An Argument for More Focus on the Oldest Old in Research

Here an argument is made for more research into aging and its potential treatment to focus on the oldest segments of the population rather than the younger old. From the perspective of SENS and damage repair to achieve rejuvenation, I'm not sure this matters all that much: what needs to be done to treat aging under that model is well categorized and understood. The challenge is finding the funding and the will for implementation, not further delving into the unknown. From the perspective of investigating and deeply understanding the complex processes of aging, mapping the intricate chains of cause and consequence from initial damage to cells and tissues all the way through to end-stage disease, the concerns are probably more valid:

"Old people" are still being clumped together as one group, with an arbitrary cutoff of age 65. This causes several problems, for example the diseases of young elderly, less than 75-years-old, are often lifestyle-related. Diseases of young-old are primarily cancers, atherosclerotic heart diseases and diabetes. While it is laudable to spend resources ameliorating these conditions, we must face up to facts about aging research. Researching and treating diseases in the young-old constitutes a low-hanging fruit for medicine and pharmaceutical companies. This is in stark contrast to the complicated web of damages accumulated systemically, perpetuating the declining health of people aged over 80. The 85+ group have been historically ignored due to lack of research on aging itself. I refer to "aging itself" to mean the metabolic waste accumulation ultimately causing the systemic frailty syndrome seen in the old old.

A major problem is that aging has not historically been defined as a disease, warranting detailed scrutiny in order to constitute a target for medicine. The world is paying the price for it. It is still not known exactly what diversifies people aged 100+ on a molecular and cellular level, versus people dying of age-related diseases in their 80s. This is due to a significant lack of autopsies, quantifying the aging damage of the centenarians. Therefore it is not understood exactly how this age category succeed in avoiding lethal pathology for so long, and how their accumulated pathology might differ.

This is ultimately the only way forward to successfully get aging under control and truly change the late 80s mortality peak and prolong maximum human lifespan beyond 100. Currently the most common age of death in Sweden is 86 for men and 88 for women, for comparison the life expectancy is 80 and 83.5. From what we can deduce, risk avoidance, as well as avoidance of well known health issues like smoking and obesity, won't give much. These modifiable factors will only shift the life expectancy towards the most common age of death. The geriatric costs are staggering, we cannot afford more short-term thinking chasing low hanging fruits labelled diseases in the young-old. Quantifying the precise systemic tissue damages in the very old is paramount for developing concrete medical targets, targets composing the panel of upcoming therapies bringing aging under medical control.

Link: http://www.longevityreporter.org/blog/2015/9/8/anti-aging-old

Comments

He's fixated a bit on numbers, which is a poor idea. C'mon, it's 2015, name the enemies: glucosepane, senescent cells, mitochondrial dysfunction, immune system overloading, cell depletion, a signaling environment all shot to hell.

Most of the stuff he mentions that kills off the "young old" as he describes them are (with some exceptions) First World slow suicide methods involving sugar and LDL cholesterol.

Posted by: Slicer at September 17th, 2015 11:41 AM

If you aren't able to correct the genetic program that allows metabolic waste accumulation in cells after reproductive age, you will never impact that and other symptoms of "aging" be they "low fruit" and just excuses.

This is why it is such a waste of time, effort and resources to continue to further explore,describe, and define aging symptoms and variations ad nauseaum in the aged - without correcting their causes. The genetic mechanizes and related pathways that protect us in youth, are the same mechanizes that will eventually protect us from aging as continue to add years to our lives. Extended longevity is necessarily extended youth at sexual maturity.

Posted by: Durwood M. Dugger at September 21st, 2015 10:46 AM

"If you aren't able to correct the genetic program that allows metabolic waste accumulation in cells after reproductive age, you will never impact that and other symptoms of aging"

Nope. You only need to regularly repair the damage. No need to mess with genetic pathways.

"The genetic mechanizes and related pathways that protect us in youth, are the same mechanizes that will eventually protect us from aging as continue to add years to our lives."

Not at all. There are several kinds of damage that our body can't repair (for example, glucosepane), and many others that it repairs too slowly. And this is of no use when the repair machinery also becomes damaged (for example, stem cells).

