Aging is damage: it is the accumulation of broken and obstructed protein machinery and nanoscale structures inside and around our cells. Living beings come with many varied repair systems, so the processes by which damage grows and eventually overwhelms those repair systems is far from straightforward. In that sense aging isn't like the wearing of stone by the weather, or the failure of a non-repairing mechanical system like a car - but it's still all about damage. At the highest level the same mathematical models of damage and component loss that work just fine as aids to understanding failure in complex non-repairing systems like electronics also work just fine for aging.

Every so often a research group feels the need to publicize work in which they damage mice or other laboratory species in ways that cause them to live shorter lives. There are many very subtle ways to alter genes, such as those involved in DNA repair, that produce what is arguably accelerated aging. (Though not everyone thinks that these forms of life span reduction are in fact accelerated aging, but that's a debate for another time and place). The point here is that I think you have to beware of taking it at face value that these research results are relevant to normal aging, or relevant to extending healthy life. You can damage mice with a hammer if you so choose, and it will certainly shorten their life spans, but examining the results won't tell you anything about aging. Similarly, it's the case that near all of the possible ways of interfering in mouse biology via genes and metabolic operation in order to reduce life span are just as irrelevant.

Here is an example of this sort of thing: researchers are producing mice with additional damage in their mitochondria, a component of cellular biology known to be important in all sorts of metabolic processes, and considered to be important in aging, and showing that these mice don't live as long. I don't think that the authors can show that they've proved much of relevance to aging with this study as constructed, however, for the reasons noted above.

Mutations of mitochondrial DNA can hasten offspring's ageing process

In ageing research, mitochondria have been scrutinized by researchers for a long time already. The mitochondria in a cell contain thousand of copies of a circular DNA genome. These encode, for instance, proteins that are important for the enzymes of the respiratory chain. Whereas the DNA within the nucleus comes from both parents, the mitochondrial DNA (mtDNA) only includes maternal genes, as mitochondria are transmitted to offspring via the oocyte and not via sperm cells. As the numerous DNA molecules within a cell's mitochondria mutate independently from each other, normal and damaged mtDNA molecules are passed to the next generation.

To examine which effects mtDNA damage exerts on offspring, researchers used a mouse model. Mice that inherited mutations of mtDNA from their mother not only died quicker compared to those without inherited defects, but also showed premature ageing effects like reduced body mass or a decrease in male's fertility. Moreover, these rodents were prone to heart muscle disease.

As the researchers discovered, mutations of mtDNA not only can accelerate ageing but also impair development: In mice that, in addition to their inherited defects, accumulated mutations of mtDNA during their lifetime, researchers found disturbances of brain development. They conclude that defects of mtDNA that are inherited and those that are acquired later in life add up and finally reach a critical number.

To show relevance, you really need to demonstrate life extension - meaning repair mechanisms for mitochondrial DNA rather than damage mechanisms should be the focus. To shorten life spans through various forms of damage is unlikely to provide anything more than hints and inference when it comes to ways to extend life.

Source:
https://www.fightaging.org/archives/2013/08/damaging-the-biology-of-mice-to-make-them-age-more-rapidly-often-tells-us-little-of-use.php

Long term calorie restriction lowers the risk of cancer in addition to extending life in laboratory animals. Here researchers show that short term calorie restriction appears to augment the effectiveness of treatments for an existing cancer:

While previous studies suggest a connection between caloric intake and the development of cancer, scientific evidence about the effect of caloric intake on the efficacy of cancer treatment has been rather limited to date. When humans and animals consume calories, the body metabolizes food to produce energy and assist in the building of proteins. When fewer calories are consumed, the amount of nutrients available to the body's cells is reduced, slowing the metabolic process and limiting the function of some proteins. These characteristics of calorie restriction have led researchers to hypothesize that reducing caloric intake could potentially help inhibit the overexpression of the protein Mcl-1, an alteration associated with several cancers.

