Superageing: a new physiological paradigm

The term superageing appeared in the scientific literature about a decade ago, to describe people over 80 who had superior mental abilities, including memory performance equal to a 50-year-old.

The term Superager has overtones best suited to the heroes of Marvel comics. I am an 89-year-old who can handle not only the concepts expressed in this article, but in September 2024 cycled from London to Brighton.

I have maintained optimal physical and mental capabilities for my age by following a lifestyle as recommended, eating sufficient to maintain the correct weight for my age and height, exercising to World Health Organisation requirements and avoiding smoking and excess alcohol among others. I am disease-free.

There is no magic here. When compared, for example, to a 50-year-old who has an unhealthy lifestyle, I'd be found to have superior function. However, compared to

an exercising 50-year-old, I would be functionally inferior.

This is because non-exercisers are on a different functional trajectory to me. That trajectory is almost certain to involve suffering from one of the 22 diseases linked to insufficient exercise and overeating. We need to ensure we're comparing like for like when making comparisons.

Exercise is integral for maintenance of function. Lifestyle is, in many cases, a deliberate choice. 

Age (time) is not a process 

Globally, adults now have an approximate lifespan of around 70 years. Since immortality is unknown in humans, it is safe to state that humans have inbuilt physiological processes that are designed to fail, resulting in death.

You can readily see these inbuilt processes at work in professional athletes. When they reach around 40 years old, their function has declined so that they cannot compete with 20-year-

olds. Note that the time (age) difference between a 20-year-old and a 40-year-old is immutable. It cannot be shortened, lengthened, accelerated, slowed or in any way manipulated.

Time is not responsible for the ageing process.

Time is not a process. It is not time (ageing) that is causing the physiological changes. It's these inbuilt regulatory processes that define physiological function, and these need time for their effects to manifest. 

It is possible that lifespan may increase but, again, that is not due to manipulating time but because of changes taking place in the regulatory processes. 

Complexity in physiological processes 

The physiological processes ushering the organism to death are not monolithic. There exists a mosaic of interacting processes in which the result of their integrated, co-ordinated actions is to drive down functional abilities.

In an age where physiological research is still based on the outdated concept that increased understanding of a single system will begin to unravel, the complexities of an integrated, coherently declining process affecting every system and potentially every cell in the body is unfortunate.

That model may be fine for disease, but it provides little comfort for those of us who wish to understand how function, while diminishing, is kept integrated and coherent so that function is held optimal for each reduced state in exercisers.  

Four categories of physiological regulation 

There are four main processes at play.

Category A regulatory processes consist of those processes that, while declining, cannot be modified or influenced. They continue their fixed downward trajectories irrespective of lifestyle. These can be exemplified by Maximum Heart Rate (MHR).

The trajectory of decrease can be reduced to a simple formula. MHR = 220 – age. That is it.

As time passes the regulatory processes in Category A will ensure decline irrespective of any known intervention.

In Category B, declining processes can be modified by exercise. They can only be modified not stopped.

Exercise will raise VO2max values, but VO2max will always be headed downwards. The increased VO2max values demonstrate that cardiovascular-related systems are delivering oxygen to the mitochondria as optimally as possible for the declining state.

Since VO2max is the gold standard for ameliorating all-cause mortality, any interventions that do not raise VO2max levels will be inadequate for the preservation of optimal function. Regulating multiple biomes without regulating cardiovascular integrity will be futile.

Category C processes are not programmed to functionally decrease over the lifespan. They can be positively influenced by exercise. For example, myonuclei retain their round shape in exercisers but become elongated in non-exercisers. They will retain these respective alterations throughout a lifetime.

Category D processes remain constant. These constant indices are commonly used for diagnostic purposes because changes in their values are excellent indicators for disease.

Blood indices were measured in a 91-year-old exercising woman whose blood was sampled over a 15-year time interval, from age 76 to 91.

These indices have not varied and are all within normal clinical ranges. Platelet count, Haemoglobin values, total white cell count, basophil count, haematocrit, red blood cell count, serum alkaline phosphatase, serum albumin, serum triglycerides, serum creatinine,

serum sodium and potassium. There are others, but these should suffice to show the stability of values in Category D.  

Superageing needs a different physiological paradigm 

Optimal function for age can be divided into those who are disease-free, those who maintain optimal function (maintained high VO2max values) despite the presence of a well-controlled disease (people with controlled disease have won Olympic gold rowing medals and have played premier league football) and those who, unlike the above, have suboptimal function because oxygen delivery to mitochondria has been compromised (low VO2max values), whatever the underlying reason.

Of these categories, the disease-free people are the most intriguing. The present approaches of physiological studies are inadequate to properly address this phenomenon.

A new paradigm in physiological textbook writing, teaching and research needs to be found to directly address the fact that human physiology is the study of failing functions, integrated in a manner that allows diminishing but optimal function, age for age, throughout a lifetime provided lifestyle includes exercise. The processes taking place in

non-exercisers are largely pathological, not physiological.

Based on article by Dr Norman Lazarus published in Physiology News, Spring 2025.