A Consensus Definition of Aging Would be Useful Now, But is Unlikely to Arrive Soon Enough to Help

Aging is poorly defined as anything other than an outcome, as is pointed out in today's open access paper. Aging is the rise in mortality risk due to intrinsic causes over time, a definition that is hard to argue with, but that provides next to no insight. There are more complicated and detailed definitions, but near all are all quite similar in being a catalog of symptoms rather than a catalog of processes. The SENS view of aging, on the other hand, is in fact a list of causative processes, but is by no means widely agreed upon, nor expected to remain unchanged by later data.

Definitions of aging that are in effect a taxonomy, in the sense that we put these humans into the "old" bucket because they exhibit measurable symptoms A through Z, are really not helpful at all when it comes to the development of therapies to treat aging. One needs to know what to target. What processes must be interrupted? What damage must be repaired? This is the entire point of the SENS view of aging: that we need this description of aging as a set of processes, rather than as a set of symptoms, in order to even start building effective rejuvenation therapies.

Sadly, validating a consensus definition of aging is only going to be achieved via the production of working rejuvenation therapies. If one repairs a form of damage and that actually works to produce rejuvenation, then that is supportive of definitions of aging that include that specific form of damage. It seems likely to me that there will be active debate over the causes of aging all the way through the process of producing a first generation package of good-enough rejuvenation therapies that adds decades to healthy life spans. That active debate will take place alongside a great deal of wasted research and development effort, as people attempt to validate incorrect approaches.

The SENS view of aging is very important, not just because its conclusions as to areas of study and forms of therapy seem likely to be the best way forward to practical human rejuvenation, but also because, philosophically, everyone else should stop building taxonomies of aging and start thinking about causes and processes of aging. It will be a messy process all the way from here to the goal of physical immortality and medical control of aging, but it seems that there could be a lot less wasted effort along the way than is presently the case. Incidentally, the paper noted here starts off well, and is an interesting read, but then falls into the pit of suggesting that aging is an intrinsic property of life, and thus not amenable to effective treatment.

An essay on the nominal vs. real definitions of aging

Several recent publications, including the one entitled "What if there is no such thing as aging?", have brought out an astonishing trend: the mere existence of biological aging is being questioned. The title reiterates the famous proposition "There is no such thing as aging and cancer is not related to it", and the paper suggests that the same is relevant to the other age-associated conditions: "...we are not studying a single biological phenomenon, but an assortment of loosely related processes that we find convenient to lump together"; ultimately, "... the concept of aging does not reflect any underlying biological reality".

Being intentionally provocative, the paper does however reflect the trend, which is developing, paradoxically, in parallel with the increasing prevalence of aged people in the world and with the recently emerged discipline called "geroscience". According to the geroscience agenda, the best way to combat the most prevalent age-associated conditions, such as atherosclerosis, cancer, type II diabetes, and neurodegeneration, is to target their common risk factor rather than each of the conditions specifically. The common risk factor is aging.

Apart of that the very practice of piling up of newly invented scientific disciplines and respective terms is questionable, a problem with the geroscience agenda relates to the feasibility of evaluating the benefits of its implementation. The benefits of targeting of a disease may be evaluated, based on its commonly accepted definition (diagnostic criteria), as a decrease in the incidence of cases recognized according to this definition. Can we decrease the incidence of aging otherwise than by making people dead before they get old? Any answer to this question depends on the criteria used to distinguish (i) aging from all the rest that may occur to living bodies and (ii) living bodies from all other kinds of bodies, in other words, on the definition of (biological) aging. The lack of consensus on the definition of aging is long recognized and has recently been highlighted by asking several basic questions about aging to recognized authorities in aging research. Answers to each of the questions differed up to antipodal extremes.

Based on several scores of definitions found in the most highly cited (that is the most representative and influential) papers on aging, the following features commonly used to define aging have been distinguished: (1) structural damage, (2) functional decline, (3) depletion‚ÄČof a reserve required to compensate for the decline, (4) typical phenotypic changes or their cause, and (5) increasing probability of death. Noteworthy, these characteristics are not really five definitions of aging, but rather five defining features of aging. This the above inventory to the kind of definitions that in philosophy of science is known as "nominal" and is opposed to "real"

By its nominal definition, water is a colorless and odorless liquid having defined specific gravity, viscosity etc. By its real definition, water is a compound comprised of two hydrogen atoms and one oxygen atom connected in a certain order. Noteworthy, the real definition is senseless for people ignorant of atoms. Likewise, the nominal definition of aging as a set of observable features should be supplemented, if not replaced, with its real definition. The latter is suggested here to imply that aging is the product of chemical interactions between the rapidly turning-over free metabolites and the slowly turning-over metabolites incorporated in macromolecules involved in metabolic control.

The phenomenon defined in this way emerged concomitantly with metabolic pathways controlled by enzymes coded for by information-storing macromolecules and is inevitable wherever such conditions coincide. Aging research, thus, is concerned with the elucidation of the pathways and mechanisms that link aging defined as above to its hallmarks and manifestations, including those comprised by its nominal definitions. Esoteric as it may seem, defining aging is important for deciding whether aging is what should be declared as the target of interventions aimed at increasing human life and health spans.

Comments

"A Consensus Definition of Aging Would be Useful Now, But is Unlikely to Arrive Soon Enough to Help" - certainly not from the Doomer who wrote this paper lol

Let's just get on with testing approaches and we will find out if they are right or wrong. I can guarantee the outcome for us all if we opt to do nothing...

Posted by: Steve at June 14th, 2021 7:26 PM

Even if aging was an intrinsic and universal property of life it still doesn't mean that it cannot be slowed down or even reversed. If we look at our society we are actively modifying what is biologically natural for our bodies. Which is to be in a constant state of undernourishment and to procreate as fast and as much as possible.

