Castration Delays Epigenetic Aging in Male Sheep
Castration is known to extend life in male sheep. Researchers here show that epigenetic clocks constructed for this species show the expected slowing of epigenetic aging following castration. This is a way to dig deeper into the question of how it is that females live longer than males in mammalian species, an exploration of which mechanisms are important in determining that outcome. It is also a way to further explore how epigenetic clocks relate to biological aging. Since the clocks are constructed by machine learning approaches applied to epigenetic data, it remains far from clear as to what exactly they measure under the hood, meaning which of the processes of aging are driving changes in specific epigenetic marks used in the clocks.
In mammals, females generally live longer than males. Nevertheless, the mechanisms underpinning sex-dependent longevity are currently unclear. Epigenetic clocks are powerful biological biomarkers capable of precisely estimating chronological age and identifying novel factors influencing the aging rate using only DNA methylation data. In this study, we developed the first epigenetic clock for domesticated sheep (Ovis aries), which can predict chronological age with a median absolute error of 5.1 months. We have discovered that castrated male sheep have a decelerated aging rate compared to intact males, mediated at least in part by the removal of androgens.
Furthermore, we identified several androgen-sensitive CpG dinucleotides that become progressively hypomethylated with age in intact males, but remain stable in castrated males and females. Comparable sex-specific methylation differences in MKLN1 also exist in bat skin and a range of mouse tissues that have high androgen receptor expression, indicating that it may drive androgen-dependent hypomethylation in divergent mammalian species. In characterizing these sites, we identify biologically plausible mechanisms explaining how androgens drive male-accelerated aging.
Unrelated, but does anyone know about Hevolution, mentioned here by Nir Barzilai, the mystery non-profit who is going to fund TAME?
https://www.lifespan.io/news/dr-nir-barzilai-we-can-live-healthier-for-longer/
Hey there! Just a 2 cents.
This is the euneuch homology in humans, castrated monks/men that lived longer lifespan due to lifelong sexual abstinence/amorphism (by not having any more testis/not producing sperm); being sexually amorph is a double-edged sword; they say ''because androgens removal''; yes, testosterone...
Thus, it is the sexual reproduction vs longevity resources explanation; they relocate the resources from sexual resources to DNA somatic/repair tissue maintenance (for longevity).
Longevity Vs Sexual Reproduction
It's once more the 'resources' thing, where they go, because we don't ahve infinite amount of them; thus, it is different strategy. I.e. resources towards sexual organs/capability, mean sexual reproduction 'sexual fitness'; while resources towards tissue maintenance, means 'longevity/health fitness'..
Mouse live short-lives because they are HyperSexual...while, other rodents taht are Far More sexually Amorph/Impotent/Unfertile...living much long lives. It's not so much the sexual resources, it's that they put a whole lot more towards longevity (rather than reproduction and reproduction & Puberty...are Delayed...a lot; naked mole rat that live 10 times longer than mouse are 'late bloomers' - very late puberty...like humans they all live long lives; bowhead whales and greenland shark....live centuries...they become 'sexually capable/pubert'..at like 100+ years...that tells you that sexual capabiliy is pushed back the latest possible; hence, they live ultra-long lives).
Because sexual reproduction has a cost (a bio/bodily resource cost - this 'removed/substracted' from your longevity capability; cause it's all about 'how much' resourcse you got).
Though We live 100+ years...and we can Still Reproduce....euneuch or not...castrated or not...
When castration happens it just is a 'boost' if you will...like CR/Calorie Restriction, same thing...it diverts resources; in CR, resources are 'kept/conserved' towards maintenance..because there is reduction in calorie/famine/drought/fasting....thus, you Have to conserve resources to survive.
This is a evolutive Strategy...(to survive famine/drought)...
CR has been shown to Reduce Sexual Capapility..it's a side-effect of CR; you become less reproductive/fertile...because there is Less Calories coming in...that has been proven.
