The Aging Tree

March 2, 2012

By Robert Kane Pappas

“The Low Hanging Fruit” 

When discussing aging interventions – slowing down the aging process – note that there are causal relationships between aging, age related diseases, health span and lifespan. 

To make a further distinction, the pace of the application of various breakthroughs can be broken down into a second hierarchy: think of it as an apple tree.  There is ‘low hanging fruit’ – interventions available now such as calorie restriction and exercise (lifestyle adjustments) and substances that either mimic that caloric pathway or affect several already largely understood nexus genes that interact with that pathway; or genes relating to the insulin receptor and immune response pathways. 

We can pick that low hanging fruit from the ground right now; influence these genes (SIR1, mtor, IGF-1, Foxo3) with compounds like rapamycin, resveratrol and curcumin – and, if you up regulate or down regulate them selectively, you can increase health span and lifespan to a modest degree say 5 to 20 years.

Why is there a range of 5 to 20 years? 

The amount of increase will depend on which segment of the population, and subgroups within those segments, you are speaking about.  To make a simple model – break the population into 3 groups: the first and third groups represent a relatively small percentage of the population who have a strong genetic predisposition to either live for a very long time or have a genetic mutation or other factors which will cause them to develop a life threatening condition early on. 

For the middle group, people who have average repair gene settings, the genetic component of lifespan is 20 to 25 percent. The low hanging interventions can influence their lifespan to a greater degree. There is much room for improvement by influencing this group’s settings. 

Though scientists estimate that lifespan is about a quarter genetically impacted, according to studies of twins etc;  Dr. Nir Barzilai of Albert Einstein College of Medicine, who headed the Centenarian study – and another scientist, Dr.Stephen Austad of the Barshop Institute for Longevity and  Aging Studies – make a further distinction about these population groups.

In the outliers, for instance, they say, – ‘people who live a very long time the genetic component of lifespan is far higher”.  In these individuals, the genes referred to above are already naturally in a setting that confers longevity.  These people either never get sick (many of Barzilai’s centenarians have smoked for 80 or even 90 years) or they always get better (their nexus repair genes are more active). And most of their close relatives live a long time. Thus for these outliers, the low hanging fruit is likely to have a modest effect on their lifespan, perhaps 5 years. The centenarians have a very square healthspan/lifespan graph – meaning that they stay active and healthy for the vast majority of their long lives – they have a short period of sickness and then they die. 

Dr. Leonard Guarente of MIT explained to me that his research would lead to a leveling of the population’s healthspan and lifespan; giving people who were not blessed with great gene settings a significant lengthening of health span and lifespan.  

How long? The guess, here in terms of the low fruit, is 10-20 years. And – it is not clear whether tweaking a number of these genes would have a cumulative effect. Probably not – because these pathways are largely overlapping – though there may be an additive affect. 

The near term economic and political impact of the extension of lifespan and health span is another subject. 

“The Middle Fruit Level” 

From here on it gets a bit tricky – much like predicting a storm more than 5 days in advance. Note well though, the storm is coming. 

The time frame estimate is that implementation of the next level, “the middle fruit” will begin within 10 years, though maybe not for the general public – and that too is another story.  

Within 10 years Big Pharma will have created patented analogues of compounds that influence these genes; approved by the FDA for various conditions.  The increase in lifespan will be a side effect. But – within that period – it will be impossible to prove this in human studies because (obviously) of the length of time involved. 

When you go to an apple orchard, you often see step ladders and extension poles used to retrieve fruit beyond a person’s reach. Over the past twenty years the molecular biologists have developed new tools.  For example, genomic mapping has gone from costing 100’s of millions of dollars to a couple thousand, and will soon cost 100’s. Coupled with the speed of modern computing and algorithms, scientists can address the higher level of aging research – that being extending lifespan/healthspan beyond the traditional wall of 120 years. 

Two questions: 

1- Why will they be able to do that? 

2- Do all the scientists think that? 

I will give short answers to each and then elaborate in turn. 

Addressing the former question – Scientists will be able to do this because the level of nature that needs to be intervened with does not conflict with evolution. Lifespan already increases 5 hours a day. Several scientists who I spoke with said that they were very surprised “just how easy it is to change lifespan.”   

This is not a breaking the speed of light level question. 

