The Old are Becoming Functionally Younger

Today's research materials cover one of a number of studies to suggest that older people are becoming functionally younger over time, comparing the capabilities of age-matched cohorts of old people in past decades with old people of the same age today. Being 70 or 80 in 1990 was accompanied by greater loss of physical capabilities, such as walking speed or grip strength, than is the case at those ages today. This is what one would expect given the slow upward trend in life expectancy that has continued year after year for more than a century now, driven by a shifting combination of better lifestyle choices, greater control over medical issues throughout life, and slow improvements in treating age-related disease.

It is interesting to see just how much has been achieved without undertaking direct efforts to target the mechanisms of aging. While the reasons for a lesser burden of frailty and mortality in late life have changed over time, from a reduction in the burden of infectious disease across the 20th century to a lessening of cardiovascular disease over the last few decades, the theme remains an incidental reduction in the level of accumulated damage and dysfunction at a given age. Now that we are moving into an era in which the research and development community is actively and deliberately targeting underlying causes of aging, we might expect to see a considerable increase in the upward trend of vigor, health, and longevity in old age.

Older people have become younger: physical and cognitive function have improved meaningfully in 30 years

Among men and women between the ages of 75 and 80, muscle strength, walking speed, reaction speed, verbal fluency, reasoning and working memory are nowadays significantly better than they were in people at the same age born earlier. In lung function tests, however, differences between cohorts were not observed. "The cohort of 75- and 80-year-olds born later has grown up and lived in a different world than did their counterparts born three decades ago. There have been many favourable changes. These include better nutrition and hygiene, improvements in health care and the school system, better accessibility to education and improved working life."

The results suggest that increased life expectancy is accompanied by an increased number of years lived with good functional ability in later life. The observation can be explained by slower rate-of-change with increasing age, a higher lifetime maximum in physical performance, or a combination of the two. "The results suggest that our understanding of older age is old-fashioned. From an aging researcher's point of view, more years are added to midlife, and not so much to the utmost end of life. Increased life expectancy provides us with more non-disabled years, but at the same time, the last years of life comes at higher and higher ages, increasing the need for care. Among the ageing population, two simultaneous changes are happening: continuation of healthy years to higher ages and an increased number of very old people who need external care."

Cohort differences in maximal physical performance: a comparison of 75- and 80-year-old men and women born 28 years apart

Whether increased life expectancy is accompanied by increased functional capacity in older people at specific ages is unclear. We compared similar validated measures of maximal physical performance in two population-based older cohorts born and assessed 28 years apart. Participants in the first cohort were born in 1910 and 1914 and were assessed at age 75 and 80 years, respectively (N=500, participation rate 77%). Participants in the second cohort were born in 1938 or 1939 and 1942 or 1943 and were assessed at age 75 and 80 years, respectively (N=726, participation rate 40%). Maximal walking speed, maximal isometric grip strength and knee extension strength, lung function measurements; forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were assessed. Data on non-participation were systematically collected.

Walking speed was on average 0.2-0.4 m/s faster in the later than earlier cohort. In grip strength, the improvements were 5-25%, and in knee extension strength 20-47%. In FVC, the improvements were 14-21% and in FEV1 0-14%. The later cohort showed markedly and meaningfully higher results in the maximal functional capacity tests, suggesting that currently 75- and 80-year old people are living to older ages nowadays with better physical functioning.

Comments

Only negative nowadays is number of overweight people. But, mostly, it's on them.

I hope to still be jogging on my treadmill in my 70's and awesome if it could happen in my 80's:)

Posted by: Robert at September 28th, 2020 4:33 PM

If senolytics are even half as effective in humans as in animal models this trend can only accelerate. Perhaps the best way to accelerate senolytic research would be either or both of:

A. Some demonstration of hair growth / hair restoration.
B. Some demonstration of reversing erectile dysfunction.

As far as I can tell, those are the two areas of "anti aging" that really pull in the bucks from average people.

Posted by: nobody at September 28th, 2020 5:40 PM

Very interesting,
can we make some comparison to say that the 80ys are functinally equivalent to say 75 or 78 ? The 80s are the new 78s ?

@nobody
point A was pestering me since my early 20s. The last 10 years it has slowly progressed coupled with graying. Annoys me, but I can live with that as long as i don't get worse with my tendons, backpain, eyesight , hearing, sense of smell , muscle and basically the whole misery set..

Point B kinda has a solution with the blue pill. Not everybody responds well, but this is kinda solved problem if you don't have other big issues.

But of course if I could dial the clock on those I wouldn't mind (for B having a drive of a teenager would be too much, though)

Posted by: cuberat at September 28th, 2020 5:54 PM

The question is how much of an improvement could senolytic therapies bring for those two cohorts?

Posted by: cuberat at September 28th, 2020 6:19 PM

@nobody
'If senolytics are even half as effective in humans as in animal models this trend can only accelerate.'

So far there is no evidence they are.

Posted by: Mark at September 29th, 2020 9:00 AM

@Mark

"'If senolytics are even half as effective in humans as in animal models this trend can only accelerate.'

So far there is no evidence they are."

Yes but so far there is no real evidence that senolytics are not as effective in humans as in animal models, as large scale testing has not taken place yet.

