There should be no such thing as "I don't know what to do with my life." Scratch that statement away and erase it, as it should be "I will aid the development of life extension technology until I do know."

It should be no surprise to anyone that many, or perhaps even a majority of people at any given time have no real idea as to what they want to do with their lives. No vision, no grand dream that captures them, no burning desire to achieve a specific great work. That isn't because they are incapable - far from it, it is because they haven't found their own personal blue touch paper yet. The space of ideas and ideals is vast, and even the most aggressively autodidactic internet-addicted polymath cannot embrace more than a fraction of the sphere of human knowledge. Yet you cannot know your grand vision, the one that resonates with everything your life has led to up until that point, if you never encounter its roots.

Which is where we come back to time. We tell the younger folk that it doesn't matter if they don't know what they want to do with their lives, as that knowledge will come with time. The rituals and mythology that spring from the passage from childhood to adulthood, repeated billions of times over the course of history, are as much about expanding horizons as they are about anything else. In our comparatively wealthy modern society, that process of expansion doesn't have to stop when you stop growing in body - except for the fact that we are all limited by the realities of the human condition, and aging in particular.

Our lives have a timer, and we are all well aware of it, for all that many of us prefer not to think about it at all. The whole structure of life and society revolves around the existence of that timer, as it ticks away the freedom we have remaining in which to find and work on something worthwhile. The rush to find meaning in life? There because we don't have enough time. The need to save for retirement and medical costs? The timer again, ticking away our health and ability to fend for ourselves.

When you cannot see even the first shape of what will be your life's work, and time is ticking away, the best thing you can do is to offer a helping hand to those who work on making more time - scientists, advocates, and others who support research and development of rejuvenation biotechnologies. You can do that at the same time as you search for the cause or idea that truly speaks to you, and it beats slumping back into the grey doldrums that seem to afflict so much of our society: people who never found that fire inside, and who have no time left in which to do so.

You have an option that the older folk of previous generations did not: you can help make more time for everyone, more health, more years, and time enough to find meaning in what you do.

Artificial cells are one possible line of future biotechnology; devices built to resemble the body's building blocks, essentially nanomachines constructed of proteins. Here researchers take a modest step in that direction, by developing "a novel method of disguising nanoparticles as red blood cells, which will enable them to evade the body's immune system and deliver cancer-fighting drugs straight to a tumor. ... The method involves collecting the membrane from a red blood cell and wrapping it like a powerful camouflaging cloak around a biodegradable polymer nanoparticle stuffed with a cocktail of small molecule drugs. Nanoparticles are less than 100 nanometers in size, about the same size as a virus. ... This is the first work that combines the natural cell membrane with a synthetic nanoparticle for drug delivery applications. This nanoparticle platform will have little risk of immune response. ... Stealth nanoparticles are already used successfully in clinical cancer treatment to deliver chemotherapy drugs. They are coated in a synthetic material such as polyethylene glycol that creates a protection layer to suppress the immune system so that the nanoparticle has time to deliver its payload. ... today's stealth nanoparticle drug delivery vehicles can circulate in the body for hours compared to the minutes a nanoparticle might survive without this special coating. But in [this latest] study, nanoparticles coated in the membranes of red blood cells circulated in the bodies of lab mice for nearly two days. ... one of the next steps is to develop an approach for large-scale manufacturing of these biomimetic nanoparticles for clinical use. ... Researchers will also add a targeting molecule to the membrane that will enable the particle to seek and bind to cancer cells, and integrate the team's technology for loading drugs into the nanoparticle core so that multiple drugs can be delivered at the same time."

Link: http://www.sciencedaily.com/releases/2011/06/110620161300.htm

From the Technology Review: "The drug rapamycin has been found to reverse the effects of Hutchinson-Gilford progeria syndrome, a fatal genetic disease that resembles rapid aging, in cells taken from patients with the disease. Rapamycin, an immunosuppressant drug used to prevent rejection of transplanted organs, has already been shown to extend life span in healthy mice. Researchers hope the findings will provide new insight into treating progeria as well as other age-related diseases. Skin cells from patients with progeria show a slew of defects: deformities in their membranes, decreased growth, and early death. [Researchers] found that rapamycin could reverse these defects by enhancing the cells' ability to degrade the protein progerin, which accumulates in abnormal amounts in progeria patients. It's not yet clear whether the drug will have similar effects on animals or patients. But progeria researchers are planning a clinical trial of rapamycin. ... Researchers say the findings could be relevant beyond this rare genetic disease. Although accumulation of progerin is associated with progeria, the protein also accumulates in small amounts in normal cells, and may be partially responsible for the aging process."

