OT? Big Data on life span

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This is what I call Big Data: > 60,000 people, 15 years of follow-up, 7,000 plasma proteins. Of course, all results are averages and individuals will differ. But the results are highly reliable.

There are several authors, including the Global Neurodegeneration Proteomics Consortium (GNPC) which itself has several authors.

https://www.nature.com/articles/s41591-026-04446-y

This may have Macroeconomic impact because lifestyle can improve our health and longevity. Longer lives mean more medical costs which can dramatically increase government deficits.

The key observation from this study is that different systems in our body can age at different rates. The proteins made by these systems tell the story. The more systems stay young, the better off we will be. The more systems begin to age, the more our overall health will suffer.

The study looked at neuronal (brain nerves), immune, glial (supporting brain cells for the neurons), endocrine (hormones, including insulin), epithelial (skin and the lining of blood vessels and lung, digestive tract and other hollow organ linings) and musculoskeletal origins. That’s a lot of different types of cells that can be aging at different rates.

Finally, they developed a “polycellular aging risk score.” We may get sick one organ at a time but if one system fails completely or several at the same time our entire body will die - even if some systems are still OK.

There are many ways to analyze system aging. This study used proteins in plasma (the science of “proteomics”) which is relatively non-invasive and inexpensive.

The study observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up.

For each cell type and individual, they calculated an ‘age gap.’ They took the average from the entire 60,000 person group. Then they compared each individual to the average for each protein. If the individual had a more aged protein they assigned it a (+). If the individual had a younger protein they assigned it a (-).

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The Global Neurodegeneration Proteomics Consortium (GNPC) is a large-scale international neurodegenerative disease plasma proteomics resource comprising multiple subcohorts. They already had this set up so the analysis was largely based on these participants, some of whom are healthy and others are sick. They used a separate research study, UKB, added to the GNPC.

They used the healthy people to establish a normal baseline which they compared everyone else to. Across all healthy individuals in the GNPC cohort, they found 35.4% had no extreme cellular age gaps and 24.4% had accelerated aging in a single cell type, while 1.5% of the population experienced widespread acceleration across 10 or more cell types.

Notably, cellular age gaps demonstrated associations with modifiable risk factors in the UKB cohort. Among individuals with concurrent smoking and obesity (n = 1,046), they observed widespread increase in biological age across multiple cell types, while individuals with a healthy lifestyle (n = 1,044) defined as never smoking, no alcohol consumption, body mass index (BMI) lower than 25 without enlarged waist circumference, sufficient sleep (≥7 h nightly) and regular exercise (≥5 days weekly), showed overall younger cellular ages.

This subset represents approximately 2.3% to 4.6% of the population studied. A landmark study published in Mayo Clinic Proceedings tracked four primary healthy habits using NHANES data: a good diet, moderate exercise, a normal body fat percentage, and not smoking. Only 2.7% of American adults qualified across all four categories - and they didn’t even include alcohol!

This practical take-away won’t surprise anyone on METAR. How many of us qualify on all counts? I sure don’t. My BMI is over 25. However, a separate study showed that BMI between 25 and 30 actually results in better longevity for people over age 60 (compared with < 25 and > 30).

The article is long and complicated. They correlate specific protein aging types with specific chronic diseases. The differences between the least and most aged are very significant and actually scary.

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I was amazed to see that the strongest association with mortality (death) was from muscle cells. That’s pretty amazing considering how easy it is to improve muscle health with simple physical training.

Skeletal myocyte (muscle) aging showed the strongest association with mortality, followed by neurons (brain cells), fibroblasts (collagen-building cells), alveolar type 2 cells (lung oxygen exchangers) and myeloid lineage cells (which make red and white blood cells); implicating musculoskeletal, cognitive, pulmonary and immune maintenance in longevity.

Weak muscles lead to frailty and often to falls. Dementia leads to death in many. Lungs are essential to life. Immune system weakness can lead to vulnerability to infection.

This last chart shows life and death. No fooling around! Those falling red lines mean that people are dying.

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This is a really important research study with a huge amount of effort and data. It shows that a non-invasive blood test can accurately determine which physical system is aging more rapidly. This is actionable data that can help doctors recommend lifestyle changes to vulnerable patients, even ones who look healthy.

Meanwhile, I’m going to turn on a video and do a Zumba class.

Wendy

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Thanks @WendyBG …looks like a good read. I’ve put in the sweat equity to be able to indulge myself with a tuchis in the chair concentration level for a read…when I’ve done the yard chores. Heavy training session yesterday. Meaningful early morning Z2/MAF/ASCVD mitigation/mitochondrial enhancing 45 minutes on the treadmill (home) then a top up on my upper body (back and shoulders at the gym) today.

