on Alzheimer's disease and activity - used data gathered from worn accelerometer devices rather than the self-reporting of study participants, which in theory should lead to far more confidence in the results.

Association of Sedentary Time with Mortality Independent of Moderate to Vigorous Physical Activity:

Low physical activity levels are a well-known risk factor of mortality. Previous studies have shown that people who do not meet the physical activity recommendations or those who report less moderate to vigorous activity (MVPA) are at increased risk of death. Sedentary behavior has emerged as a potential risk factor independent of MVPA and is defined as engaging in behaviors during the waking day that are done while sitting or reclining and that result in little energy expenditure above rest, such as using the computer, watching television, driving a car, or sitting at a desk.

Recent studies with objectively measured sedentary time data have shown that prolonged time in sedentary behaviors is a cardiometabolic risk factor independent of moderate to vigorous physical activity. Additionally, self-reported sedentary time in several domains including sitting, riding in a car, and TV watching is positively associated with mortality.

...

7-day accelerometry data of 1906 participants aged 50 and over from the U.S. nationally representative National Health and Nutrition Examination Survey (NHANES) 2003-2004 were analyzed. All-cause mortality was assessed from the date of examination through December 31, 2006.

...

This study shows that time spent in sedentary behavior is positively associated with mortality in this representative sample of adults aged 50 and older. Participants in the highest quartile of percentage of time spent sedentary, which corresponds to more than 73.5% of time in men and more than 70.5% in women, had more than 5 times greater risk of death compared to those in the lowest quartile. Importantly, these associations were independent of MVPA.

At some point in the future we won't really have to worry too much about things like this, as medical science will progress to the point at which maintenance of long-term health regardless of lifestyle becomes as much a non-issue as protection from the infectious diseases that plagued our ancestors. But we have a way to go towards that goal, and in the meanwhile it doesn't seem wise to sit back and assume that biotechnology will rescue you from casual negligence. Maybe you'll get lucky, but for those of us in the middle stages of life it looks uncertain indeed. The coming decades are on the cusp between the era of aging as a fact of life and aging as a treatable and reversible medical condition - a lot of deaths will fall on the wrong side of that line, so why not try to shift the odds on whether yours is one of them? Every year gained is big deal in this sort of situation.

The flip side of that coin is, of course, helping to make rejuvenation biotechnology come about more rapidly. If you like being alive and in good shape, it makes sense to work on both (a) common sense health basics like exercise and calorie restriction, and (b) assisting scientific progress. You live in an age in which you can easily accomplish both of these things, thanks to a wealth of health knowledge at your fingertips, and the spread of volunteer, philanthropically funded organizations like SENS Foundation and Methuselah Foundation.

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