Category Archives: Longevity Medicine

A little while back, I was invited to preview an independent project under development at the behest of Alex Zhavoronkov, one of the trustees of the UK-based Biogerontology Research Foundation, a group with strong ties to the Methuselah Foundation and SENS Foundation communities. That project is now launched and open to the world: it is the International Aging Research Portfolio - "tracking international progress in aging research".

The site grants users access to research and funding information for over a million [projects]. The IARP is a fully searchable, flexible and highly scalable knowledge-management system developed to enable organizations to collaborate, track, analyze, structure, make decisions and set directions for future research efforts in aging. ... Aging research spans many areas of natural and social and behavioural sciences and requires a high degree of interdisciplinary and international cooperation. The goal of IARP is to provide a centralized decision support system for scientists, research institutes, funding organizations and policy makers involved in aging research.

If you are a statistics addict, this might keep you occupied for a while. The aggregated funding data and trends in research are particularly interesting, and could be more so if further sliced and diced. For example, funding by theory of aging:

Color me surprised that funding of work on telomeres in aging is so very far ahead - but there's the purpose of data mining, to learn. The hope here is that data mining tools that operate on this large data set will provide compelling benefits for the research community, such as by making it easier to match up research proposals to funding sources based on the sort of awards made in the past.

Public sources of funds are over-represented in this database by virtue of being public sources and thus producing records that are generally more accessible. One can imagine a slow extension of such a data aggregation operation into the private funding space based on the same provision of compelling benefits. If you make it worthwhile by streamlining the process of fundraising (on the research side) and the process of finding suitable projects to fund (on the funding source side), then people will use the system and in the process support its evolution and growth.

We expect to see good correlations between many aspects of our biology and aging: "Epigenetic variations have been widely described to occur during the aging process. To verify if these modifications are correlated with the inter-individual phenotypic variability of elderly people, we searched for a correlation between global DNA methylation levels and frailty. We found that the global DNA methylation levels were correlated to the frailty status in middle/advanced-aged subjects but not with age. A 7-year follow-up study also revealed that a worsening in the frailty status was associated to a significant decrease in the global DNA methylation levels. These results suggest that the relaxation of the epigenetic control in aging is specifically associated with the functional decline rather than with the chronological age of individuals. Thus, the modifications of DNA methylation, representing a drawbridge between the genetic and the environmental factors affecting the age-related decay of the organism, may play an important role in determining physiological changes over old age." Equally, it may go the other way - these changes could just as well be the symptoms of damaged systems flailing as they try to adapt to countless small breakages at the level of cells and molecular machinery. It is important in the development of therapies for aging to try to identify the root causes, as fixing those will also solve secondary issues.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21336567

Decellularization is proving to be a versatile technology in tissue engineering: grow the tissue from stem cells or accept a donor organ, strip its cells to leave behind the extracellular matrix, and then repopulate it from the recipient's stem cells to make it ready for transplant. For example: "Heart bypass patients may soon be able to get new arteries without having to sacrifice vessels from other parts of their body, thanks to ready-made, off-the-shelf artificial blood vessels. Biomedical engineers have been trying to build replacement blood vessels, needed for coronary artery bypass surgery and kidney dialysis patients, for three decades. Researchers from Humacyte Inc., in Durham, N.C., discovered the trick: recruiting cells to build the vessel, then washing them away so the nonliving tissue is storable and works for anyone. ... The company has managed to make a "universal blood vessel. This is very practical and convenient for clinical applications. ... Other approaches, customized with a patient's own cells, take several months to prepare. ... Though Humacyte is starting to plan human clinical trials, it's too early to predict when the grafts would become available to the general public. ... [researchers] not yet know how much the grafts would cost, but anticipates it will be less than the $15,000-and-up for personalized grafts from patient's own cells. The company can use cells from multiple cadavers to generate hundreds of grafts at once, making production much cheaper."

Link: http://www.latimes.com/health/la-he-blood-vessels-20110221,0,6930611.story

I am not complacent about the cancers that no doubt lie in my future - just as they lie in yours. But I am not terribly concerned either; I give more thought to the fate of my wallet than to the fate of my flesh when it comes to cancer. By the time I hit the stage of life at which cancers are most likely to manifest, then the state of the art in safe and robustly effective cancer therapies will be impressive indeed. That will be true even if all that happens in between now and then is that the present technology demonstrations carried out in laboratories are developed into commercially available therapies ... and I'd expect far more progress than that to happen over a twenty year span of time.

Here are two more reassuring examples of ongoing development in biotechnology for those of us fortunately enough to have the luxury of time when it comes to cancer - even if we certainly don't have the luxury of time when it comes to aging itself.