I won’t be taking too much notice of a study showing better outcomes from being overweight, however. These contrarian publications crop up periodically…and fade away. Not before they’ve spawned a lot of jibber jabber in the various media outlets. I recall one such a decade or so ago. Hugely popular with the HAES and Fat Acceptance movement at the time. Roundly debunked by peer review, however…as the study authors had culled their statistics from databases that linked mortality (death) with weight in the 6 weeks or so prior. Totally disregarding the actual causes of death…especially whether or not said death took account of the many wasting diseases that can reduce the sufferers to literal skin and bone purely as a consequence of the disease itself. My in-laws would be the perfect examples. Both comfortably padded for as long as I knew them…until the final few weeks before their deaths. FIL from cancer of the oesophagus and MIL from a brain stem glioma.

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Isn’t that the point? The excess material keeps the engine running a bit longer…

I wouldn’t phrase it as better… but longer to suffer at the end for non-catastrophic events since there is a metabolic reserve.

My uncle is wasting away currently of Pancreatic Cancer. His prognosis is CONSIDERABLY better at the moment since he has/had significant reserves. As you may ascertain, his condition prior to the nastiness would have been helped if less “mass” was available to temper healthy processes elsewhere in his system.

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Nope. As far as the study(s) go, there was no discussion beyond mortality (death) as it occurred at any given age/weight…but no breakdown on causes of death, or that the relationship between low body weight and death might be due to a disease with wasting as a symptom (as opposed to death from opioid overdose or road traffic accident etc.etc)

For sure, having witnessed the last few weeks of my in-laws suffering…and coma towards the end … I seriously doubt anyone interested in applying principles of longevity see lingering for longer in a moribund state as a plus.

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@VeeEnn my personal observation during recovery from multiple surgeries is that having extra resources (fat) helped me rebound and recover when I couldn’t eat well.

I asked Gemini about your statement. The answer was more nuanced than you presented it.

From Gemini:
Your acquaintance’s critique highlights a massive, ongoing debate in epidemiology regarding reverse causality, but claiming the phenomenon has been “roundly debunked” oversimplifies a deeply nuanced scientific reality.

1. The Core Critique: Reverse Causality

Your acquaintance is right about the mechanism of the primary scientific criticism, though inaccurate regarding the specific “6 weeks” detail (most large cohort studies track people over years or decades, not weeks).

…snip more comments …

The Reality: The “Obesity Paradox” in the Elderly and Critically Ill

While the protective effect of a 25–30 BMI largely disappears for healthy, young, non-smoking adults when you control for reverse causality, it does not entirely disappear for the elderly or the acutely ill. This clinical reality is heavily studied under the term The Obesity Paradox.

The reality of your personal observation—that carrying extra metabolic reserves improved your survival during surgical complications—is highly supported by clinical data.

Why Extra Weight Can Be Protective in Medical Crises

  • Metabolic Reserves for Catabolic Stress: Major surgery, severe infections (like sepsis), and prolonged trauma plunge the body into a hyper-metabolic, highly inflammatory state. The body begins rapidly breaking down its own tissues for energy (catabolism). A patient with zero fat or muscle reserves can quickly deplete their energy stores, leading to organ failure. Having a metabolic “buffer” provides the caloric fuel needed to survive weeks of critical illness.

  • The Sarcopenia Factor in the Elderly: In older adults, BMI is an imperfect metric. An elderly person with a “normal” BMI of 22 might actually be suffering from sarcopenia (severe muscle wasting) combined with a high proportion of internal visceral fat. Conversely, an older person with a BMI of 27 may have preserved lean muscle tissue alongside a protective layer of subcutaneous fat.

  • Cytokine Protection: Some adipose (fat) tissue can produce soluble cytokine receptors that bind to and neutralize harmful tumor necrosis factor-alpha (TNF-$\alpha$), potentially dampening the overwhelming, destructive inflammatory responses seen in acute illness or surgical complications.

The Takeaway

The study wasn’t “debunked” so much as it was properly contextualized. For a healthy 30-year-old, carrying excess weight increases long-term cardiovascular and metabolic risks. But for an older adult facing the physical stresses of aging, acute hospitalization, or major surgery, carrying a modest physical reserve (a BMI in the 25–30 range) functions exactly as you perceived it: a vital engine of resilience and a protective insurance policy against severe illness. [end Gemini]

You may reject anything from Gemini. You may claim that prolonging life during a terminal illness (like pancreatic cancer) isn’t worth it.

But you ignored my specific situation – when a patient is knocked down by a health crisis and can recover with sufficient resources but may die without them.

The original study was of all-cause mortality. They analyzed the raw numbers without considering the cause of death. There’s a good reason that elderly people with a healthy “bank account” of fat live longer than the very lean. Whether they survive to recover their health or die when the fat is depleted, they live longer.

