It is Challenging to Find Support for Evolutionary Trade-offs Between Reproduction and Aging in Human Data

The disposibility theory of aging is one of numerous evolutionary theories of aging that seek to explain why aging exists and is near universal across species. In this case, aging is viewed as the inevitable result of trade-offs between resources allocated to reproduction versus resources allocated to tissue maintenance. Like near all evolutionary theories, and particularly those relating to aging, the models and the science are much debated.

Since there is some variation between individuals within a species, one should expect to find a distribution of outcomes for any given trade-off when comparing large numbers of individuals of a given species. In this case, for this view of the origin of aging, we should expect to see that greater reproductive success correlates with a worse outcome in later life. Meaning a faster decline, more age-related disease, and a shorter life expectancy.

In today's open access paper, researchers compare parity (number of children carried to term) with later frailty in a human population. They indeed observe that more births tends to correlate with greater age-related frailty. The challenge with human data is that one can always come up with other plausible explanations for this effect, completely unrelated to fundamental biology. That the effect is similar in men and women somewhat sabotages any thoughts of a biological or physiological cost to childbirth as a dominant mechanism, for example.

Frailty: A cost incurred by reproduction?

The disposability theory of ageing proposes that investing in reproduction, at the cost of somatic maintenance, leads to senescence. In humans, the theory predicts that those with more children will have shorter lives. Researchers used a historical dataset from the British aristocracy to demonstrate that females with the longest life span had fewer children relative to the whole sample. Indeed, almost 50% of females who lived to 80 years and over were childless. A similar relationship between parity and longevity was found in males. The paper was criticized in the literature, particularly with regards to the quality of the data. Despite a sustained research effort and strong theoretical expectations, evidence to support a reproduction-longevity trade-off in humans is not strong. Studies of historical and contemporary cohorts have not found a consistent association between parity and longevity - no association, as well as positive and negative associations, have all been reported.

Most studies to date have tested evolutionary theories of senescence by focusing on the relationship between parity and survival (usually measured in terms of longevity). However, it is possible that survival is too crude a measure of senescence and, as a result, the 'real' cost incurred by reproduction has not been elucidated. Whilst studies have examined other health outcomes, such as physical, functional and cognitive impairment, self-rated health and limiting long-term illnesses in older males and females, findings have not been consistent. Examining the relationships between parity and individual domains of health may not be the best methodology to address the hypothesis because impairment profiles vary significantly in the older adult population and measures of individual domains do not capture all adults with poor health. 'Frailty', on the other hand, is a multidimensional measure of health status that may help to better define the long-term consequences (whether they be harms or benefits) of human reproduction.

The aims of this study were to examine the cross-sectional relationship between parity and later life frailty (represented by the Frailty Index) and to explore whether this relationship is influenced by sex. Data from the English Longitudinal Study of Ageing (ELSA) were used to test two key hypotheses: firstly, that higher parity is associated with greater frailty, indicating a 'parity-frailty trade-off' and secondly, that sex differences in frailty are greater at higher parities than at lower parities due to sex differences in the physiological costs of childbearing.

We found that the most parous adults were the most frail, providing weak evidence for a 'parity-frailty trade-off'. The relationship between parity and frailty was similar for both sexes, and thus the results suggest that behavioral and social factors associated with rearing many children may be more relevant to the parity-frailty relationship than the physiological burden of childbearing. Parity-frailty trade-off may manifest in older males and females with high parity due to economic strain, disruption of occupational attainment, and psychological stress. In addition, high parity may negatively influence lifestyle habits such as dietary choices and physical activity in both sexes. These behavioural factors increase the risk of obesity and its metabolic complications, which in turn, increase the risk of frailty.

An alternative theory is that selection effects confound the relationship between high parity and frailty. For example, lower levels of education level are associated with particular reproductive characteristics, such as early parenthood and higher overall parity, as well as later life frailty. However, in this study, education was not found to have a significant impact on the parity-frailty relationship.

Comments

Re Hey ! Just a 2 cents.

I would say it is because some studies do not see a real cost to it. They talk of cost, but not much quantifying or qualifying. And there Is a (evolution) trade-off, with that said, evolution 'found ways' to mitigate the costs (for example, Salmon Fish......salmon fish normally die in 3 years...but when parasited by a parasite, the parasite, is able to increase its host's (the salmon's) lifespan dramatically - to nearly 13 years; and it is sexual reproductive for nearly all that time; while normal unparasited salmon becomes sexually senescent quick and thus die early). Evolution saw that 'sexual competition' being sexual competitive has advantages; like specie survival - reproduction; the lemurs with the biggest testitcules - get lots of sex and lots of babies - solid specie survival. In humans, it's not so, longevity/late parenting is more important.