The only large scale testing in humans (Unity's trial) involved only local knee injection, and subjective end points (patients perception of knee pain) both of which might have prevented a postitive result. In addtion the small moecule drug used by Unity targeted different cell survival pathways to those targeted by Dasatinib + Quercetin. I supsect local injection only may have been the culprit, rather than ineffectiveness, but in any study with subjective endpoints the placebo effect can obscure real results.

I would love to see the result of a larger D+Q trial against 6 minute walk times (an objective endpoint) in pulmonary fibrosis. I don't know if the Mayo clinic or whoever carried out the small first trial have the funding to repeat it with a larger number of participants?

Posted by: jimofoz at September 29th, 2020 11:32 AM

I can't wrap my head around the fact that senolytics can make much of a difference given that senolytic compounds exist in nature.
We would have seen *something* by now. You know, get one million monkeys to bang their paws on a typewriter for one million years and one of them will have re-written the Divine Comedy.
My feelings are the same about plasmapheresis etc.
I am starting to believe that only reprogramming and gene editing (perhaps to rid the system of damage) will lead to effective rejuvenation, by which I mean life extension of more than a decade, give or take.

Posted by: Barbara T. at September 29th, 2020 4:32 PM

@Barbara - given that fungi produce antibiotics, how come no one ever ate a mouldy piece of bread and noticed that it cured their infected wound?

Probably dosage. To get enough of a fisetin dose you would have to pounds of strawberries, and even then you couldn't absorb it. Azithromycin - I'm not sure anyone has run lifespan studies in mice yet.

Posted by: jimofoz at September 29th, 2020 8:38 PM

@jimofoz: not sure about that, but cattle owners had a lower smallpox mortality even before Jenner discovered variolation. So I don't think examples from the past apply here, especially if they relate to infectious diseases rather than metabolism and / or cellular mechanics.
Having said that, I *feel* that senolytics and the likes won't help much, but my feelings, like everybody else's to be honest, are meaningless. The only way to find out is through properly run and properly designed trials. This means measuring mortality in the elderly, rather than some disease marker which may well have no impact on longevity.

Posted by: Barbara T. at September 29th, 2020 9:32 PM

@Barbara T.
It
You might be right but there were so many examples of simple discoveries that were just sitting there unnoticeable just in front of our eyes.

For example, scurvy was killing sailors for centuries. (There's a recent article about this) And there were anecdotal evidence that lemons sometimes can cure it. Yet until the discovery of the vitamins it was a mystery.

Basically, if we are lucky we might stubble on something like antibiotics (Senolytics look promising) that with simple treatments can solve the incurable death sentence of the yesteryear.

If there's no such luck we will have solve every single pathway, replace the falling cells with genetically edited lines and do other things.

For the moment, I would be content if we increase the healthspan even at the cost of everybody drops dead at 80-90

Posted by: Cuberat at September 29th, 2020 11:23 PM

@Barbara T - Hopefully the annoymous donar who gave 40 million so that the metformin trial could go ahead will soon see that senolytics are a better bet and will sponsor half of a trial of D+Q (or Oisin's or some other improved senolytic) in 75 year olds (or some age) to look for lifespan and healthspan effects. Maybe this will only happed after promising stage 1-2 results show efficiency?

My biggest worry is that senescent cells are more homognous in mice than in humans, and so D+Q or Oisin's P16 targeting suicide gene therapy will have more effect in mice than in humans. It would be a big help/reassurance if different types of senescent cells had been better studied and characterised.

On the other hand we know that all 7/9 categories of damage need to be at least partially removed to achieve any large effect getting a lot of people to longevity escape velocity, not just the under fifty fives or those that have not yet acquired a medical condition. I'd be interested in seeing the combination of senolytics plus at least one or two other treatments such as Revel's and Underdogs.

Posted by: jimofoz at September 30th, 2020 2:52 AM

Remember that (lab) mice have ridiculously long telomeres and therefore always have spare divisions to replace (dysfunctional) cells deleted via senolytics. All you have to do is remove the bad cells and their malign influence on the surroundings and this allows healthier cells to do their work. It is highly questionable that this can be read across to humans; all mice trials are questionable to my mind.

I agree with what others have said about needing to hit multiple treatment pathways at once. For example in humans a senolytic round followed by stem cell replacement would be a much safer bet than senolytics alone to extend health and lifespan.

Posted by: Mark at September 30th, 2020 4:49 AM

@jimofoz at a 160 mg per kilogram of strawberries, at a dose of 25mg/kg of body weight for single dose (minimum working for male) and 100 kg of weight you would need actually at least 15,6 of kilograms (32 pounds?) of strawberries, eaten at once... All the life length enhancement that lower doses of fisetin provide, was counted as a part of a general life span increase that took place in the last century... along with the many other substances that lengthen lifespan at least in some people, like metformin, silibinin, etc.

Posted by: SilverSeeker at September 30th, 2020 9:02 AM

@SilverSeeker
if i manage to eat 16 pounds (not even kgs) strawberries i will get an effective CR due to the diarrhea :)

Posted by: cuberat at September 30th, 2020 2:50 PM

@Cuberat: hahaha! :-)

Posted by: Barbara T. at September 30th, 2020 5:48 PM

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