Researchers conducted a series of experiments in mice developing lymphoma resembling Burkitt's lymphoma and diffuse large B-cell lymphoma, two human cancers of the white blood cells. The team began by separating the mice into two categories: those who would receive a regular diet and those who would receive a reduced-calorie diet (75 percent of normal intake) for the duration of the experiment. After the mice consumed either a regular or a reduced-calorie diet for one week, researchers then further divided the mice into four groups according to the treatment they would receive for the following 10 days. Of the two groups of mice that received a normal diet, one (the control group) did not receive treatment and the other received treatment with an experimental targeted therapy, ABT-737, designed to induce cancer cell death. Of the two groups of mice who received a reduced-calorie diet, one did not receive treatment and the other received ABT-737. On day 17 of the experiment, both treatment and calorie restriction ended, and mice had access to as much food as they desired.

Investigators observed that neither treatment with ABT-737 nor calorie restriction alone increased the survival of mice over that of the other mice; however, the combination of ABT-737 and calorie restriction did. Median survival was 30 days in the control group that received a regular diet and no treatment, 33 days in mice that received a regular diet and treatment with ABT-737, 30 days in mice that received a reduced-calorie diet without treatment, and 41 days in mice that received a reduced-calorie diet and treatment with ABT-737. Shortly after this experimental period, investigators also observed that the combination of calorie restriction and ABT-737 reduced the number of circulating lymphoma cells in the mice, suggesting that the combination sensitized the lymphoma cells to treatment.

Link: http://hematology.org/News/2013/10958.aspx

Source:
https://www.fightaging.org/archives/2013/08/calorie-restriction-as-a-means-to-augment-cancer-therapies.php

The British Science Festival will be held in Newcastle a few weeks from now. One of the events has Aubrey de Grey of the SENS Research Foundation, advocate and coordinator for rejuvenation research, debating Tom Kirkwood, one of the leading figures in the mainstream faction of the aging research community who think that there isn't much hope for rapid progress to rejuvenation. Those researchers see the best available path forward as one of modestly slowing aging through replication of known metabolic or genetic alterations associated with natural variations in longevity, such as those involved in the response to calorie restriction - but even this will be a long time in realization, a slow grind towards incremental improvements.

I agree with the viewpoint that attempts to safely slow aging in humans will be very hard indeed. Success requires a much greater understanding of metabolism and aging than presently exists, and it's not unreasonable to suggest that decades and many billions of dollars lie between us and even the first prototype drugs to slightly slow aging. However, slowing aging by altering genes and metabolism is not the only approach that can be taken - indeed it's probably the worst of viable scientific approaches to extending healthy life. It's exceedingly costly, produces marginal results, and therapies that can slow ongoing aging are of little to no use for people who are already old and frail.

In this Kirkwood represents the old mainstream of standardized drug discovery and marginal, unambitious process in medicine. De Grey represents the disruptive future of medical technology, his SENS vision and ongoing research being one of a number of entirely new paradigms for health and aging that are winning over an increasing fraction of the research community. The times are changing, and every new wave of development is met by skepticism from those in the mature industries it will replace. We should aim for rejuvenation through periodic repair of cellular damage: it will like take no longer, will quite possibly be cheaper than trying alter ourselves to slow aging, and will be very beneficial for people who are already old when these therapies are introduced.

Life Without Ageing - Two Contrasting Visions Of An Ageing World

EVENT: Life Without Ageing - Two contrasting visions of an ageing world
DATE: Monday 9th September TIME: 13.00 - 14.30
VENUE: Fine Art Building Lecture Theatre, Newcastle, UK

Is a cure for ageing within reach in our own lifetimes?

Biomedical gerontologist Dr Aubrey de Grey, Chief Science Officer of the SENS Research Foundation will be joining Professor Tom Kirkwood CBE, Associate Dean for Ageing at Newcastle University to debate a 'Life Without Ageing'. In this event, chaired by Dr Sir Tom Shakespeare, Aubrey de Grey will suggest that a "cure" for ageing is within reach in our own lifetimes, while Tom Kirkwood will argue that such a goal is not only unrealistic but distorts what should be the real research priorities of an ageing world.

