Dear Future Centenarian,
Last weekend, I went to a hospital… TWICE.
Friday eve, I was scheduled for minor surgery. Then Sunday, I had to go to the ER due to a post op complication.
Now, it all sounds worse than it was. I’m totally fine. But what the weekend did do was give me time to think and OBSERVE.
Lots of time lost because the surgeon was running 2½ hours behind, and the procedure took longer than anticipated. Eight hours total on Fri.
And since I couldn’t get internet or cell phone service, and because I didn’t feel like watching TV, I watched something else… patients.
Same thing on Sunday. As you know, ERs aren’t known for express lanes. I had hours to kill, so I watched more.
And the more I saw, the more I was reminded how much aging sucks.
The patient population seemed largely elderly. And for the most part, it looked like they were suffering and/or sedated as they went back and forth on their guernseys or wheelchairs.
It’s gut wrenching to see so much suffering in one place. And this was just one hospital out of thousands in the US alone. And a bit frightening to be one of those patients.
To the hospital staff, patient flow must resemble a moving parade. Especially in nursing homes. Patients come from all walks of life, their active youthful years behind them for good. Now mere memories for them to cling to.
The present isn’t pleasant. And their futures are short and dismal. The end is near, and the final path might include years of ever-increasing suffering.
Then new crops for the staffs.
This is why I formed Maximum Life Foundation and helped launch BioViva USA. When I met Liz Parrish, BioViva’s CEO, one of the first things out of her mouth was that she was committed to ending pain and suffering.
I can’t think of a more noble purpose of life.
The single biggest cause of pain and suffering is aging. Solve aging, and 90% of deadly and crippling diseases will simply never materialize.
Almost 50 years ago, a very wise man told me… the ultimate cure is prevention.
Rolling back the clock, rejuvenating and keeping aging at bay will be the single biggest all-time boon to humanity.
Who wants to endure pain and suffering? Who wants to slowly deteriorate until they die? Who wants to spend their life savings to gain a few crappy years tacked on to our terminal stages?
No one in their right mind.
I guarantee, EVERY sane patient I saw last weekend would trade all their possessions to be biologically young and healthy again.
Sure, we all want that, but until we experience an aging related condition or disease do we want it passionately. DESPERATELY actually.
So what are you doing to help make this happen, at least for you?
If you’re not donating to or investing in longevity research, I hope you are at least an advocate. Are you supporting Life Extension Foundation or helping spread the word about life extension conferences such as the RAADfest www.raadfest.com?
In all cases, whether or not you are doing any of the above, I hope you are following healthy lifestyle habits and incorporating some of the longevity breakthrough revealed at the RAADfest last month.
Because make no mistake about it, an aging cure is approaching. And everything you do to tack on extra robust years gets you that much closer to full body rejuvenation.
Saturday, December 7
That’s our annual longevity party/seminar day here in Newport Beach, CA.
We’re almost sold out, so get your tickets now if you plan on attending.
We hope you can join us kick off the holiday season. We look forward to seeing you!
Seminar: 4:00-6:00 PM with six 15-minute presentations
Holiday party: 6:00-9:00 PM with heavy hors d’oeuvres and open bar
Come for the seminar, the holiday party or both!
There is a guarded gate. Show the attendant your Eventbrite ticket or receipt.
Event to be held at the following:
Date: Saturday, December 7, 2019
Time: 4:00 PM to 9:00 PM (PST)
Location: The Clubhouse
at The Colony in Newport Beach
5100 Colony Plaza
Newport Beach, CA 92660
Poor Results from an Initial Human Trial of Nicotinamide Mononucleotide
Mitochondria are the power plants of the cell, responsible for packaging energy store molecules that power cellular processes. NAD+ is an essential metabolite for mitochondrial function, but levels decline with age.
The proximate causes of this decline are fairly well mapped, and involve insufficient resources in a variety of pathways for synthesis or recycling of NAD+. The deeper reasons are poorly understood, however, meaning how these pathway issues emerge from the underlying molecular damage to cells and tissues that causes aging.
Ways to force an increase in NAD+ levels have been shown to improve mitochondrial function in old animals, reversing some of the losses that occur with age. Loss of mitochondrial function is implicated in age-related diseases, particularly those in energy-hungry tissues such as the brain and muscles.