Nanotechnology may lead to new treatment of liver cancer:

Researchers evaluated the use of molecular-sized bubbles filled with C6-ceramide, called cerasomes, as an anti-cancer agent. Ceramide is a lipid molecule naturally present in the cell's plasma membrane and controls cell functions, including cell aging, or senescence. ... The beauty of ceramide is that it is non-toxic to normal cells, putting them to sleep, while selectively killing cancer cells

...

Cerasomes [can] target cancer cells very specifically and accurately, rather than affecting a larger area that includes healthy cells. The problem with ceramide is that as a lipid, it cannot be delivered effectively as a drug. To solve this limitation, the researchers use nanotechnology, creating the tiny cerasome, to turn the insoluble lipid into a soluble treatment.

...

Researchers [previously] observed that cerasome use led to complete remission in aggressive, large granular lymphocytic leukemia in rats. ... It is plausible that preventing liver tumor vascularization with cerasome treatment could induce widespread apoptosis, a genetically programmed series of events that leads to cell death in tumors

The Answer To Wiping Out Cancer Could Be World's First Chemical Guided Missile:

Current cancer treatments destroy the cells that form the bulk of the tumour, but are largely ineffective against the root of the cancer, the cancer stem cells. This suggests that in order to provide a cure for cancer we must accurately detect and eliminate the cancer stem cells.

...

researchers have [created a targeted] RNA aptamer, a chemical antibody that acts like a guided missile to seek out and bind only to cancer stem cells. The aptamer has the potential to deliver drugs directly to the stem cells (the root of cancer cells) and also to be used to develop a more effective cancer imaging system for early detection of the disease.

Many different research groups are developing many different competing methods of both targeting cancer cells and delivering existing chemotherapy compounds in a highly targeted way. The chemical compounds used in many existing cancer therapies could be the basis for very safe and very effective future therapies if only they could be delivered just to cancer cells, and in small doses that did not leak out into neighboring tissues. This is exactly the capability being demonstrated over the past few years in laboratories around the world.

Researchers demonstrate that exercise can counter some of the effects of an engineered acceleration of mitochondrial dysfunction: "researchers [found] that signs of premature aging were halted - and even reversed - in virtually every tissue and organ in the bodies of exercised mice. Mice genetically altered to age faster were forced to run on treadmills for 45 minutes, three times a week. Five months later, the mice looked as young, healthy and active as wild-type mice - mice that didn't have the genetic mutation - while their sedentary and same-aged siblings were balding, greying and shrinking. .. The mice were genetically manipulated to age twice as fast as normal because of a defect in the repair system of their mitochondria, the powerhouses or furnaces inside each cell that give our body energy. Evidence has been mounting for decades that the older we get, the more mutations we accumulate in mitochondrial DNA. The furnaces start to break down, resulting in a steady decline in tissue and organ function. ... In our study, we saw huge recovery in mitochondrial function [in] the exercised mice." We might expect this result, given that exercise is known to have an impact on longevity, as well as on many of the biological mechanisms that are associated with aging. Given the importance of mitochondria in aging, it is interesting to see more work on the links between exercise and their function - but we must always be careful when evaluating work based on engineered dysfunction or accelerated aging. It is often the case that the putative end result has little relevance to "normal" aging.

Link: http://www.vancouversun.com/health/health/4321105/story.html

An open access paper: "Nearly 50 years ago geneticist James Neel famously proposed that 'thrifty genes' were important contributors to the rising prevalence of diabetes. Such genes promote efficient use and conservation of food energy, he theorized, and thus were favored by natural selection to help our ancient ancestors cope with famines. Now widespread in various populations, they predispose to obesity and diabetes, abetting a tendency to prepare for famines that never come. ... Here I propose an extension of this reproduction-centered version of Neel's theory that bears on aging. One of my key premises is that many windows of opportunity for reproductive booms occurred during the Holocene as agricultural innovations spread, periodically increasing food availability between times of nutritional stress. The periods of plenty selected for genotypes capable of rapidly ramping up fecundity as food intake increased. ... I believe the boom times' selection of genotypes prone to nutrition-cued accelerated development is having an especially problematic effect today because of widespread childhood overnutrition. Accelerated development, which enhanced reproductive success in the past, now has a pro-aging effect with rapidly growing costs. Indeed, when viewed through the lens of the antagonistic pleiotropy theory of aging, this effect seems anything but thrifty: It predisposes toward what might be called the spendthrift phenotype, characterized by chronic activation of pro-growth pathways - notably those involving mTOR, insulin, and insulin-like growth factor-1 - that support rapid development and sexual maturation but that also underlie later senescence. The modern fallout encompasses a much broader array of age-associated ills than the diabetes that prompted Neel's original hypothesis. Indeed, the spendthrift phenotype may well increase the age-associated risks of most if not all diseases of aging, like the ruinous adult legacy of flush, fast-living youth."

Link: http://www.impactaging.com/papers/v3/n2/full/100286.html