Tag Archives: muscle

by

Mitochondrially Targeted Antioxidant SS-31 Reverses Some Measures of Aging in Muscle – Article by Reason

No comments yet

Categories: Science, Technology, Transhumanism, Tags: , , , , , , , , , , , , , , , ,

The New Renaissance Hat
Reason
May 26, 2013
Recommend this page.
******************************

Originally published on the Fight Aging! website.

Antioxidants of the sort you can buy at the store and consume are pretty much useless: the evidence shows us that they do nothing for health, and may even work to block some beneficial mechanisms. Targeting antioxidant compounds to the mitochondria in our cells is a whole different story, however. Mitochondria are swarming bacteria-like entities that produce the chemical energy stores used to power cellular processes. This involves chemical reactions that necessarily generate reactive oxygen species (ROS) as a byproduct, and these tend to react with and damage protein machinery in the cell. The machinery that gets damaged the most is that inside the mitochondria, of course, right at ground zero for ROS production. There are some natural antioxidants present in mitochondria, but adding more appears to make a substantial difference to the proportion of ROS that are soaked up versus let loose to cause harm.

If mitochondria were only trivially relevant to health and longevity, this wouldn’t be a terribly interesting topic, and I wouldn’t be talking about it. The evidence strongly favors mitochondrial damage as an important contribution to degenerative aging, however. Most damage in cells is repaired pretty quickly, and mitochondria are regularly destroyed and replaced by a process of division – again, like bacteria. Some rare forms of mitochondrial damage persist, however, eluding quality-control mechanisms and spreading through the mitochondrial population in a cell. This causes cells to fall into a malfunctioning state in which they export massive quantities of ROS out into surrounding tissue and the body at large. As you age, ever more of your cells suffer this fate.

In recent years a number of research groups have been working on ways to deliver antioxidants to the mitochondria, some of which are more relevant to future therapies than others. For example gene therapies to boost levels of natural mitochondrial antioxidants like catalase are unlikely to arrive in the clinic any time soon, but they serve to demonstrate significance by extending healthy life in mice. A Russian research group has been working with plastinquinone compounds that can be ingested and then localize to the mitochondria, and have shown numerous benefits to result in animal studies of the SkQ series of drug candidates.

US-based researchers have been working on a different set of mitochondrially targeted antioxidant compounds, with a focus on burn treatment. However, they recently published a paper claiming reversal of some age-related changes in muscle tissue in mice using their drug candidate SS-31. Note that this is injected, unlike SkQ compounds:

Mitochondrial targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice

Quote:

Mitochondrial dysfunction plays a key pathogenic role in aging skeletal muscle resulting in significant healthcare costs in the developed world. However, there is no pharmacologic treatment to rapidly reverse mitochondrial deficits in the elderly. Here we demonstrate that a single treatment with the mitochondrial targeted peptide SS-31 restores in vivo mitochondrial energetics to young levels in aged mice after only one hour.

Young (5 month old) and old (27 month old) mice were injected intraperitoneally with either saline or 3 mg/kg of SS-31. Skeletal muscle mitochondrial energetics were measured in vivo one hour after injection using a unique combination of optical and 31 P magnetic resonance spectroscopy. Age-related declines in resting and maximal mitochondrial ATP production, coupling of oxidative phosphorylation (P/O), and cell energy state (PCr/ATP) were rapidly reversed after SS-31 treatment, while SS-31 had no observable effect on young muscle.

These effects of SS-31 on mitochondrial energetics in aged muscle were also associated with a more reduced glutathione redox status and lower mitochondrial [ROS] emission. Skeletal muscle of aged mice was more fatigue resistant in situ one hour after SS-31 treatment and eight days of SS-31 treatment led to increased whole animal endurance capacity. These data demonstrate that SS-31 represents a new strategy for reversing age-related deficits in skeletal muscle with potential for translation into human use.

So what is SS-31? If look at the publication history for these authors you’ll find a burn-treatment-focused open-access paper that goes into a little more detail and a 2008 review paper that covers the pharmacology of the SS compounds:

Quote:

The SS peptides, so called because they were designed by Hazel H. Sezto and Peter W. Schiler, are small cell-permeable peptides of less than ten amino acid residues that specifically target to inner mitochondrial membrane and possess mitoprotective properties. There have been a series of SS peptides synthesized and characterized, but for our study, we decided to use SS-31 peptide (H-D-Arg-Dimethyl Tyr-Lys-Phe-NH2) for its well-documented efficacy.

Studies with isolated mitochondrial preparations and cell cultures show that these SS peptides can scavenge ROS, reduce mitochondrial ROS production, and inhibit mitochondrial permeability transition. They are very potent in preventing apoptosis and necrosis induced by oxidative stress or inhibition of the mitochondrial electron transport chain. These peptides have demonstrated excellent efficacy in animal models of ischemia-reperfusion, neurodegeneration, and renal fibrosis, and they are remarkably free of toxicity.

