Longevity News

Graveyard Dirt May Tell Us How to Live Longer

posted on August 10, 2010

Scientists are searching graveyards for clues to longevity. Ironic but true. They’re looking for new enzymes to clean up old cells.

Our metabolisms generate a small but steadily growing amount of waste chemicals that cannot be broken down in the body. This junk accumulates in the recycling mechanism called the lysosome. Lysosomes are like garbage disposals of the cells. They contain enzymes that break up cellular debris. The accumulated junk is especially problematic in long-lived cell populations, like those that exist in the nervous system and brain. Recycling breaks down, and the cells malfunction, causing more damage elsewhere, or die. What can we do about this?

Reason, in www.FightAging.org, elaborates how cells have a lot of reasons to break down big molecules and structures into their component parts, and a lot of ways to do so. Unfortunately, one of the main reasons to break things down is because they have been chemically modified so that they no longer work, and sometimes these chemical modifications create structures so weird that none of the cell's degradation machinery works on them. This situation is very rare, but in the long run these modified chemicals add up.

Ultimately the chemicals end up in the lysosomes. These special vessels contain the most powerful degradation machinery in the cell. If something can't be broken down there, it just stays there forever. This doesn't matter much in cells that divide regularly, because division dilutes the junk enough that it remains at harmlessly low levels. But non-dividing cells gradually fill up with this stuff, making them dysfunctional. The heart, brain, the back of the eye, some nerve cells (especially motor neurons) and, most of all, white blood cells trapped within the artery walls all suffer from this.

Medical bioremediation is the name given to the SENS Foundation’s approach to removing one class of harmful waste chemicals that accumulate in our cells with advancing age. The development of therapies of biomedical remediation breaks down into two distinct lines of research: First, they identify naturally occurring bacterial enzymes that digest these unwanted junk chemicals. We know bacteria containing these enzymes exist, because we find no remnants of this chemical junk in graveyards, battlefields, slaughterhouse grounds, and so forth. The SENS Foundation funds a program aimed at discovering enzymes that will be safe to introduce into the human body, and they have achieved some degree of success in recent years.

The second theme in biomedical remediation research is delivering suitable enzymes where they are needed: the lysosomes within our cells. Fortunately, this is an area where researchers are already hard at work. Delivering the correct enzymes to a patient's lysosomes are applicable to biomedical remediation aimed at rejuvenating the malfunctioning, clogged-up lysosomes of the elderly.

It never ceases to amaze me how creative people can be when millions of lives are on the line. Searching graveyards for clues to life is really thinking outside the coffin… oops, I mean outside the box.

Long Life,
David Kekich

P.S. Brussels is supposed to be beautiful in October. There’s a special reason to plan a trip there this October if you have an interest in networking with fellow life extensionists and seeing some of the world’s leading researchers and other personalities speak. For details, go to http://www.imminst2010.com/.
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LATEST HEALTHY LIFE EXTENSION HEADLINES

REPROGRAMMING CELLS FOR HEART REGENERATION (August 06 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4845
From the Telegraph: "In as little as five years, researchers hope to be able to coax the heart into regenerating itself, repairing the damage caused by cardiac arrests and old age. It works in a similar way to stem cells but instead of the new cells being grown outside the body and then injected back in, the technique simply makes the cells [transform] at the point where they are needed. The main problem is that when beating muscles cells - known as cardiomyocytes - die during an attack there is no way to reactivate them and the surrounding connective tissue - known as fibroblasts - cannot take over their role. Now [researchers] have discovered a way of reprogramming fibroblasts into cardiomyocytes. We first have to test if the same factors can convert human fibroblasts to beating heart muscle and then find ways to safely introduce these factors, or small molecules that mimic these factors, into the coronary circulation so they can reprogram the existing fibroblasts in the heart. I envision such factors being loaded into a stent that is placed in the coronary artery and can elute (allow to emerge) the reprogramming factors over 1-2 weeks. The team found that they needed a combination of just three substance - Gata4, Mef2c, and Tbx5 - to efficiently convert fibroblasts into cells that could beat like cardiomyocytes."

EMBRYONIC AND INDUCED PLURIPOTENT STEM CELLS IDENTICAL? (August 06 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4844
These researchers argue that embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are most likely the same in any aspect that matters: "the pluripotency of ES cells fueled excitement over their use in regenerative medicine. While ethical hurdles associated with the clinical application of human ES cells appeared to have been overcome with the development of methods to create iPS cells, some recent research has suggested that ES and iPS cells have substantial differences in which sets of genes they express. These findings [argue] to the contrary, rekindling hopes that, under the proper circumstances, iPS cells may indeed hold the clinical promise ascribed to them earlier. iPS cells are made by introducing three key genes into adult cells. These reprogramming factors push the cells from a mature state to a more flexible embryonic stem cell-like state. Like ES cells, iPS cells can then, in theory, be coaxed to mature into almost any type of cell in the body. Unlike ES cells, iPS cells taken from a patient are not likely to be rejected by that patient's immune system. This difference overcomes a major hurdle in regenerative medicine. At this stage, we can't yet prove that they are absolutely identical, but the available technology doesn't reveal differences. Some earlier studies have indicated that iPS and ES cells are dissimilar enough to be classified as different cell types. [The researchers] concluded that the differences noted in other studies were not consistent between different laboratories and thus were not likely to be a result of fundamental differences between the cell types."