Wendy

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I am going to Costco today and buying a bag of chips.

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Ahh…the beauty of AI. Even the nuances lack nuance.

I was referring to one or two specific studies that were glommed onto by the Health and Science writers in the popular press maybe a decade or so back…with the sort of banner headlines that proclaimed “Study shows overweight is healthier”. You actually mentioned “a” study (singular)…which I inferred to be one along these lines … rather than the confluence of evidence with its caveats such as you’d likely find on an AI bamboozle tool.

Since I actually did expect some to defer to an AI opinion, I already took a sneak peek at what would likely crop up so I’m not surprised by what you found.

Whilst it’s a plausible-sounding argument…especially when crafted by AI…that having spare energy reserves at a time of acute illness/injury/surgery/hungar strike, it’s really a bit of a stretch to infer this actually means being overweight/overfat has advantages over not fat (normal BMI) sufficient to cancel out the negative consequences of, say, excess visceral fat, hyperglycaemia, hyperinsulinaemia etc. that very frequently occur with advancing adiposity.

FWIW, my BMI currently is well below the 25 cutoff…toggling around 135lbs at a height just shy of 5’6"…there’s plenty of accumulated energy stores to see me through tough times.

Caveat: no AI input in this post, so all opinions, dodgy inference drawing, pore speling, and misuse of the Oxford comma are all my own.

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I found the AI response quite educational. At different stages in life our bodily requirements vary.

The Captain

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Now that I’m thinking back on the study I mentioned…which may be the one you’re thinking of: all cause mortality and BMI at time of death (was quite a discussion on it back on the H&N Board at the time)…one thing that sticks in my mind, not to mention my craw, is one of the points the authors raised in the discussion. Among the tentative explanations (which omitted the death from wasting diseases confounder) was the suggestion that maybe the index of suspicion for the many diseases commonly associated with metabolic dysfunction and random stuff downstream of excess body weight (and by implication body fat) was higher in the overweight than normal, “healthy” weighted individuals and that they got a second look and maybe earlier/more targeted interventions. I didn’t really buy into that back the, seeing that I was being roundly reasurred that any out of range biomarkers were well compensated for by my righteous lifestyle and excellent physical shape. EXACTLY the situation that the authors were describing.

Usual caveat on non use of AI…not least because it takes too long to think up a totally non biased way to ask any question…and get an ultimately misleading answer if ones bias is too obvious. See, Gemini fathomed that you wanted confirmation that being overweight gave you a reserve of stores necessary to recover from surgery. It presumably didn’t know that one doesn’t need to be overweight for this situation to occur. Too lean wouldn’t be optimal, of course but, for sure, a BMI slap bang in the middle of the healthy range provides for a more than adequate reserve without the negatives.

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Here it is. The study…the one…the only one…I referred to initially and since!! I knew the first author was a woman and name began with an F…

Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis - PubMed Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis - PubMed

Early morning waking can be a memory jogger (perhaps AI overview will reassure me that disrupted sleep is good for slowing cognitive decline and memory loss if I ask the right questions)

Full disclosure…it wasn’t memory. In response to the upstream comment on AI responses being interesting, I asked Google “Why does AI say overweight is protective in medical crises?”. Obesity Paradox and metabolic reserves of the overweight vs underweight and frail were mentioned along with other suggestions …different ones each time, oddly enough … each time I went back to ask it the same question. Presumably trying to curry favour, the brown noser !!

Anyways, the important thing to me isn’t so much the opinion AI is trying to foist on me, but rather how did it form the opinion in the first place so, treating it like a glorified retrieval service with ideas above it’s station, I set to accessing the sources it scanned. That’s how I found the study…the only study I had in mind in my first comment upstream.

It’s behind the usual paywall and I guess that’s my advantage over AI…back then, I had ready access to Harvard’s medical library via husband’s PIN. Not only did I have a chance to study the full primary document, but also the subsequent letters challenging the hypothesis with the valid reasons of poor methodology, BMI as a questionable metric etc. Per my link, there’s no abstract for any of these examples of peer review for any AI platform. So there, Gemini…don’t argue the toss on a topic too forcefully when you’re the one short on facts.

Edit: I thought it was my imagination that my AI overview was trying all these different ways to force its opinion on me and on one occasion it did come up with an idea it dredged from somewhere that might have a chance. That the chronic inflammation caused by excessive bodyfat maybe, possibly, perhaps, peut etre actually primes the immune system to be more readily able to initiate a response to sudden illness /injury etc. I didn’t get around to accessing the source of this, unfortunately. It doesn’t seem to have been an idea that folk have tapped into. I’ll still stick with my low hs-CRP and my not fat, not frail body, I think.

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