There are a number of ways to raise NAD+ levels:
How to Start a Biotech Company in the Longevity Industry
Based on discussions with various folk at scientific and industry conferences earlier this year, regarding whether or not our rejuvenation research, development, and advocacy community is challenging to approach and understand as an outsider, I recently put together an introductory document for entrepreneurs entitled How to Start a Biotech Company in the Longevity Industry (PDF).
Given my experiences, it is primarily aimed at entrepreneurs with previous experience in other industries, who are now interested in helping to treat aging as a medical condition and there by greatly improve the human condition.
Cellular Senescence is Important in Zebrafish Fin Regrowth
Species such as salamanders and zebrafish are capable of regrowing lost limbs, fins, and organ tissue without scarring, leading to a fully functional replacement. Regeneration from injury is in general a complex dance of different cell types: immune cells, stem cells, somatic cells. Further, senescent cells play an important part in this process.
An Interview with Matthew O’Connor, as Underdog Pharmaceuticals Secures Seed Funding
Matthew O’Conner presented at Undoing Aging earlier this year on the startup biotech company Underdog Pharmaceuticals. The company is spinning out of the SENS Research Foundation (SRF), based on research conducted by the scientific team there in recent years.
The company is focused on a class of molecule known cyclodextrins, and have candidates capable of efficiently binding and sequestering 7-ketocholesterol.
Notes on the 2019 Longevity Week Events in London
I was recently in London for the Longevity Week, a collection of single day and evening events organized by investor Jim Mellon of Juvenescence and supporting groups.
Varied events focused separately on (a) educating investors in the science of aging, (b) generating a larger investment community for the new longevity industry, and (c) improving the non-profit world and its efforts to explain the merits of treating aging to the public, to bring therapies to the clinic, and to improve the state of older life using presently available tools.
Jim Mellon clearly understands that building an industry focused on the medical control of aging, particularly in regions where medical development and clinical practice is so very heavily regulated, requires raising the water level when it comes to understanding of that industry and its potential.
The MicroRNA mir-83 Disrupts Autophagy in Aging Nematode Worms
Researchers here find a proximate cause of age-related impairments in autophagy in nematode worms. The cellular maintenance processes of autophagy, responsible for recycling unwanted and damaged molecules and structures, are well known to decline with age.
This dysfunction contributes to numerous age-related conditions, particularly in tissues containing significant populations of very long-lived cells, in which the buildup of damaged components becomes disruptive to function.
Upregulation of autophagy, on the other hand, is a feature of many interventions shown to slow aging in laboratory species. In some cases, as for calorie restriction, autophagy is required for the beneficial effects on life span.
Cardiovascular Aging Contributes to Brain Aging
The brain is an energy-hungry organ, and is sensitive to reductions in the blood supply of oxygen and nutrients.
Cardiovascular aging can reduce that supply, whether through conditions such as heart failure, or the progressive loss of density in capillary networks that occurs throughout the body with advancing age, or an accelerated pace of rupture of tiny vessels in the brain, or disruption of the blood-brain barrier, allowing unwanted molecules and cells to enter the brain.
Thus, as researchers here note, we would expect to see correlations between cardiovascular disease, or risk factors for cardiovascular disease, and damage and dysfunction in the brain.
Selectively Removing Mutant Proteins by Binding them to Autophagy Components
Researchers here demonstrate a proof of principle for an interesting approach to tackling the aggregation of damaged, altered, or misfolded proteins that is a feature of most neurodegenerative conditions.
They target the mutant huntingtin protein, which is probably an easier task than targeting, say, a misfolded protein with a normal sequence. The basic idea is to deploy a linking molecule that binds to the problem protein with high specificity, and also binds to an essential component of autophagy – in this case LC3B, involved in the generation of autophagosomes responsible for carrying materials to lysosomes.
This ensures that the whole linked set of molecules is dragged into an autophagosome and transported to a lysosome where it is broken down and recycled.
Greater Waist Circumference, Greater Risk of Dementia
In recent years, epidemiologists have found that waist circumference is a better measure of the burden of excess visceral fat tissue than body mass index (BMI).
Progress towards making better use of this information has been slow, as is usually the case in the world of epidemiology. Visceral fat tissue generates chronic inflammation through a variety of mechanisms, from DNA debris activating the immune system to inappropriate signaling by fat cells to an accelerated pace of generation of senescent cells.