Link: http://www.technologyreview.com/biomedicine/37916/

As you may know, a range of ways to extend life in nematode worms (such as the common laboratory species Caenorhabditis elegans) involve interfering in the operation of mitochondria. This is also true in a range of other lower animals - mitochondrial operation is apparently strongly coupled to the natural range of longevity enjoyed by a given species. But what are mitochondria? They are a roving swarm of tiny power plants, present inside every cell, and inside each mitochondrion there can be found an array of intricate molecular machinery that gives rise to what is called the electron transport chain. This is a critical component in the process of building stores of chemical energy - in the form of ATP - used to power the operation of the cell. It is alterations in the operation of the electron transport chain that can alter longevity for the better in many species.

A recent open access paper digs into other mechanisms that relate to this link between electron transport chain operation and life span, outlining the discovery of a gene that is necessary for that enhanced longevity:

Mitochondria have long been associated with aging and age-related diseases. Recent research has shown that a slight dampening of mitochondrial function can dramatically increase the lifespan of a wide range of organisms, suggesting that a similar mechanism likely operates in humans. The molecular basis of this observation is largely unknown, however. Uncovering the genes that allow altered mitochondrial function to impact longevity will give us important new insights into how mitochondria affect the aging process and will pave the way for future therapeutic developments aiming to improve healthy aging and to treat age-related diseases.

Here, we used an RNAi screen in the genetic model organism C. elegans, a nematode worm, to uncover how altered mitochondrial function can modulate longevity. We found that in order for mitochondria to affect lifespan, they must communicate with several unique transcription factors in the nucleus. Notably, we discovered that the putative homeobox transcription factor CEH-23, which has not previously been implicated in longevity determination, is able to respond to changes in mitochondrial function and in turn causes an extension in lifespan. ... ceh-23 expression levels are responsive to altered METC, and enforced overexpression of ceh-23 is sufficient to extend lifespan in wild-type background.

So it looks like some form of programmed response causes the life extension in these methods, and manipulations of the electron transport chain only trigger that response - which is interesting. Not what you might expect, given all the other ways in which mitochondria touch on aging, such as through accumulated damage to their DNA.

A long and fascinating post from Chronosphere details the extensive preparations that go into transporting the body of a cryonics patient for cryopreservation: "Many patients will be remote from the facility where cryoprotective perfusion will be carried out and will be transported by common carrier or private carrier over considerable geographical distances. In some cases it will be possible to move the patient using a specialized transport vehicle with on-going extracorporeal support. In other cases the distances will be sufficiently great that the only realistic option is iced-shipment in the absence of perfusion. It is often necessary to use a commercial air freight service to move the patient from one area of the United States to another (or from one country to another). ... Because of time constraints to get freight loaded rapidly, air freight is often not handled with care by airport personnel. ... Whenever possible, the Transport Technician should supervise the handling of the patient every step of the way, including on and off the aircraft. Due to recent terrorist acts it has become increasingly difficult for the Transport Technician to do this. Until quite recently it was usually easy for the Technician to get access to air freight facilities and the tarmac to supervise loading of the patient onto the aircraft. This is now all but impossible. However, it is still important to accompany the patient to the air freight depot and to emphasize that extra care should be used in handling the patient, and that every precaution should be taken against misrouting."

Link: http://chronopause.com/index.php/2011/06/28/commercial-air-transport-of-the-cryopreservation-patient/

You may recall that composition of cell membranes is strongly correlated to species longevity - the idea being that some membranes are more resistant to the damage of reactive oxygen species than others, and that damage resistance at the cellular level ultimately translates into a longer-lived animal. Here is more on that topic: "This review begins with the premise that an organism's life span is determined by the balance between two countervailing forces: (i) the sum of destabilizing effects and (ii) the sum of protective longevity-assurance processes. Against this backdrop, the role of electrophiles is discussed, both as destabilizing factors and as signals that induce protective responses. Because most biological macromolecules contain nucleophilic centers, electrophiles are particularly reactive and toxic in a biological context. The majority of cellular electrophiles are generated from polyunsaturated fatty acids by a peroxidation chain reaction that is readily triggered by oxygen-centered radicals, but propagates without further input of reactive oxygen species(ROS). Thus, the formation of lipid-derived electrophiles such as 4-hydroxynon-2-enal (4-HNE) is proposed to be relatively insensitive to the level of initiating ROS, but to depend mainly on the availability of peroxidation-susceptible fatty acids. This is consistent with numerous observations that life span is inversely correlated with membrane peroxidizability and with the hypothesis that 4-HNE may constitute the mechanistic link between high susceptibility of membrane lipids to peroxidation and shortened life span. Experimental interventions that directly alter membrane composition (and thus their peroxidizability) or modulate 4-HNE levels have the expected effects on life span, establishing that the connection is not only correlative but causal. Specific molecular mechanisms are considered, by which 4-HNE could (i) destabilize biological systems via nontargeted reactions with cellular macromolecules and (ii) modulate signaling pathways that control longevity-assurance mechanisms."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21708248

Type 2 diabetes is the poster child for an avoidable age-related condition: barring the worst of genetic bad luck, calorie restricted, well exercised people will not suffer from type 2 diabetes. But this is, undeniably, an age-related illness. Becoming ever more obese and sedentary will hasten the onset of diabetes into ever earlier years of life, but older obese and sedentary people are still far more likely to suffer type 2 diabetes than are equally overweight and sedentary younger counterparts. So while failing to take care of your health at any age is just another form of self-harm, there are other, less avoidable processes taking place at the level of cells and organs that make older people more vulnerable.