Given the existence of a range of different types of mitochondrial antioxidant and research groups working on them, it seems that we should expect to see therapies emerge into the clinic over the next decade. As ever, the regulatory regime will ensure that they are only approved for use in treatment of specific named diseases and injuries such as burns, however. It’s still impossible to obtain approval for a therapy to treat aging in otherwise healthy individuals in the US, as the FDA doesn’t recognize degenerative aging as a disease. The greatest use of these compounds will therefore occur via medical tourism and in a growing black market for easily synthesized compounds of this sort.

In fact, any dedicated and sufficiently knowledgeable individual could already set up a home chemistry lab, download the relevant papers, and synthesize SkQ or SS compounds. That we don’t see this happening is, I think, more of a measure of the present immaturity of the global medical tourism market than anything else. It lacks an ecosystem of marketplaces and review organizations that would allow chemists to safely participate in and profit from regulatory arbitrage of the sort that is ubiquitous in recreational chemistry.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.  

This work is reproduced here in accord with a Creative Commons Attribution license.  It was originally published on FightAging.org.

by

Update to Resources on Indefinite Life Extension – July 10, 2012

No comments yet

Categories: Announcements, Science, Transhumanism, Tags: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

TRA’s Resources on Indefinite Life Extension page has been enhanced over the past two months with links to numerous fascinating articles and videos.

Articles

– “Scientists turn skin cells into beating heart muscle” – Kate Kelland – Reuters – May 22, 2012

– “Is Amyloidosis the Limiting Factor for Human Lifespan?” – Lyle J. Dennis, M.D. – Extreme Longevity – May 22, 2012

– “Israeli scientists create beating heart tissue from skin cells” – The Telegraph – May 23, 2012

– “Paralyzed rats walk again in Swiss lab study” – Chris Wickham – MSNBC.com – May 31, 2012

– “New Cancer Drugs Use Body’s Own Defenses” – Ron Winslow – Wall Street Journal – June 1, 2012

– “Bristol immune drug shows promise in three cancers” – Julie Steenhuysen – Reuters – June 2, 2012

– “Prostate cancer drug so effective trial stopped” – Victoria Colliver – San Francisco Chronicle – June 2, 2012

– “New ‘smart bomb’ drug attacks breast cancer, doctors say” – Associated Press – June 3, 2012

– “Alzheimer’s vaccine trial a success” – Karolinska Institutet – June 6, 2012

– “Man Cured of AIDS: ‘I Feel Good’” – Carrie Gann – ABC News – June 8, 2012

– “Artificial Lifeforms Promise Cleaner World, Healthier Humans” – Dick Pelletier – Positive Futurist – June 9, 2012

– “Secret of ageing found: Japanese scientists pave way to everlasting life” – RT – June 9, 2012

– “How aging normal cells fuel tumor growth and metastasis” – Thomas Jefferson University – June 14, 2012

– “People Who Justify Aging are Profoundly Wrong – Aging is Abhorrent” – Maria Konovalenko – Institute for Ethics & Emerging Technologies – June 14, 2012

– “Scientists tie DNA repair to key cell signaling network” – University of Texas Medical Branch at Galveston – June 15, 2012

– “Deciding How We Age as We Age” – Seth Cochran – h+ Magazine – June 19, 2012

– “How we die (in one chart)” – Sarah Kliff – Washington Post – June 22, 2012

– “Modified humans: the most cost-efficient way to colonize space” – Dick Pelletier – Positive Futurist – June 2012

– “Japanese Scientists Grow Human Liver From Stem Cells” – Reuters and Singularity Weblog – June 2012

– “Why Do Naked Mole Rats Live So Long? Do they hold the key to human life extension?” – Maria Konovalenko – Institute for Ethics & Emerging Technologies – June 29, 2012

– “Scientists Develop Alternative to Gene Therapy” – ScienceDaily – Scripps Research Institute – July 1, 2012

– “How to live beyond 100” – Lucy Wallis – BBC News – July 2, 2012

– “Earth 2050-2100: longer lives; new energy; FTL travel; global village” – Dick Pelletier – Positive Futurist – July 3, 2012

– “Scientists discover bees can ‘turn back time,’ reverse brain aging” – Phys.org – Arizona State University – July 3, 2012

– “Secret formula may be key to reverse aging” – Mike Holfeld – Click Orlando – July 4, 2012

– “Is there a biological limit to longevity?” – Aubrey de Grey – KurzweilAI – July 5, 2012

– “Demystifying the immortality of cancer cells” – Medical Xpress – July 5, 2012

– “Suggesting a Test of Rapamycin and Metformin Together” – Reason – FightAging.org – July 5, 2012

– “Earth 2050-2100: Longer Lives; New Energy; FTL Travel; Global Village” – Dick Pelletier – Positive Futurist – July 7, 2012

Videos

Aubrey de Grey

Aubrey de Grey – Aging & Suffering – Interview with Adam Ford – May 31, 2012

Nikola Danaylov (Socrates)

Anders Sandberg on Singularity 1 on 1: We Are All Amazingly Stupid, But We Can Get Better – May 27, 2012

Hugo de Garis on Singularity 1 on 1: Are We Building Gods or Terminators? – June 2012