These are all fair points. I think it’s fair to say the older one is - the amount of theoretical disability-adjusted life years (DALYs) left is likely lower. I can’t imagine the urgency one can feel with remaining life expectancy, functional status and quality of life. Generally, people have a bias towards interventionism in these types of situations that should be evaluated in depth because interventionism in the context of treatment complexity tends to cause harm more often than we expect and many people do not recognize the limitations of evidence base in interpreting the medical literature.
Let me further explain my risk management approach when it comes to these uncertainties because it vastly changes the risk-reward equation when we think about cumulative tail risks instead of traditional risk management approaches that rarely address tail risks (most of the time these are ignored despite sizable impact).
When we cite statistics here about “healthy people”, it’s not from people using multiple drugs. The vast majority of “healthy” people aren’t under polypharmacy. Not to mention older “healthy” people here can have different physiology especially when it comes to possible “inappropriate polypharmacy”. And geriatricians are extremely few in numbers relative to the geriatric population that can even be qualified to address these medical management issues at an expert level.
Why do we care about polypharmacy? “Inappropriate polypharmacy” contributes to roughly 100,000 deaths per year and that’s an underestimate IMO. Insurance companies increasingly recognize it and pay for medication review for prevention because it’s very high impact.
It’s not as high as heart disease, but it’s on par with the top 5 or so. It’s probably higher than heart disease when you include optimal treatment, prevention strategies, and low risk experimental therapies. Note that the cause of death is usually whatever we write on it as the best guess. Nobody knows for sure even with path doing a biopsy and we don’t list all the contributing factors. When we go with unproven off-label use of multiple drugs, the statistics that apply to the normal population should get thrown out quickly.
As for individual rare events, I personally look at both death and disability-adjusted life years. A single episode of something like urosepsis is a huge impact even if it might be 0.5% or so incidence in the population. Possibly reversible impaired spermatogenesis if it even occurs is negligible to me in terms of DALYs. We can also think about it in terms of insurance - would you rather risk a category 5 hurricane at roughly a 1% chance per year or pay insurance for it? I would not. But people tend to become weirdly resistant to insuring for these sort of rare events that aren’t even that rare over a lifetime (30% chance). And that’s even if say insurance messed up the underwriting and gave favorable odds - a guaranteed investment.
Also, note that diseases that are “rare” are very much important to think about. These tail risks aren’t even 1%, but much higher when we run them cumulatively.
Most physicians are not familiar with a large number, if not the wide majority of rare diseases. I’ve seen a case of a lady that had Sjogren’s and it was missed by over 10 physicians (we have Epic Care Everywhere, so I’m sure based on the records - a relatively new feature that allowed me to deduce her condition) despite clinical symptoms being unambiguous. But to be fair, most physicians aren’t spending more than a bit of time digging the charts let alone all the possible medical records plus maybe 5-10 min in the patient’s room. Most physicians put all “rare diseases” on the low to zero priority list to read up on.
When you add all the “rare diseases” cumulatively, rare iatrogenic events, rare medication adverse events, and rare accidents (not motor vehicle accidents or other common accidents) - it can easily be 10%+ of patients that come in. And nearly all of them may not be getting optimal treatment that actually has a sizable impact on DALYs or death. I’ve literally caught a elderly woman with psychosis on a beta blocker as they were about to give her an antipsychotic which would have creeped onto the polypharmacy death and disability problem.
Meanwhile, we do not know if rapamycin plus canagliflozin and all the other things will actually extend DALYs relative to rapamycin in humans. Or even if rapamycin will extend it in the first place in humans. It’s a shot in the dark with our best guesses, currently monotherapy with rapamycin is considered suggestive evidence and not even up to a weak recommendation by consensus. If you look at various researchers in the field - about half or so are stating they are not taking rapamycin.