Lifeboat Foundation

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 pathway^{1, 4,5,6,7,8,9,10}. mtDNA depletion is also implicated in other human diseases such as mitochondrial diseases, cardiovascular^{11, 12}, diabetes^13,14,15, age-associated neurological disorders^16,17,18, and cancer^{19,20,21,22,23,24,25}.

A general decline in mitochondrial function has been extensively reported during aging^{26,27,28,29,30,31,32,33}. Furthermore, mitochondrial dysfunction is known to be a driving force underlying age-related human diseases^{16,17,18, 34,35,36}. A mouse that carries elevated mtDNA mutation is also shown to present signs of premature aging^{37, 38}. In addition to mutations in mtDNA, studies also suggest a decrease in mtDNA content and mitochondrial number with age^{27, 29, 32, 33, 39}. Notably, there is an age-related mtDNA depletion in a number of tissues^40,41,42. 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.

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.

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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.

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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.

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New video from Undoing Aging 2018: Doug Ethell, Founder and CEO of Leucadia Therapeutics, presenting: Alzheimer’s Disease Begins as a Fixable Plumbing Problem.

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.

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

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.

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Drugs were created to block a protein called the mammalian target of rapamycin (mTOR) and it boosted the immune system by about 40% in elderly people.

They safely reducing infections in elderly volunteers around 40% by enhancing the immune system.

In 2004, tests that blocked a similar enzyme in fruit flies gave them a longer lifespan.

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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.

Continue reading “Minoring in the majors” »