We are quite far from being natural and we even use prosthetics to replace part of our bodies with "machines", albeit quite crude ones.

And another anti strawman argument is that there are species that in essence don't age.

And a side note. If we were to magically stop aging it doesn't mean we will live forever. Just much longer than today but probably not of us would for in 10 thousand years from various freak accidents , suicide, homicide and such

Posted by: Cuberat at June 14th, 2021 7:43 PM

Consensus on definition of AGEing is important.
AGEing is disease, abnormality, disorder. First define what is Normal. Being Normal means to be free from any disease and being biologically , physiologically young - functioning as a young person. Any deviation from this Normal state is Abnormality = AGEing. This Abnormality=AGEing can be manifested as signs and symptoms ( graying hair, wrinkles, weakness) and on microscopic level as processes of damage to molecules and accumulation of garbage that naturally can not be cleared.
It is also important to have a consensus on measuring AGEing and Rejuvenation, so that therapies in various countries can be compared with each other. By how many percent were you rejuvenated? And how many years you are expected to stay alive without additional treatment. Predicting individual life expectancy.

Posted by: Nicholas D. at June 14th, 2021 8:29 PM

@Steve... Very much agreed!

Posted by: matt at June 14th, 2021 8:58 PM

Aging is the incremental loss of resilience ultimately resulting in death.

Posted by: Lee at June 15th, 2021 9:01 AM

IMO, human life consists of predictable, genetically programmed, but environmentally modulated stages. In my recent essay on using 'anti-aging'-derived technology to massively upgrade the human herd, and lacking guidance of studied experts, human life was divided into five stages as quoted here:

"Phases of Natural Human Life: Age-related biological changes are complex and interactive. A search reveals several life-phase categorizations based upon measurements of chemistry, psychology, physiology, and physical, social, and/or cognitive function. Rapid changes and cognitive immaturity in early decades transition to relatively high-function young adulthood, then to measurable but minor physical impairment complimented by cognitive maturity, then to obvious physical degeneration but seasoned judgement, and then to increasingly profound and chronic morbidities, ending with death. Herein, natural life phases (which significantly overlap, individually vary by perhaps +/-20%, and are influenced by circumstances, lifestyle and medical interventions) are quintiled, as follows:

Formative: a phase of rapid change, from conception, through childhood and adolescence. Typical chronage: 0-17 years.

Reproductive Adulthood: a phase of peak overall physical capability (including reproduction). Typical chronage: 18-35 years.

Post-Reproductive Adulthood: a phase of child rearing and high productivity, characterized by increasingly noticeable but tolerable senescence. Typical chronage: 36-53 years.

Ambulatory Elderhood: a phase of reduced physical fitness and resilience, as well as emerging chronic diseases, but also seasoned guidance of younger community members. Typical chronage: 54-71 years.

Geriatric Elderhood: The high-senescence phase of natural life, defined by fading contribution to the community, one or more advanced physical and cognitive disabilities, then death. Typical chronage: >71 years.

Phases can be further subdivided (especially 'formative'), but the above provides adequately explicit and compact definitions of human bioage progression for our purposes."

The ambiguity surrounding the definition of 'age' and 'aging' was dealt with as follows:

"Age (and aging): a term referring to various chronological and biological measures. It is ambiguous to the point of impeding precise communication. New terminology follows.

Bioage (short word for 'biological age'; and bioaging - the process of reaching a bioage): the species-average chronage associated with the found phenotype of a tissue, organ or organism. Alternately stated, bioage is the average senescent state (which is typically somewhat non-uniform within a multicellular sample) of a tissue or organism, expressed as the chronage at which the found state is normally observed. Bioage is determined in various ways by amalgamating oft-overlapping circumstantial and lifestyle-mediated biomarkers that change predictably with time, including gross, microscopic and molecular phenotypes, e.g. (respectively), gait speed, stem cell exhaustion and epigenetic alterations. Among other biomarkers are grip strength and cognitive levels, telomere lengths, skin elasticity, genetic variants, disease and congenital covariants, microbiome, proteome and metabolome compositions, protein-sugar crosslinking, gestational environment and history, senescent cell density, visual appearance, extraneous extra- and intracellular matter, etc. There is a growing industry in measurement of bioage, using aging 'clocks' that compare biomarkers to the species average to arrive at a chronometric figure of bioage. For single-cell animals, the equivalent of bioage is 'replicative age'.

Chronage: For an organism, the amount of time since embryogenesis (for humans, time since birth, plus approximately 280 days). For a cell, the amount of time since differentiation.

Damnage: incremental bioaging caused by accumulated damage not due to genetically programmed degenerative factors. Damnage can result from stochastic, circumstantial, or lifestyle-mediated sources, e.g. (respectively), originating in necessary metabolism, cosmic radiation, or unhealthy dietary choices."

I would love to hear commentary on these definitions, which were found to be essential for clear communication in the essay, I am not married to these definitions, but they were better than what I found elsewhere.

Posted by: Walter Harvey Crompton at June 23rd, 2021 11:37 PM

If interested, the essay referenced in the previous post is titled "Fostering Better Humans Through Bioaging Deceleration in the Formative Phase of Natural Life". If this subject interests you, let's establish collaborative relationships to advance this approach. As it stands, humanity does not appear capable of safely dealing with current and near-horizon existential threats of our own creation, and a leap in cognitive capacity and longevity is necessary. It appears that slowing the rate of biological aging early in life promises a safe, inexpensive solution to this dilemma.

Posted by: Walter Harvey Crompton at June 23rd, 2021 11:51 PM
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