It just is that way, reproduction is not free (in most mammals vertebrates), it is costly resource wise; it is not an 'automated dispensing machine' because sperm is renewed and no effect on lifespan. Ablation of sexual organs, such as men becoming euneuchs, or women becoming unable to carry/birth child (ovary cut/destruction/uterus removal), causes effect in terms of healthspan; euneuchs were shown (as a sort of trend) to live longer lives; Not Necessarily, but yes, infertility and immaturation of the sexual organ/or complete removal; would now do the relocating of resources; because no more reproduction possibility; no more sexual resources Investment possible. That leaves More for the Self/recipient's overall body (somatic tissue repair/maintenance/DNA repair/synthesis). Which are causal to an individual's longevity. Same for women - centenarians women were childless (in general trend). My grand-mother (92 years old) is of the few women who lived nearly to become a centenarian and had children (2); but as the women reach closer and closer to the big 100; the less and less kids they had in their life. One study had shown that Young girls who become pubert quick and 'sexually capable' quick (much quicker than boys) had Quicker Menopause -Later (decades later), in their life; and thus, became frail quicker in their adult life (leading to a shorter lifespan and faster disease arrivals/health crippling/menopause).

The reason why it would not, necessarily, lead to longer lifespan to remove sexual resources costs (but only a 'rough trend' in animals) is because sexual reproduction/sexual maturation and sexual organ are related to 'growth' (in part), and IGF (insulin growth factor) is an important (growth) element/factor for health to avoid fragility/frailty (IGF is crucial for neuron survival; likewise for BDNF (Brain Derived Neutrophic Factor), it is likewise for HGH (human growth hormones) and other pituiary hormones that promote growth of the body - renewing tissues but At a Cost - mTOR; mTOR will be activated by IGF/HGH/EGF/VEGF and whatever other GFs; this means Replicative Senescence acceleration by mTOR geronconversion to replicative senescence. And, in later phases, that means arrival of p21, p53, p16 tumor suppressors with inflammation (TNF-a, IL-6, INF-g, etc...).

Sexual hormones (testosterone, oestrogen) are directly linked to growth but Also telomerase; such oestrogenic receptors in brain controlling telomerase Activity. Sure enough, when you remove ovaries or face menopause, there is a drop of oestrogen; or in men, there can be a drop of testosterone (euneuchs). These can lead to Less mTOR; thus farther replicative senescence - Except less health promotion (by fall of IGF, fall of growth/sexual hormones, and in some point, Less Telomerase too; which will mean faster replicative senescence by less telomere lengthening); with that said, there should be a reduction of telomere shortening rate - because you remove growth/sexual reproduction cost - so, in effect, you 'glide/coast' with whatever resources you have left, but they are now not divided anymore in the body (between somatic repairs Vs. sexual reproduction); they can fully be put on repair/longevity.

Menopause and Andropause are accompanied by less telomerase and that has strong effect on health; women can suffer very badly after these events such as heart Attack in women (because no more telomerase/oestrogen), while men become infertile and can fall into frailty - testosterone gone, no more muscle formation. Sarcopenia., myodeficiency. Sexual resources are at the 'crossroad' between 'growth', 'reproduction', 'health/frailty' and 'longevity'...it is seen in Dwarfs people; such as Ashke Nazi small stature people, Dwarfs pueblans and other smaller people that can live longer lifespans; and May have sexual retardation/sexless/slow sex organ maturation. Thus, may have neotenous features or in puberty much later/longer. It reaches the fact that Groenland sharks take 150 years before reaching their puberty 'to be sexual capable'...they live 400+ years...humans live longe livespans because they push back that period the latest possible (10-13 years old before sexual capable), while a mouse is highly reproductive in no time; and dies in no time too. All this points to costs of reproduction that are 'tallied' in the resources avail for an individual -and the lifespan that will come out of it; should there be more or less resources for that purpose/end.

CR does same thing; it, mostly, is a sexual infertilizer..it makes one more infertile and relocates sexual resources towards DNA maintenance (during a period of famine/fasting/calorie restriction). It becomes a clear 'survival of the individual' over the survival of the specie...otherwise it would boost sexual resources in a 'all out last ditch effort'; in other words, we would burn the candles by both ends; to be Highly sexually reproductive...and die rapidly;
like a mouce once again. But, reduction of calories, and espeically reduction of glucose....have an effect (on mTOR/replicative senescence) by CR. CR reduces mTOR, reduces metabolism and reduces hyperglycemia (glucose overload and improves WBGD (whole body glucose disposal) by using fat as fuel/ketose instead of relying too much on glucose/carbs);

My take is mTOR/IGF are totally important axis for seuxal reproduction and thus 'Limit' lifespan by the Replicative Senescence acquiry (by mTOR). Glucose -> Insulin (excess/Diabetes) -> Insulin Growth Factor IGF -> Sex Hormones -> Sexual Reproduction -> mTOR -> Faster Replicative Senescence -> Faster Telomere erosion -> Compensation by sex hormonal Telomerase but still (more) Net Loss than net gain (it is Overcompensation by telomerase) for accelerated telomer erosion -> Less DNA repair resources left by sex reproduction resources cost/consumption -> Accelerated Body/Sex Growth and Cell-Size Growth (GFs) -> Enlarged Cells -> Faster senesnce -> Shortened Lifespan.

