Fight Aging!

Take a Look at the New Organ Mprize Site

You folk should take the time to look over the recently launched New Organ Mprize website. It's an attractive initiative of the Methuselah Foundation, and you'll find a fair amount of motivational content there on the subject of growing complex organs for transplant:

Imagine a future where no one has to suffer and die while waiting for an organ that never arrives. New Organ funds that future. With your help, everyone who needs an organ can have one custom made for them from their own cells.

A crowd funded prize to award the team that creates the first complex organ - heart, lung, pancreas, liver, or kidney - from a person's cells.
Banking: Preserve a complex organ for 30 days. Thousands die because the best we can do is less than a day.

Engineering: Build a complex whole organ from a person's cells, transplant it, and have it function for two years.

If you support these goals, then I note that there is currently a matching fund for donations: a pledge drive to raise the first $200,000 by the end of March. They have raised more than $45,000 in pledges this year - so do your part and help! In a world in which a Kickstarter project can pull in a million dollars for an iPhone widget, I'd like to think that it's also possible to rapidly raise a few hundred thousand dollars for a cause that actually matters.

As we walk the road of life, ever more set upon by subtle decay and damage along the way, our health and remaining life expectancy becomes ever more dependent on the state of medical technology. It would be good to wake up twenty years from now knowing that you had made a reasonable contribution in those past decades towards helping ensure your own life and health. When we get to the point in old age at which we need, as a matter of life and death, futuristic tissue engineering and regenerative medicine that can rebuild us from the inside, we'll only have ourselves to blame if it is not yet developed and deployed. The course ahead for the science of human rejuvenation and regeneration is very clear, and whether or not it happens is largely a matter of money and will - how many people are persuaded to work on it, and how greatly are they funded.

So do your part to help! It's not as though you have anything to lose.

β-Amyloid Builds Up in All of Us

Like many age-related conditions, Alzheimer's disease results from an excess in processes of degeneration that are common to all of us. We all have β-amyloid building up in our brains, and we are all being damaged by it (or by the underlying causes that lead to it) - just to a lesser extent. A practical therapy for Alzheimer's that works by removing causes of aggregate buildup is something that everyone would benefit from: "Several lines of evidence suggest that pathologic changes underlying Alzheimer disease (AD) begin years prior to the clinical expression of the disease, underscoring the need for studies of cognitively healthy adults to capture these early changes. The overall goal of the current study was to map the cortical distribution of β-amyloid (Aβ) in a healthy adult lifespan sample (aged 30-89), and to assess the relationship between elevated amyloid and cognitive performance across multiple domains. ... Aβ deposition is distributed differentially across the cortex and progresses at varying rates with age across cortical brain regions. A subset of cognitively normal adults aged 60 and over show markedly elevated deposition, and also had a higher rate of APOE ε4 (38%) than nonelevated adults (19%). Aβ burden was linked to poorer cognitive performance on measures of processing speed, working memory, and reasoning. ... Even in a highly selected lifespan sample of adults, Aβ deposition is apparent in some adults and is influenced by APOE status. Greater amyloid burden was related to deleterious effects on cognition, suggesting that subtle cognitive changes accrue as amyloid progresses."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22302550

Speeding Up the Repair of Broken Bone

News of "fracture putty," an evolution in the use of scaffold material for bone regeneration: recent studies "show promise to significantly shorten the healing time and revolutionize the course of fracture treatment. ... Healing of critical-size defects is a major challenge to the orthopedic research community. Large-bone defects must be stabilized and necessitate technologies that induce rapid bone formation in order to replace the missing tissue and allow the individual to return to rapid function. To date, no single material can suffice. ... In our experiences with large animal models, following the guidelines established by our animal care and use committee, we have been successful in formulating a product that contains mesenchymal stem cells and allows them to survive in the environment of the fracture long enough to elicit the rapid formation of new bone. ... To start the bone regeneration process, the [researchers] used adult stem cells that produce a protein involved in bone healing and generation. They then incorporated them into a gel, combining the healing properties [into] 'fracture putty.' [The] team used a stabilizing device and inserted putty into fractures in rats. Video of the healed animals at two weeks shows the rats running around and standing on their hind legs with no evidence of injury. [The] researchers are testing the material in pigs and sheep, too. ... Our approach is biological with the putty. Other groups are looking at polymers and engineering approaches like implants and replacements which may eventually be combined with our approach. We are looking at other applications, too, using this gel, or putty, to improve spinal fusion outcomes."