Stem cell reversal?  Smart M.D.’s are, themselves, shocked at what is suddenly possible with regard to stem cells – and we’re not talking about embryonic stem cells (a source of political wrangling) – we’re talking about taking a bit of your skin or blood or other cells, and reverting them back to a state of early development, where these cells can become (differentiate) into a younger version of that organ. 

Or, researchers have changed the environment (signaling) of a cell, say a muscle cell, and it has acted younger, become younger, on its own without surgery. And these cells and tissues are yours – not transplants – so there is no issue of rejection.  Moreover, these cells will at some point be able to be corrected for genetic defects.  So – if a heart muscle or some organ had a mutation – they will correct that mutation, and the replacement won’t be the lemon that person was born with. 

There are – by definition – always unintended consequences.  I will briefly address this issue when I speak of the fruit at the top of the aging tree. This level of discussion suffices for now. 

Within the middle fruit level, global cures for alzheimer’s and cancer will be developed. In part, the answers will have to do with mimicking the processes of organisms and animals that never get cancer – for instance – the naked mole rat.  Try as they will, scientists have been unable to give this animal cancer, no matter what they do. Naked mole rats have double P16 genes, this insures that cells don’t get too close.  Again, better versions of what we already have. They also live ten times longer than their close cousins. 

We’re not talking about having to grow wings in order to manage or cure cancer. There is a tribe in South America (they are very short) who have a mutation in their IGF-1 receptor.  They hardly ever get cancer.  So global cancer cures will have to do with piggy backing and delivering on what is now known.  

Delay aging and in most cases you delay or ameliorate virtually all disease including cancer. 

Cancer permanently turns on a gene called telomerase, making it immortal.  There is much research focusing on new therapies via telomerase manipulation. 

Controlling and alleviating cell senescence will be harvested on the second level of hanging fruit. This will impact both cancer, inflammation, and by extension, tissue aging itself. 

Research in mitochondrial biogenesis will impact the normally dwindling energy supply of the mitochondria, the power plants of our cells. 

Changing average Telomere length is still an open question in regard to whether it is a cause or an effect or both – vis a vis aging and lifespan; and its relationship to cancer is still not fully known. 

Dr. Stephen Austad discovered opossums who lost their predators. Over a period of time they developed longer lifespans, had an additional litter.  This suggests that genes and systems concerning the flight/fight response affect lifespan. 

What about the answer to the second question? 

“Do scientists think we can break the 120 year barrier in the near future?” 

I think that most do.  Some don’t. What is certain is that few will admit it – at least to the Mainstream News Media. 

A scientist can only ruin his career by saying so. Careers are never ruined by not opening your mouth, by playing it safe. I have found that the higher the scientific profile, the more conservative the public estimates. 

Because I am not a journalist I have heard things scientists don’t tell journalists. And I have seen them finesse journalists about issues – things they told me differently about off the record. 

This goes to how the media reports these advances; and that too is another subject, as is the relationship between government, research lab, biotech company and the drug companies – and its impact on the rate of progress. 

“The Fruit at the Top of the Tree”

At the third level of fruit the questions get weirder. 

Major issues set the backdrop for any discussion: 

     * Unintended consequences 

     * The speed of advancement. 

     * Do humans want to live indefinitely? 

     * The larger social and political and psychological  questions.  

These questions permeate all levels of fruit harvesting, especially for the public at large. My film series will address these factors – with regard to the various stages of the scientific application. 

“The speed of advancement” 

This question is addressed well by Aubrey De Grey Ph.D. He believes that very soon, perhaps 20 years out; we will begin to outrun aging.  The advances will outpace what is going wrong, and death due to aging and disease will become an indefinite thing. 

Actual age reversal was something – that, when I first heard of it 5 years ago – I put in the category of time travel and ghosts. 

But recent research into germ cells (babies are born at zero) and menopause reversal, creation of new eggs etc. says that this will be on the table in around 20 years. And then all bets will be off. 

The interfacing of nano technology, computer technology – with the organic will become an issue. 

“Unintended consequences” can be grouped into questions concerning genetic consequences, and to the larger global environment, from population and resource issues, to politics and religion.   

Without those questions being asked soon, we won’t survive long enough to reap the fruit of this new science. 

After 5 years of interviewing the researchers and poking around labs with my camera, it is not a question of if but when.  The general population has little idea of what is about to befall them.

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The Oblivious Public – Longevity Medicine
March 4, 2012 at 11:50 am
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blox.pl October 15, 2014 at 9:31 am

Great post. I’m facimg many of these issues as well..

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