Sunday, November 13, 2022

Lifespans of 100+ are a reasonable assumption

Most life expectancy tables do not distinguish on the basis of income, which have an effect on lifespan.  Of these, income has the greatest effect and it is increasing over time, as well.  At age 65, the sex difference has decreased from 4.2 to 2.4 years.  The difference between white and black has decreased from 1.4 years to 1.1.  However, during the same time, as we see below, for white 50 year old males, the difference between the lowest and highest quintile has increased from around 6 years to 12.7 years.  Furthermore, the upper 40% of 50 year old males are experiencing an increase in lifespan of about 2.25 years per decade compared to 1.6 years per decade for males in total.  



Because of this, not surprisingly, U.S. Presidents, who are primarily white males and well into the upper quintile of income are now living well into their 90s. Gerald Ford and Ronald Reagan,  died at 93, George H.W. Bush lived to 94 and Jimmy Carter has already managed 97.  This, however, as would be expected, is a new phenomenon.  Prior to these four, only John Adams made it to 90 and only just.  So, the last three Presidents to die have also been the three oldest Presidents and Jimmy Carter will exceed all of those.  


The break-point seems to be for those born around 1910. The four Presidents before Ford, Bush, Reagan and Carter (not including Kennedy) lived to an average of 78 or 15 years less.  These are small data sets and, consequently, not very trustworthy.  Since the break point seems to be around 1910, I decided to look at lists of other prominent people in government and see if the trend continues.  

Vice Presidents are problematical because they often become President.  So, I looked at Secretaries of State.  There are nine born after 1910 that I counted, three of whom are still alive, but in their 90s.  The data set averages 88, compared to the preceding nine who lived, on average, to 76.   This is not as exaggerated, but it still is a 12 year difference.  Three of the nine are still alive, so ultimately, this could approach the age of the last four Presidents.

https://www.aeaweb.org/conference/2016/retrieve.php?pdfid=1025

The men who were 50 38.8 years prior to 2010 are now dying at aged 88.8.  To clarify, the subject men were born in 1921.  However, if you are 50 now you were born in 1972 or 51 years later.  As we see, the  life expectancy has been increased by .225 years per year or 51X.225=11.5 years.  That means the 50 year old of today, in the target group has a life expectancy of 88.8+11.5=100.3

So, if you are a man, around 50 years old and in the upper two quintiles in income, you should expect to live well into your 90s and quite possibly into your 100s.  That is without any extraordinary medical breakthroughs.  That is just based upon current trends.  Oddly, that expectation doesn't change much with your age.  That is because, if you are under 50, you have a non-zero chance of dying before you reach 50 and if you are over 50, you have a higher life expectancy because you survived to an age over 50.  So, for example, a 72 year old man who was in the top two quintiles when he was 50, still has a life expectancy of 98.3 or only 1.3 years less than the 50 year old even though he is twenty years older. 

But, that is not the end of it.  There are reasons to believe that the linear increase in life expectancy of .225 years per year could start to level out.  Admittedly, it includes all men and is just a 7 year trend but the CDC chart appears to be leveling off at about 87 years.  A growing percentage of people in their 90s are reaching the end of the road with technologies reducing early death from cancer and heart disease.  Additional increases may require dealing with what appear to be the most common causes of death for people over 100.  These are frailtyAlzheimer's Disease and Disseminated Amyloidosis.  The success in treating these diseases and extending life expectancy past the mid-90s or so may result in a different trajectory in life expectancy increase.  Of course, it could be faster or slower.

It is now understood that progressive resistance strength training substantially postpones frailty.  However, the loss of mitochondria, cell senescence and sarcopenia, the underlying causes of frailty can be delayed through exercise but, ultimately, increasing age will overcome the benefit.  More needs to be done in order to decrease frailty over the age of 100.  Part of the cause of mitochondrial malfunction has to do with the failure of autophagy especially mitophagy.  There is strong evidence that cellular senescence contributes to mitochondrial dysfunction and may be a primary contributor to gerontological frailty.

Fortunately, the health problems associated with aging due to the accumulation of senescent cells appear to be on the verge of a solution.  Over the last decade research has demonstrated that clearing senescent cells from aged mice dramatically returned them to a more youthful phenotype.  Of course, the mechanisms may be useful in short lived animals but not in humans.  However, there is an accumulating body of evidence that cellular senescence may be the cause of much of the elder phenotype in humans.  However, senolytics, while eliminating senescent cells, also eliminate healthy ones and further research is needed.

Two FDA approved drugs, Metformin and Rapamycin also appear to extend lifespan.  

Metformin, prescribed to treat type 2 diabetes was found in a retrospective study to extend life expectancy in T2DM patients, over time, to above that of the general population.  With typical scientific conservatism, trials were started with mouse models and have now progressed to human trials.  Initial results suggest that it probably does slow aging.  It is being speculated that it stimulates the same physiological responses as calorie restriction, a long known technique for life extension.  There are also suggestions that it may improve the energy pathways.

Rapamycin, an immunological suppressant used in organ transplants, also appears to have, in lower doses, anti-aging effects.  In middle aged mice, a 90 day course of rapamycin increased median life expectancy by 60%.  However, genetically heterogenous mice, while still experiencing a statistically significant increase in  lifespan, had substantially less increase.  Of course, as is the case with virtually all research using mouse models, the response is far more dramatic than it is in humans.  The use and positive results of a 90 day course of treatment confounds the generally accepted assumption that Rapamycin extends lifespan by reducing the incidence of cancer.

Of these three regimens, two of which are deliverable in 90 day chemotherapy treatments, the senolytics seem to be the most effective in modifying the elderly phenotype, while Metformin and Rapamycin extend lifespan, they may not necessarily extend healthspan.  

As stated earlier there are reasons to believe that, in the absence of fundamental breakthroughs, life expectancy may be asymptotic just above 100.  One study that applied the Gompertz law to human senescence rate found an asymptote at 104.  However, since senolytics clear accumulated senescent cells, that technology, if successful, may lift or even eliminate that limit to lifespan.  

A University of Michigan postmortem study of 7 supercentarians found that 6 of them died of amyloidosis, a disease closely related to Alzheimer's.  In combination with a senolytic therapy, this could result in much longer lifespans.  How much longer is difficult to determine because, until people routinely exceed 115, we cannot be sure what further medical challenges may surface.  It is only in the last decade that amyloidosis has surfaced as a problem to be solved.

We see that extending current trends for the top 40% of the population in income leads to life expectancy of just under 100 for men and just over 100 for women.  This life expectancy only increases slightly for young people (~30) compared to older people (~70).  We hope that this lifespan will be driven down to lower income levels until they are routine for everyone.  However, the reasons for lower life expectancies among lower income men are not clear. 

Healthspans also are likely to increase, partially from an understanding that exercise slows ageing and partially from senolytics.  While life expectancy over 100 and possibly over 115 is possible, it will rely upon medical breakthroughs that, while currently under study and promising, are not yet demonstrated.

So, my current assessment is that people today should plan on living to about 100 (with the understanding that there is a wide distribution) and, if so inclined, realistically hope for 115 or more.



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