Link: http://medicalxpress.com/news/2012-02-uga-discovery-fracture-putty-broken.html

NF-κB and the Insulin Resistance of Aging

There are multiple mechanisms that contribute to the progression of insulin resistance with aging. The most significant contributions seem to stem from excess fat tissue and a sedentary lifestyle, and the metabolic consequences of those choices. (Yes, being fat is absolutely a choice for nearly all people, and one that they could begin to reverse at any point in time by changing the way they live their lives). Avoiding diabetes is a very plausible goal if you keep in shape - but even the most fit of elderly folk suffer some degree of rising insulin resistance and metabolic dysfunction as a consequence of the accumulating biological damage of aging. There is the insulin resistance you can escape, and then there is the insulin resistance you can't.

One line item that crops up when discussing the intersection of exercise, inflammation and insulin resistance, and the course of aging is NF-κB - one of the many machine parts in the cell that seems to have a finger in every pie by virtue of being involved in the process of manufacturing other machine parts. Manipulating NF-κB can extend life in flies, and has beneficial effects in other laboratory animals. Here, a couple of recently published papers look at NF-κB as a regulator of insulin resistance - avoidable and otherwise - and possible target for old-style drug development.

Endothelial NF-κB in Obesity and Aging: Is Endothelial NF-κB a Master Regulator of Inflammation and Insulin Resistance?

Insulin resistance is a major characteristic of type 2 diabetes and develops in multiple organs including skeletal muscle, liver, adipose tissue, and heart. Insulin resistance is caused by obesity and therefore establishes an important causal relationship between obesity and type 2 diabetes. Insulin resistance also develops in aging, but this process is less well understood.

Blockade of the NF-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Lifespans

To examine the role of endothelial NF-κB signaling in vivo, we generated transgenic mice [that] exhibited functional inhibition of NF-κB signaling specifically in endothelial cells. Although [the] mice displayed no overt phenotypic changes when young and lean, they were protected from the development of insulin resistance associated with obesity, whether diet- or genetically-induced.
...

In addition to inhibition of obesity-related metabolic deteriorations, blockade of endothelial NF-κB signaling prevented age-related insulin resistance and vascular senescence and, notably, prolonged lifespan. These anti-aging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity and aortic up-regulations of mitochondrial sirtuin-related proteins. ... Endothelial NF-κB signaling is a potential target for treating the metabolic syndrome as well as for anti-aging strategies.

At the present pace, by the late 2020s researchers will be able to tell you exactly why, how, and how much common lifestyle choices impact your future health and life expectancy. But it's worth noting that this won't help you live any longer - you could make the same smart choices now as you would if presented with a much thicker bundle of scary evidence. The 80/20 of present day widely available health practices is easy to achieve, after all: calorie restriction and regular exercise. None of this, however, gets us any close to true rejuvenation biotechnology. For that, we need more resources heading towards the work of the SENS Foundation and their allies in the research community.

Another Study on Exercise and Telomere Length

If you think that telomere length is a secondary marker of aging and health, then it makes perfect sense that exercise would lengthen telomeres. There is ample evidence to show that average telomere length, while declining with age, is somewhat dynamic in response to circumstances, at least in the white blood cells examined by most present day research: "Leukocyte telomere length (LTL) is a potential indicator of cellular aging; however, its relation to physical activity and sedentary behavior is unclear. The authors examined cross-sectionally associations among activity, sedentary behavior, and LTL among 7,813 women aged 43-70 years in the Nurses' Health Study. Participants self-reported activity by questionnaire in 1988 and 1992 and sedentary behavior in 1992. Telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative polymerase chain reaction. ... For total activity, moderately or highly active women had a 0.07-standard deviation (SD) increase in LTL compared with those least active. Greater moderate- or vigorous-intensity activity was also associated with increased LTL ... Associations remained after adjustment for body mass index. ... Although associations were modest, these findings suggest that even moderate amounts of activity may be associated with longer telomeres, warranting further investigation in large prospective studies."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22302075