Here is an open access paper that reviews what researchers presently know of the decline of insulin-producing beta cells in the pancreas - which turns out to be not enough, as is still true of so much of our biochemistry. There are changes, cataloged and identified, but the chains of causation for those changes are poorly understood at best.

Type 2 Diabetes and the Aging Pancreatic Beta Cell

An increased incidence of diabetes is observed with age, and there are many possibly reasons for this. One of these is that the beta cell has reduced proliferative capacity and in diabetic individuals this is further confounded by higher rates of beta cell apoptosis. The currently known underlying mechanisms behind the reduction in beta cell proliferation observed with age include reduced expression of cell cycle activators, increased expression of cell cycle inhibitors, reduced pdx1 expression, and increased amylin aggregation. Studying aging in the non-diabetic rodent and human models is currently a developing field; therefore very few broad conclusions can be drawn. Further study in these areas is important as they could indicate targets for preventing or slowing the progression of diabetes with age.

I look on this as a good illustration of why the detailed, tissue by tissue, understand everything approach to repairing aging is doomed to take a very long time indeed. This is but one population of vital cells in one organ, one of the most studied forms of cell in past decades, and the research community remains far from a complete understanding as to how and why they fail with age.

Better strategies to deal with aging exist - such as SENS - and need to gain wider support and adoption. SENS-like approaches work around the challenge posed by the sheer complexity of human biochemistry by focusing on the known common mechanisms of aging, the root causes from which there is good reason to believe all other changes descend. Repairing these root causes is the fast path to the first generation of rejuvenation biotechnology, and that, in my eyes, is the only real shot at building viable interventions in the aging process that will arrive in time to help us.

I'm pleased to see that the Immortality Institute / Longecity has completed fundraising for their latest project, an investigation of the potential benefits of microglia transplants in the aging brain:

After months of fundraising we are now delighted to announce that the project has started! Through many donations large and small, the community has raised sufficient funds to initiate the project. Last month, we passed the 80% mark and knew that full success would only be a matter of time. Then, something amazing happened: though promoting this effort, a far sighted investor has stepped forward who can see the potential in developing this research project. The angel [committed] a substantial contribution towards a research arm that is closely aligned to the project LongeCity is funding. Thus, we have achieved something amazing together: every dollar donated to this life extension research project has not only been doubled through internal funds but multiplied manifold! Few people, especially those with very limited personal means, who want to invest in life extension would find such effective opportunities to make a real difference.

Which is good news all round. I've mentioned this effort in past months, so you can head on back into the archives for more details on the funded research. We live in an age in which a large range of meaningful early-stage work in biotechnology can be performed for comparatively little money - a few tens of thousands of dollars, or less. A single young researcher with lab access can validate theories, determine whether a line of research has promise, or make new connections in a field - and all in a matter of a few months to half a year of work, as one of a number of ongoing projects.

Most importantly, the new reality of low costs means that people of everyday means can band together in small associations to fund the research that they find important, on a project by project basis. This sort of grassroots, bottom-up organization is greatly aided by the internet, but crowdsourced philanthropy for science in detail is only just in its infancy. Projects like those undertaken by the Immortality Institute volunteers are the first signs of the true future of research funding - a detailed and glorious patchwork in which everyone can pick and choose the exact projects they wish to fund, and in doing so learn more about the science behind the causes they support.

Another sign of progress in this direction is the creation of dedicated crowdsourced scientific philanthropy initiatives like FundScience, which has actually been around for a couple of years, and will be holding a meetup on July 15th in the Bay Area:

FundScience was formed to get the public invested in science. We aim to accomplish two goals:

1. Provide a way for scientists and researchers to self fund their research by crowd funding.

2. Bring people closer to science by providing an insight into research activities done across the globe.

In addition to staying in touch with scientific activity via FundScience.org , we are launching monthly meetups to give you an opportunity to get to know your favorite researchers in person. Come find out how you can be a part of their amazing work.

I co-founded FundScience a few years ago with the hope of getting the public invested in science. We had two goals when we began. The first was to get much needed funding and guidance to young researchers. The other was to get non-scientists to interact with researchers and understand the research process. Our first round of projects was selected and posted on the site late last year. In keeping with our goal of bringing science to the masses we've decided to complement our online presence with a monthly meetup were we can get researchers to discuss their advancements and get non-scientists to come and ask questions, interact and fund some projects.

There are a fair number of philanthropic ventures that help funnel dollars from many donors to worthy causes, such as Philanthroper for example, but still very few ventures that take the next step of breaking things down into fine-grained projects. Much of the wall between the broader charitable public and the details of the work they support is, I feel, unnecessary. The faster it evaporates the better off we'll all be.