A LYSOSENS UPDATE (August 05 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4843
LysoSENS is a project of the SENS Foundation aimed at developing a means to safely remove harmful metabolic byproducts (such as 7KC) that accumulate in lysosomes with age. That buildup degrades the lysosomal ability to clear cells of unwanted junk, which in turn leads to what is known as the garbage catastrophe in aging. At the moment, LysoSENS work focuses on discovering bacterial enzymes that can break down the most important forms of unwanted junk in the lysosome. Here is a progress report from one of the researchers: "The 7KC-degrading bacterium I've been studying, Rhodococcus jostii RHA1, has two large gene clusters that are up-regulated by 7KC, but not cholesterol. In these two gene clusters lie a number of enzymes we believe are involved in 7KC degradation, including an enzyme that could reduce the 7-keto group to a hydroxyl. What makes this interesting to us is that while 7KC is highly cytotoxic, 7alpha-hydroxycholesterol (7alphaOH) is relatively harmless. So I am now methodically going through suspected candidates, searching for reductase activity against 7KC. Currently I am looking at nine different enzymes, and am in various stages of cloning the genes into expression vectors and assaying their products for activity. While I've uncovered some interesting findings, so far I haven’t found the reductase I'm looking for. This could be for several reasons, the first being that I haven't assayed all the enzymes I need to. As I still have the majority remaining, this is a likely scenario. However, one possibility is that the normal substrate for the enzyme is not 7KC, but some downstream metabolite."

CALORIE RESTRICTION PRESERVES NERVE-MUSCLE CONNECTIONS (August 03 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4839
Via KurzweilAI: "researchers have uncovered a mechanism through which caloric restriction and exercise delay some of the debilitating effects of aging by rejuvenating the connections between nerves and the muscles that they control. Their research, conducted through laboratory mice genetically engineered so their nerve cells glow in fluorescent colors, shows that some of the debilitation of aging is caused by the deterioration of connections that nerves make with the muscles they control, structures called neuromuscular junctions. These microscopic links are remarkably similar to the synapses that connect neurons to form information-processing circuits in the brain. The work showed that mice on a restricted-calorie diet largely avoid that age-related deterioration of their neuromuscular junctions, while those on a one-month exercise regimen when already elderly partially reverse the damage. With calorie restriction, we saw reversal of all of these things. With exercise, we saw a reversal of most, but not all. ... Because of the study's structure - mice were on calorie-restricted diets for their whole lives, while those that exercised did so for just the month late in life - [the researchers] cautioned against drawing conclusions about the effectiveness of exercise versus calorie restriction in preventing or reversing synaptic damage. longer periods of exercise might have more profound effects."

ISSUES WITH IMMORTALITY, REVISITED (August 03 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4838
"Immortality" is a problematic term, and the press insist on using it when talking about efforts to extend healthy life: "As with cryonics, a proposal to extend life substantially is greeted with bizarre concerns about living too long, or the wrong people living longer. Why not apply such complaints to ordinary medical gains? A big part of the problem, I think, is that talk of 'immortality' invokes an extremely far view. But finite increases in lifespan really have little to do with immortality. Immortality means you never die, ever. But forever is a really really long time! In fact, nothing you can imagine is remotely as long. A thousand year lifespan would be fantastic, relative to our lifespan. I want it! But it is nothing like immortality. It would have clear stages, and a very real end to anticipate. Anyone with a halfway decent imagination couldn't remotely run out of new interesting things to do, places to visit, people to see, etc. Yes they'd have time for twenty times as many careers, hobbies, marriages, and vacations as we do now, but it should only take a moment's reflection to realize you there are far more than twenty times as many things to do than we manage in our lives. For example, any decent library holds twenty times more books than you've ever read."

THE GUARDIAN INTERVIEWS AUBREY DE GREY (August 02 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4837
From the Guardian: "What's so wrong with getting old? It is simply that people get sick when they get older. I don't often meet people who want to suffer cardiovascular disease or whatever, and we get those things as a result of the lifelong accumulation of various types of molecular and cellular damage. This is harmless at low levels but eventually it causes the diseases and disabilities of old age - which most people don't think are any fun. Is this the biggest health crisis facing the world?

Absolutely. If we look at the industrialized world, basically 90% of all deaths are caused by aging. They are deaths from causes that affect older people and don't affect young adults. And if we look at the whole world, then the number of deaths that occur each day is roughly 150,000 and about two-thirds of them are because of aging. People have been trying to claim that we can defeat ageing since the dawn of time, and they haven't been terribly successful; there is a tendency to think there is some sort of inevitability about aging - it somehow transcends our technological abilities in principle, which is complete nonsense. And when people have made their peace with this ghastly thing that is going to happen to them at some time in the distant future, they tend to be rather reluctant to re-engage the question when someone comes along with a new idea."

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