Carbs are important for being sexually performant, because glucose needed for insulin/sexual/hormones endocrine signaling and thus, insulin growth factors/human growth factors/sexual growth factors.

Animal studies showed that sexual reproduction is not free. Human studies showed it too.
From women obtaining DNA lesions with so many pregnancies, too aviary studies showing that birds cells have a Telomere Shortening Rate Acceleration - Exactly - at the moment they have sex reproduction; and then it rate slows once again, once sex reproduction is finished.

Periods of intense growth, like puberty, show dramatic Telomere erosion rate/loss; like in the order of HGPS people/cells; but only for that period to become sexually 'mature/adult/capable'.
Then, the body slows the shortening rate once more (just like in birds after sexual reproduction).
In mice, it is 10-100x times faster shortening rate and Lots of sexual reproduction. Mice thus live 2 years.

Just a 2cents.

PS: The saying is: ''There is In Vivo, There is In Vitro, and There is In Utero''...like that old Kurt Cobain music album. Forgot, Ex vivo, Ex vitro and Ex utero. Just like your ex. (/s) Let's say that is a lot of O's.

Posted by: CANanonymity at July 11th, 2020 3:05 AM

@Reason Hello Reason! What is your opinion on patents? Are they helping to do research and innovate? Or the contrary? Thanks

Posted by: Josep at July 11th, 2020 4:58 AM

@Josep: Thats a Q I've thought about much but haven't come to an answer. The most interesting model to study is India which have the most "Open-Source" culture. I think we will see their system will be competitive and maybe surpass the western IP model in coming decades. Then it will be easier to compare those 2. The Indian model may be superior but no-one knows today. I think a combination in same way I think a combination between capitalism and socialism is the best model.

Posted by: Norse at July 11th, 2020 6:35 AM

The patents are a compromise that allows an inventor to profit from disclosure of an invention by having a time limited monopoly. There are several fair use and public good preemptive loopholes. Without patents the producers would be sticking to trade secrets and obscuring the production chains.

The system is far from perfect. From one side we have patent trolls, from the other for bigger players is easier to find a way around of a patent held by smaller party.

For an investor if an improvement is not patentable it's a higher risk.

Don't forget also that a patent takes many years to be put in production and than it expires after a couple of decades. For example Dasatinib us associated with a bunch of patents. Some have expired, and most will expire in a couple of years.

Posted by: Cuberat at July 11th, 2020 1:13 PM

@Cuberat. Ok thanks. By the way, do you know where I can buy follistatin legally, as we talked the other day? Thanks

Posted by: Josep at July 11th, 2020 6:22 PM

@Josep
I haven't bought F myself but a quick googling finds https://www.peptidesciences.com/follistatin-315-1mg

It is labeled as "research only" , probably to avoid any lawsuits . They might not be too keen to sell it to individuals .

But I would try with body builders. In some states it is illegal to sell steroids but buying for research purposes should be legal. I am not a lawyer and might be wrong. Each jurisdivtion has its own quirks. I think that even if it is considered illegal buying folistatin it might be not criminal or a felony but rather bring danger of fines. If you want to be sure you are on the right side of the law you have to consult a lawyer. Unfortunately, even they might not be 100% sure, unless specializing in the area. For example if you ask two different tax lawyers charging 1000/h you might get different opinions on what is considered legal tax optimisation...

Posted by: Cuberat at July 11th, 2020 8:26 PM

Update. In US the anabolic steroids are schedule III drugs which can lead to one year prison term for possession without prescription. Folistatin seems not to be on any schedule, though. However, if you impersonate a lab researcher or any official might be

Posted by: Cuberat at July 11th, 2020 8:48 PM

@cuberat. Ok thanks. I'm form Europe, so I guess here it's even more restricted. I think I will wait untill it is more mainstream

Posted by: Josep at July 12th, 2020 3:15 AM

I'm from Norway the most restrictive country in Europe. Here alpha lipoid acid amongst many others unharmfull compounds are illegal to import. Im thinking about having a 2nd passport and moving to Spain or other places because of that. Spain is good for biotech.

Posted by: thomas.a at July 12th, 2020 5:17 AM

@Cuberat the Peptide Sciences URL. At their blog theres an interesting article:

Epithalon Peptide Induces Telomerase Activity and Telomere Elongation in Human Somatic Cells and Overcomes the Hayflick Limit

https://www.peptidesciences.com/blog

Posted by: Gekki at July 12th, 2020 5:54 AM

@thomas.a
Can you forwarda link to the legal status (preferably in English). It is interesting to know the legal status of obscure compounds by country, especially if publishing self experiments under the real name.

@Josep
I was using steroids as a proxy of what to expect in any legal environment. Folistatin seems not to be on any schedule, but producers might not be willing to sell it to individuals. As for experimenting with it, I don't recommend it. It is very expensive, not that effective and probably has side effects. Compared to an unproven gene therapy it is several orders of magnitude cheaper and safer , of course.

Posted by: Cuberat at July 12th, 2020 7:46 AM

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