Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: life extension – Page 545

Reversing wrinkled skin and hair loss in mice

Mitochondrial dysfunction is associated with many mitochondrial diseases, most of which are the result of dysfunctional mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS accounts for the generation of most of the cellular adenosine triphosphate (ATP) in a cell. The OXPHOS function largely depends on the coordinated expression of the proteins encoded by both nuclear and mitochondrial genomes. The human mitochondrial genome encodes for 13 polypeptides of the OXPHOS, and the nuclear genome encodes the remaining more than 85 polypeptides required for the assembly of OXPHOS system. Mitochondrial DNA (mtDNA) depletion impairs OXPHOS that leads to mtDNA depletion syndromes (MDSs)1, 2. The MDSs are a heterogeneous group of disorders, characterized by low mtDNA levels in specific tissues. In different target organs, mtDNA depletion leads to specific pathological changes. MDS results from the genetic defects in the nuclear-encoded genes that participate in mtDNA replication, and mitochondrial nucleotide metabolism and nucleotide salvage pathway1, 4,5,6,7,8,9,10. mtDNA depletion is also implicated in other human diseases such as mitochondrial diseases, cardiovascular11, 12, diabetes13,14,15, age-associated neurological disorders16,17,18, and cancer19,20,21,22,23,24,25.

A general decline in mitochondrial function has been extensively reported during aging26,27,28,29,30,31,32,33. Furthermore, mitochondrial dysfunction is known to be a driving force underlying age-related human diseases16,17,18, 34,35,36. A mouse that carries elevated mtDNA mutation is also shown to present signs of premature aging37, 38. In addition to mutations in mtDNA, studies also suggest a decrease in mtDNA content and mitochondrial number with age27, 29, 32, 33, 39. Notably, there is an age-related mtDNA depletion in a number of tissues40,41,42. mtDNA depletion is also frequently observed among women with premature ovarian aging43. Low mtDNA copy number is linked to frailty and, for a multiethnic population, is a predictor of all-cause mortality44. A recent study revealed that humans on an average lose about four copies of mtDNA every ten years. This study also identified an association of decrease in mtDNA copy number with age-related physiological parameters39.

To help define the role of mtDNA depletion in aging and various diseases, we created an inducible mouse expressing, in the polymerase domain of POLG1, a dominant-negative (DN) mutation that induces depletion of mtDNA in the whole animal. Interestingly, skin wrinkles and visual hair loss were among the earliest and most predominant phenotypic changes observed in these mice. In the present study, we demonstrate that mtDNA depletion-induced phenotypic changes can be reversed by restoration of mitochondrial function upon repletion of mtDNA.

The Freedom of Life Extension

Life extension would allow everyone to enjoy a higher degree of freedom.

Freedom is a rather big deal in this age. We want freedom of speech, political freedom, press freedom, religious freedom, and freedom of choice over anything that may concern us directly. Different kinds of freedom are available in different amounts in different areas of the world, and while many people tend to see the glass half empty and complain that freedom is not equally distributed everywhere, it’s undeniable that we enjoy far greater liberty than previous generations. It’s not always easy to act upon your choices, and sometimes you’re free to choose in theory but not in practice, but overall, we enjoy options that who came before us couldn’t even dream of.

Take health, for example. Two hundred years back, if you didn’t want to get the flu, or any other infectious disease, you didn’t have the option not to do so. The mechanism through which infectious diseases manifest and spread wasn’t even remotely understood, so you didn’t have any idea what you should or shouldn’t do to minimize your risk of falling ill; basic hygiene wasn’t exactly a standard, and drugs and vaccines were nowhere in sight. If you actively wanted to do something to prevent getting the flu—which, at the time, might have killed you—you simply didn’t have this option.

Today, however, if you want to avoid infectious diseases, you have plenty of options to do so. Hygiene is common in most of the world, and there are vaccines available. You may well choose to not care, live in filth, and never get even a flu shot, but you do have the option. It’s a choice that, two hundred years back, could simply not be made. Depending on where you live and your access to medical care, acting upon your choice can be difficult, but this is a different matter. The option of preventing disease exists, and in principle, you may avail yourself of it, unlike in the past, when the option wasn’t there to begin with.

Not classing aging as a disease is not a major problem

A common concern in the community is that the FDA, the EMA, and other bodies, such as WHO, do not classify aging as a disease and that this poses a problem for developing therapies that target aging. However, this is not really as serious an issue as some people would suggest; today, we will have a look at why that is.

Why this will not stop progress

Aging is a variety of distinct processes, damages, and errors; therefore, simply treating aging in clinical terms is not a viable endpoint. For a clinical trial to be conducted, it requires a verifiable indication, and aging is too general for the FDA and EMA to classify it as a disease.