Chronic inflammation disrupts function and accelerates the progression of all of the common age-related conditions. People who are overweight have a shorter life expectancy and higher lifetime medical costs as a result.
Delivery of MALAT1 in Exosomes as a Treatment for Osteoporosis
Bone is not a static tissue. It is constantly remodeled, broken down by osteoclast cells and built up by osteoblast cells. The loss of bone mass and strength with age, osteoporosis, is the result of an imbalance in the activities of osteoclasts and osteoblasts, too much destruction and too little creation.
This imbalance, as for all aspects of aging, is the result of many deeper overlapping layers of cause and effect, not fully mapped and understood.
Thus most approaches to therapy tend to involve ways to force greater activity of osteoblasts or suppress the activity of osteoclasts, rather than delving in search of root causes. The open access paper here is an example of this type of work, outlining an approach to stimulate greater osteoblast activity in mice.
Senescent Cells Mediate the Incidence of Periodontitis in Diabetic Patients
Insofar as either type 1 diabetes or type 2 diabetes increase the burden of senescent cells, we might say that the condition literally accelerates aging.
The accumulation of lingering senescent cells is a contributing cause of aging; these errant cells disrupt tissue function and produce the characteristic profile of chronic inflammation known as inflammaging via a potent mix of secreted molecules and vesicles.
Diabetic patients suffer more and worse gum disease, periodontitis, than their healthy peers, and researchers here show that hyperglycemia leads to increased numbers of senescent cells in gum tissue, causing all of the expected downstream consequences resulting from inflamed gums.
Rapamycin Prevents Deterioration in Brain Circulation in Aged Rats
The mTOR inhibitor rapamycin is well known to slow aging in animal models. As for most of the methods shown to achieve this goal in short-lived species, upregulation of cellular maintenance processes such as autophagy features prominently in the changes produced by the drug.
Every one of these approaches that produce sweeping changes in cellular metabolism and a general slowing of age-related decline provides the research community with an essentially unlimited range of projects to undertake when it comes to assessing specific metrics of aging and how they are affected.
Here, researchers look at how rapamycin affects age-related deterioration in blood circulation in the brain. There are many reasons why this might decline: a weakened or failing heart; loss of capillary network density; narrowing of blood vessels due to atherosclerosis; and so forth. The brain is an energy-hungry organ, and any reduction in the supply of oxygen and nutrients will have detrimental effects on tissue function, contributing to the onset of neurodegeneration.
The Gut Microbiome in Neuroinflammation and Alzheimer’s Disease
The microbial populations of the gut influence and are influenced by the state of the immune system. They also have effects on tissue function throughout the body via secreted compounds such as butyrate, mediating some of the effects of diet on long-term health.
These microbes change with age, losing beneficial populations and gaining harmful populations that contribute to chronic inflammation. These changes are far from fully explored at the present time, but may have effects on health that rival those resulting from regular exercise.
In this open access review, researchers discuss the influence of gut microbes on chronic inflammation of the brain, and the development of neurodegenerative conditions such as Alzheimer’s disease.
Particulate Air Pollution Correlates with Atherosclerosis Risk
It is known that exposure to airborne particles, such as smoke from cooking fires, correlates with increased mortality due to cardiovascular disease.
Setting aside commentary on wealth and its correlation with exposure to particulate air pollution, the obvious candidate mechanism is an increase in chronic inflammation due to the effects of inhaled particles on lung tissue.
Raised inflammation then leads to an accelerated progression of atherosclerosis, the fatty deposits that narrow and weaken blood vessels, ultimately leading to heart failure, stroke, and heart attack. Researchers here provide epidemiological data to support this chronic inflammation hypothesis for the harms caused by particulate air pollution.
Proposing Parkinson’s Disease to Originate in Either the Brain or the Gut
Parkinson’s disease is characterized by the aggregation and spread of misfolded ?-synuclein throughout the brain, though, as for all neurodegenerative conditions, there are many layers of cause and effect, and chronic inflammation and cellular dysfunction play noted roles as well.
There has been some debate in recent years over whether the ?-synuclein aggregation of Parkinson’s disease begins in the gut or the brain, with evidence presented for both sides. The authors of this open access paper suggest that both are the case, and Parkinson’s can be divided into two subtypes depending on the origin of ?-synuclein misfolding.