Dr de Grey's research proposes that eliminating ageing as a cause of debilitation and death in mankind can be achieved within just a few decades through his proposed 'Strategies for Engineered Negligible Senescence'; a term coined by De Grey in his first book The Mitochondrial Free Radical Theory. Countering this is Professor Kirkwood, a former BBC Reith Lecturer, whose research is around healthy ageing and improving life in old age by looking at the prevention of age associated factors, such as frailty, disability and age related disease, and by helping to change society's attitudes towards ageing.

The tantalising idea of living forever is as old as humanity, but can modern science really hope to consign the ageing process to history? Life Without Ageing promises to be a fascinating insight into modern day ageing research and the opposing visions of an ageing world. At the end of the debate the floor will be opened, giving the audience opportunity to put questions to the speakers and take part in what should be a lively discussion.

If you take a careful look at the festival site page for the debate, you'll see that it's possible to submit questions for the speakers. If you intend to go in person, it looks like registration is required, but it's otherwise a free event.

Source:
https://www.fightaging.org/archives/2013/08/life-without-ageing-aubrey-de-grey-and-tom-kirkwood-to-debate-longevity-science-at-the-british-science-festival.php

Technologies derived from rapid prototyping and 3-D printing will likely play an important role in the future of tissue engineering, just as they are coming to do in many fields:

The field of tissue engineering has deployed several fabrication strategies aimed at bringing cells and structure together to generate tissue. Biomaterial scaffolding - which provides structural support and can be formed into biologically relevant shapes - has been combined with cells to generate hybrid 3-D structures for use as tissue surrogates in vitro and in vivo. Protocols have been developed that enable removal of living cells from native tissues, leaving only a natural scaffolding of extracellular matrix, which can then be re-seeded with cells to reconstruct or partially reconstruct 3-D tissues. Another approach to soft tissue reconstruction has been the development of cell-laden hydrogels, which are often cast into a specific shape and placed into a permissive environment in vitro or in vivo that allows maturation and establishment of tissue-specific characteristics. In recent years, with the advancement of 3-D printing technologies for the on-demand fabrication of complex polymer-based objects, efforts have been underway to adapt 3-D printing technologies and engineer bioprinting instruments that can leverage similar 3-D replication concepts and accommodate the incorporation of living cells.

Organovo's NovoGen MMX Bioprinter precisely dispenses "bio-ink" - tiny building blocks composed of living cells - generating tissues layer-by-layer according to user-defined designs. Built for flexibility, the bioprinter enables fabrication of tissues with a wide array of cellular compositions and geometries; side-by-side comparison of multiple tissue prototypes facilitates optimization and selection of specific designs geared toward a particular application. Working within the confines of an object library, bio-ink building blocks of various shapes, sizes and compositions are assembled into architectures that recapitulate the form of native tissue. Tubes, layered sheets and patterned structures have been bioprinted, yielding 3-D tissues that are free of biomaterial scaffolding and characterized by tissue-like microarchitecture, including the development of intercellular junctions and endothelial networks.

In the short-term, 3-D human tissues are being deployed in the laboratory setting as models of human physiology and pathology; cell-based assays are a mainstay of the drug discovery and development process, and multicellular/multitissue systems may serve as more predictive indicators of clinical outcomes. Longer-term applications of 3-D tissue technologies will extend our knowledge of how to build the smallest functional units of a tissue to the fabrication of larger-scale tissues useful for surgical grafts to repair or replace damaged tissues and organs in the body. What are the next steps in the evolution of bioprinting? The first step is scaling up and down - increasing the resolution of specific features while advancing fabrication hardware and techniques to produce larger-scale tissues. The next, enhancing the complexity of designs - building the tool set that enables conceptual or visual inputs to be translated rapidly to executable bioprinting programs that select from a library of bio-ink building blocks to translate the vision into reality.

Link: http://www.rdmag.com/articles/2013/08/3-d-printing-life-science-applications

Source:
https://www.fightaging.org/archives/2013/08/a-short-overview-of-3-d-printing-in-tissue-engineering.php