Celebrating Success at Our First Conference

We brought the leading experts in aging research and biotech investment together for an action-packed day of science. See what happened at this exciting event and check out our first event video now.

On July 12th, we hosted our first conference, Ending Age-Related Diseases: Investment Prospects & Advances in Research, at the Frederick P. Rose Auditorium, which is part of the Cooper Union campus in New York City. We are delighted to announce that the conference was a huge success with 160 attendees, a wide variety of speakers from both research and business, and some great discussion panels.

The goal of this conference was to promote multidisciplinary collaboration in order to foster the development of next-generation drugs and therapies that directly target the processes of aging and thus have the potential to prevent and cure age-related diseases.

For those of you who could not join us there, we have recorded the talks and panels from the conference, and we will be making them available on our website in the next few weeks once we have edited them. As a special thank you, the Lifespan Heroes, our monthly patrons, will be offered early access to these videos ahead of a public release.

A Novel Gene Therapy To Treat One Of The World’s Biggest Growing Chronic Disease: Dementia and Alzhiemer’s

The brain is about 10% neurons and 90% neural network support cells, called neuroglia, or glial cells, which surround and insulate neurons, protect them from damage, and supply them with nutrients and oxygen. Neuroglia are often found to malfunction in neurological disorders such as Alzheimer’s Disease or amyotrophic lateral sclerosis (ALS).

Research studies indicate that telomerase gene therapy may not only reverse Alzheimer’s Disease and other dementias, but it may even protect people from developing such diseases.

This is indeed hopeful news for the nearly 50 million victims of Alzheimer’s or related dementia worldwide as well as for the millions of aging people with Parkinson’s and aging-related mental decline.

Telomerase gene therapy appears to rejuvenate microglial (the immune cells of the brain) cells in Alzheimer’s Disease according to promising research study data.

Enough with the excuses

Excuses for age-related death are just that: excuses.

The knowledge that every ambition is doomed to frustration at the hands of a skeleton has never prevented the majority of human beings from behaving as though death were no more than an unfounded rumor.

The quote above is by Aldous Huxley. It sums up very well humanity’s attitude towards death, and interestingly, it can be interpreted in two opposite ways: praise for the human ability to soldier on, even in the face of inevitable demise, or a short, withering remark on how delusional we can be that, if we just ignore it really hard, maybe we don’t need to worry about death.

When I see people professing with apparently unshakable conviction the necessity of death, their not fearing it, or that—as they sometimes say in my hometown when somebody dies—” those who live have it worse”, I can’t help but think that the better interpretation of Huxley’s quote is the second one.

Minoring in the majors

It’s in a bad taste to say that other global issues are more urgent than ageing, when pretty much all global issues—ageing included—affect the life, and the quality of life, of many people.

Suppose you’re in your mid-seventies, and you find out that your aortic valve doesn’t work very well. Undergoing a replacement operation—nowadays, a relatively simple and safe procedure—is not only going to help you with your unpleasant episodes of fatigue, chest pain, and dizziness, it may well save your life, minimizing your risk of sudden cardiac arrest.

Your doctor suggests that you undergo the procedure and sends you to a surgeon for the operation; however, when you get there, the surgeon starts yelling at you that, rather than using resources to replace your valve and extend your life, we should fund initiatives to save children in poor countries, build health clinics, train midwives, and fight for equal opportunity and for women’s rights. He then goes on rambling that, until these issues are addressed, he doesn’t want to hear about extending your natural lifespan—after all, since you’re in your mid-seventies, you’re well above the world’s average lifespan; he shoos you and your family out and slams the door on you.

The chances are good that you’d think this person was several sandwiches short of a picnic; you would report him and have him fired for malpractice. Thankfully, you’re not very likely to run into a surgeon like that, but you are likely to bump into people contending the exact same things as the mad surgeon when you replace heart surgery—a very specific form of life extension—with the general concept of life extension. Why is that?

These anti-aging pills look like they’re actually working

Pills hailed as the first real “anti-aging” drugs inched a little closer to the market after a study found they cut the number of respiratory infections in the elderly by half.

The drugs: The pills act on an aging-related pathway called TORC1. Inhibiting this pathway “has extended life span in every species studies to date” (like mice and worms), according to Joan Mannick, who lead the study for drug giant Novartis.

Will humans live longer, too? Maybe. But that will take time to figure out. For now, what’s known is that giving people 65 and older these drugs seems to boost their immune function. Elderly people taking the drugs got about 40 percent fewer colds or bronchial infections. About 264 people got the drugs over six weeks and then were tracked for a year.

/* */