CR Blocks mTOR/IGF...Calories -> mTOR/IGF; mTOR -> geroconversion to senescence...IGF is needed for body growth (insulin Growth factor; HGH, IGF..and others.. Sexual Growth Factors); you need Minimum of It...because mTOR...overactivation -> senescence. (IGF/mTOR are Needed to protect neurons...neuron die when insuling/IGF is Too Low...because you Need a minium level of IGF; it'S why dwarfism and euneuch may have other body problems; No Growth?...can be bad too; no sexual growth...well no reproduciton).
CR made testis and ovaries - 'struggle'....if you will..in the sense that the testis could Shrink during CR or output less in sertoli/leydig cells...it goes to show that when you 'strapped with (less) resources'...the body has to Compromise somewhere (a balance/offset : longevity vs reproduction (resources 'tug-of-war')...it will reduce your sexual 'output'. Thus, your 'brood-size'(the number of children) you can make - While on CR - is Less...again that has been proven in mouse...animals, etc... because Less Resources...by LEss Food/Calories - thus, less energy (Kj - Kiljoules (from calories)).
CR Takes Away the Sexual Resources..to survive....during a stressful situation (famine/food drought).
Animals that are castrated (humans, like euneuchs...that live longer lifespan)...are diverting their resources (just like CR does), and thus they live longer healthier lifespans...but they do this at the cost of loss of reproduction capability...
With that said, there is still the conundrum/paradox....why then are some centenarians..that lived long lifespans (100 years+...) and HAD children ALSO....so they made lots of sex....EVEN SO.
This paradox...is explained by the sexual senescence 'of 'aging'....which is Menopause and Andropause....where the hormones (estrogen/testosterone) drop and then you can die of a disease caused by sexual senescence phases later (around 50-55 years old)...
The salmon dies in 3 yaers....it becomes sexually senescent very quickly....while the parasited salmon lives 13 years - almost 5 TIMES...longer..and is Not sexually senescent..very much sexually active for 13 yaerse.....thus, it means that sexually capability has benefits not just costs...and that is due to endocrinal/hormonal activation of 'repair/longevity - Too'...for example, estrogen was found to regulate brain hTERT receptors; thus, telomerase; telomerase has been shown to increase lifespan; when you are sexually capable you increase telomerase (via estrogen, while in men testosterone, via aromatase), Telomerase protects DNA...slow telomere slow...
What about studies that said sexually reproduction Accelerate Telomere Loss/erosion..that's because sexually reproduction is costly Itself...but the body tries to compensate (with hormones activating TERT for example; it's a compensatory mechanism); bird studies showed that when they become pubert and make babies...there is telomere erosion acceleration...
While in humans, it was demonstrated that women whom were high gravidity (large broad...many kids), have more mitochondrial DNA lesions...per extra kid made....thus, it'S expensive to 'have sex/make spermatozoid/ovules...it'S not free'....and the 'act' (sexual) is also 'testing' on the body...all this will shown in telomers/DNA...and is why you can see people die younger of excess sexual reproduction..it's costly. - to them. against their Own Life. Because your life is Resources Limited.
Centenarians - that beat euneuchs who castrated - are the paradox...they had children...but we see a pattern. centenaraisn IN General Had NO children...or almost none...1 child or like '1.5' child...that's it- MOST - centenarian women...Did Not..have a family of 25 kids....
And that's explanatory...it means - Resources Kept For Self....and Surely,, it helped them reach 100 yaers...the Cost for that..its Not having a family of 24 kids....
While a woman High Gravidity...with 50some kids...she cuts herself her life...because it was costly all thse children - on herself/on her Own resources (for her Own Longevity).
Longevity VS reproduction
Women taht have 24 kids..it is a very Self-Less Act...because they are Basically GIVING THEMSELVES entirely...for their children...cutting so much of their Own (body/longevity) resources..to be able to have such a large family..is a very selfless act...very noble and altruist (these women are the Continuators of Humanity); for without them, no more kids....no more humanity....it is At the Cost of Their Own Life.
Now women/men have very few kids..they are basically 'castrated'...like the eunuchs...but Not entirelly...that is the centenarian...they can be amorph..but you Don't Want that..why?
Because menopause/andropause..you Always want to Maintain sexually capability but Use Less of It...in essence..you do less of it..but When You Do It..You Are Capable..of doing it...you are Not Amorph/Infertile/impotent.
