Associations of Body Mass Index and Waist Circumference with 3-Year All-Cause Mortality Among the Oldest Old
Posted 04 June 2018 - 07:08 AM
Posted 04 June 2018 - 01:38 PM
You have to be careful when dealing with the very old on account of survivor bias. The same goes for higher blood pressure and higher cholesterol in the very old. I read an article not long ago - which I can't locate at the moment - that there's also speculation that those who manage to reach old age despite high cholesterol might have a genetic predisposition to deal very well with high cholesterol, and therefore have a more resilient physiology. So there might also be some kind of genetic predisposition in a subpopulation. Hard to generalize. It really does come down to individual differences. Which is why I don't necessarily see such results as "damning of CR" - it may simply be the case that various findings only apply to specific subpopulations. Remember, that at one point in one of the monkey studies the oldest surviving was a control on ad lib diet, a diabetic female - nobody would recommend DMT2 as a way of reaching old age.
Posted 04 June 2018 - 07:37 PM
I agree with Tom's comments, I don't think advising the elderly to become obese for longevity passes the sniff test. That said, eventually many (most?) old people develop some condition for take a fall, which lands them in a hospital or bed for weeks - and during those times, they may not be willing or able to eat, I suspect having considerable extra body fat would offer a distinct survival advantage for these events. I've read that many elderly in these situations instinctively just stop eating (and I've seen this first hand recently). We also know that fasting can be very good for the immune system, and is also recommended before chemotherapy, and can help in many different ways:
So for the very old, being able to fast for extended periods is likely an extremely valuable survival skill, and doing that on a serious CR physique seems questionable to me. But do you need to be obese? I don't think so. Having some fasting practice may be a good idea in one's elder years, plus these practice periods will double as a means to boost one's immune system:
Posted 04 June 2018 - 09:22 PM
TomBAvoider: ...there's also speculation that those who manage to reach old age despite high cholesterol might have a genetic predisposition to deal very well with high cholesterol, and therefore have a more resilient physiology.
Certain forms of cholesterol may have anti-cancer effects, creating a trade-off with increased cardiovascular disease risks. Lipoprotein (a) is an interesting case.
Puzzling role of genetic risk factors in human longevity: “risk alleles” as pro-longevity variants
Another established risk factor for CVD, lipoprotein (a) [Lp(a)], also shows a trade-off-like influence on major human diseases. Its elevated plasma levels are considered to be an independent risk factor for premature CHD, stroke and peripheral artery disease (Dahlen 1994; Enkhmaa et al. 2011; Erqou et al. 2009). Several LPA [lipoprotein, Lp(a)] genotypes, which result in elevated Lp(a) levels, were shown to increase the risk of CVD (Clarke et al. 2009). However, some of these genotypes were also found to be protective against cancer and other non-CVD disorders (Hsieh Wu 2011; Sawabe et al. 2012).
This indicates that the impact of the “risk genotypes” for CVD on all-cause mortality and longevity may not necessarily be detrimental. This possibility is supported by research on associations of Lp(a) blood levels with longevity and various health disorders. An earlier study reported that mean Lp(a) levels are about the same in centenarians and younger controls; moreover, a quarter of healthy centenarians had the Lp(a) levels that might put them at risk for atherosclerosis (Baggio et al. 1998). The authors concluded that either Lp(a) level is not a risk factor for CVD in the very old, or it is offset by unknown protective factors.
In a more recent longitudinal study of the Italian elderly (65–84 years of age), no significant association of Lp(a) serum levels with all-cause mortality was found (Solfrizzi et al. 2009). A meta-analysis of 36 prospective studies, with 126,634 participants in total, revealed that the high Lp(a) concentrations could indeed be considered a risk factor for CVD but not for non-vascular deaths including cancer deaths (Erqou et al. 2009). The trade-off-like influence of the Lp(a) on CVD and non-CVD related disorders might in part explain the lack of association of the Lp(a) levels with all-cause mortality.
That kind of longevity "trade-off" is by no means unusual:
Complex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. Here we argue that trade-off-like and conditional effects of genes can play central role in this phenomenon and in determining longevity.
Such effects may occur as result of: (i) antagonistic influence of gene on the development of different health disorders; (ii) change in the effect of gene on vulnerability to death with age (especially, from “bad” to “good”); (iii) gene–gene interaction; and (iv) gene–environment interaction, among other factors. A review of current knowledge provides many examples of genetic factors that may increase the risk of one disease but reduce chances of developing another serious health condition, or improve survival from it.
Factors that may increase risk of a major disease but attenuate manifestation of physical senescence are also discussed. Overall, available evidence suggests that the influence of a genetic variant on longevity may be negative, neutral or positive, depending on a delicate balance of the detrimental and beneficial effects of such variant on multiple health and aging related traits. This balance may change with age, internal and external environments, and depend on genetic surrounding. We conclude that trade-off-like and conditional genetic effects are very common and may result in situations when a disease “risk allele” can also be a pro-longevity variant, depending on context. We emphasize importance of considering such effects in both aging research and disease prevention.
Edited by Sibiriak, 04 June 2018 - 09:30 PM.
Posted 05 June 2018 - 07:18 AM
Another potential confounder might be if there is a correlation between wealth and body weight in this elderly Chinese cohort. It's well established here in the US that the wealthy live longer than the poor probably due to factors such as higher quality foods, better housing in more desirable environments, better healthcare, maybe less chronic stress, etc.
Edited by Todd Allen, 05 June 2018 - 07:20 AM.
Posted 05 June 2018 - 12:42 PM
Thank you, Sibirak for that paper. It's a super important one, with a great deal of bearing on everything that we discuss and any number of controversies we've been tackling. It's something that I've been increasingly aware of in recent years - it really comes down to individualized medicine, and there is not much that's "one size fits all". An intervention in one person might be beneficial or detrimental depending on a complex interplay between their genes and environment and stage of life. This I feel is also behind the many conflicting results in studies, which aren't usually designed to carefully select for all these factors. And all of them interact in very complex ways.
In fact, I like this paper so much, I'd like to re-post it in another section and give it its own thread! I'll post it in the General section of the board.