Posted by: Antonio at September 22nd, 2015 4:00 AM

Antonio, It is undeniable that most if not all forms or repair including genetic repairs decline with or age after sexual maturity - and they do so with remarkable predictability across all races of humans which is proof they are indeed a genetic default process.

While you can address each repair process (many of which are characteristic of the various typical stages of aging) with some singular repair agent like the one you point out, it doesn't alter the genetic default aging process. Correcting one process or a 100 processes will have little impact on the aging process itself. Bottom line is that you end up with the necessity of 1000s or more of needed repair processes and their respective agents to have any significant impact on aging or longevity - if those agents are even determinable.

Aging is a cascade process. Interrupting one, a few or even many aspects has little to no impact on the cascade process that began decades earlier - unless you alter the cascade process at its point of initiation.

If you could interrupt the genetics of aging then you would conceivably keep the entire repair genetic process "master plan" - suspended at an optimum point, intact, stable, and in loop fashion. There would be no decline of the cellular repair system any more than there is in the avg. 18 year old. This would mean major metabolic repair processes as provided by our various immune systems would not decline with aging. Your example of glucosepane is an in product of the aging cascade. In a genetically young individual - this problem would never arise because the metabolic processes that cause it are eliminated before they start. No repair required for glucosepane - and many other post genetic cascade aging processes that are actually the result of aging past your genetic optimum.

Many of the diseases associated with our aged (and progressively failing) immune system that is progressively failing to respond correctly - would never begin. Diseases like immune system failure to identify cancer cells and or other genetic errors would be attacked and destroyed - as they are in our youth and not survive or initiate their own cascade of destruction. It would mean that the rate of stem cell production would not decline and genetic errors in stem cells would simply result in their destruction by the immune system - just as they are in our youth.

The piecemeal approach to treating the symptoms of aging may indeed relieve some symptoms temporarily (certainly the goal of the pharmaceutical industry) and of course that reduces the some related misery, but a non-systemic non-genetic approach has no mechanism to affect the over-all genetic default aging process and consequently it will have little impact of the systemic metabolic decline symptoms and diseases associated with aging.

This begs the credibility, the ethical and real intent of most anti-aging research/industry to date - which clearly has more to do with symptom treatment and medical/pharmacological product development - than it does dramatically slowing and extending life spans and or ending aging diseases in humans all together. Sorry, you can't have this both ways.

Posted by: Durwood M. Dugger at October 26th, 2017 1:23 PM

"Antonio, It is undeniable that most if not all forms or repair including genetic repairs decline with or age after sexual maturity - and they do so with remarkable predictability across all races of humans which is proof they are indeed a genetic default process."

No, it's no proof at all. They degenerate at the same rate because selective pressure for maintaining the repair mechanisms in good shape is the same for all of them. If some repair mechanism degenerated slower than the others, it would genetically drift to a worse mechanism.

"While you can address each repair process (many of which are characteristic of the various typical stages of aging) with some singular repair agent like the one you point out"

I didn't point out that. On the contrary, I said "you only need to regularly repair the damage". There is no need at all to mess with the body's repair processes.

"If you could interrupt the genetics of aging then you would conceivably keep the entire repair genetic process "master plan" - suspended at an optimum point, intact, stable, and in loop fashion."

The natural repair processes are HUGELY more complicated than the damage they repair, and they interact one with other in many complicated ways. And, to begin with, as I said, there are types of damage that they don't repair at all.

"There would be no decline of the cellular repair system any more than there is in the avg. 18 year old."

The 18 year old's repair systems also decline. There is nothing special at that age. Damage accumulates during all your life, some of it even in the womb.

"Your example of glucosepane is an in product of the aging cascade. In a genetically young individual - this problem would never arise because the metabolic processes that cause it are eliminated before they start."

The metabolic process that cause it is sugar transport in the blood, and you can't eliminate it or you will die. The same for other damages. Mutations are caused for example by cell reproduction. Eliminate cell reproduction and you will die. Mitochondrial damage is caused by breathing. Stop breathing and you will die.

Posted by: Antonio at October 26th, 2017 3:57 PM

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.