Because, that IS the entry into menopause/andropause tec...
Centenarians where Not amorph...they were just 'lesser active'...simple as that.
There is 'sexually dead'...and 'sexually sparingly' (and 'hypersexual or sexually active)...choose the latter (sparringly - but very much capable -whenever called; it's like a well-oiled machine...you use it Less...does not mean it is rusted..it just is 'conservative/sleeping' until next use...the latest possible). It's the old saying 'conserve yourself (but don't stop anything Totally neither)' (and you will live longer). Or 'la modération a bien meilleur goût' ('moderation has a much better taste').
'Take some, leave some', like, a balanced-life.
Just a 2 cents.
" -- Call it making the best of a potentially bad situation. Eunuchs -- castrated men -- live nearly 20 years longer than other men, a new study has found.
The study of over 80 eunuchs from the Chosun Dynasty, which ruled in Korea from 1392 to 1897, looked at the world's only known record of eunuchs' lives and compared them to genealogical records of other men of similar social rank. The researchers cross-checked their results with other royal records."
https://abcnews.go.com/Health/castration-men-live-longer-eunuchs-studied-korean-records/story?id=17310420
I don't know that data from 1392 to 1897 is all that reliable though.
And then there is this to possibly consider
"All castrated males have an increased risk of developing sarcopenia, and becoming overweight. Wilson and Roehrborn note that eunuchs have historically suffered from skeletal problems such as osteoporosis and kyphosis; this is especially true of elderly eunuchs, and eunuchs castrated at earlier ages."
https://www.lesswrong.com/posts/2w9FEdFiMwnGLbAZf/effects-of-castration-on-the-life-expectancy-of-contemporary
Hi Brad! Thanks for that. Just a 2 cents.
Exactly... it is not a 'sure fire thing'... castration can have severe health effects (as you mentioned); and relates to IGF (insulin growth factor) and sexual GFs; it is cut down and then you create a sort of 'sexual sarcopenia'; IGF is important to protect against muscle loss and neuron loss - it increases health - at the cost of mTOR activation (senescence/cell cycle population doubling shortening); in other words, it is a 'negative compensatory' mechanism..it's meant to safeguard your health/fitness/vigor (even sexual vigor/potency), but the Cost for that, is that there is activation of the mTOR (mechanistic target of rapamycin compleX); which responsable for accelerating replicative senescence of cells;...
thus it means a 'negative 'boost''...evolution found a way: ''I'll keep you healthy/vigorous/sexually capable (to make reproduction and make specie survival (the whole evolution strategy))...etc...but there is a But. You will die faster because that is Costly - whenever you overdo it - senescence''.
This is why sexual reproduction must always be a Sparringly thing, never in excess or never be abolished neither (because then, you enter menopause/andropause -> acceleration of death);
humans that lived Longer - Pushed Back - the menppose/andropause...women/men that become menauposed/andropaused - later...like when they hit 60-70...is Better...and it was demonstrated they are sexually reproduction a Much Longer Time (just like that Parasited Salmon living 13 years and being sexually capapble Longer by stopping Sexual Senescence).
Eunuchs are basically removing the Costs of sexual reproduction (thus could live an extra 10-20 years) - but - At the Cost of Fitness Loss (by loss of IGF/Growth Hormones/Sexual Hormones)....this can mean arrival of 'health/frailty diseases' - sarcopenia, osteoporosis, balding...etc
Bottom-line, don'T be castrated, keep your (family) jewels, and push back that later menopause/andropause as best as you can; sex life should be a 'normal' part of a Healthy Life..so long as it is not abused of (cause...costs to your lifespan/longevity)...thus,
Sparringly.
Just a 2 cents.
Meanwhile... some researchers work on things relevant for humans...
An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging
https://www.nature.com/articles/s43587-021-00082-y
While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8-96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The strongest contributor to iAge was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling and poor vascular function. Furthermore, aging endothelial cells in human and mice show loss of function, cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. In conclusion, we identify a key role of CXCL9 in age-related chronic inflammation and derive a metric for multimorbidity that can be utilized for the early detection of age-related clinical phenotypes.