RNAi epigenetic demethylation drug drug causes c elegans to live twice as long as unmodified c elegans going from 30 day lifespan to 60 day lifespan; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889222/figure/F1/

[Treon Verdery]

The longest lived c elegans compared to undrugged c elegans is called vector + CCO1 daf2e1370, daf2e1370 did better at median but they both doubled longevity; isp1 (qm150) had greater surviving near median, but was like 58%



CCO1 RNAi was a single treatment rahter than a combined treatment

“Across eukaryotic species, mild mitochondrial stress can have beneficial effects on the lifespan of organisms. Mitochondrial dysfunction activates an unfolded protein response (UPR(mt)), a stress signaling mechanism designed to ensure mitochondrial homeostasis. Perturbation of mitochondria during larval development in C. elegans not only delays aging but also maintains UPR(mt) signaling, suggesting an epigenetic mechanism that modulates both longevity and mitochondrial proteostasis throughout life. We identify the conserved histone lysine demethylases jmjd-1.2/PHF8 and jmjd-3.1/JMJD3 as positive regulators of lifespan in response to mitochondrial dysfunction across species. Reduction of function of the demethylases potently suppresses longevity and UPR(mt) induction, while gain of function is sufficient to extend lifespan in a UPR(mt)-dependent manner. A systems genetics approach in the BXD mouse reference population further indicates conserved roles of the mammalian orthologs in longevity and UPR(mt) signaling. These findings illustrate an evolutionary conserved epigenetic mechanism that determines the rate of aging downstream of mitochondrial perturbations.”



So like they did this thing to mitochondria, and the epigenetics had more demthylase going on, so there were some histone DNA areas that got more demethylated, They demethylased the c elegans when they were larvae, suggesting a possible human prenatal longevity chemical (epigenetic), or noting epigenetics, something the mother can do for her children, or possibly something a grandmother can do for her grandchildren, mitochondrial stress causes c elegans to live twice as long and mice have the same genes, notably I read that nucleotide riboside (NR) or a lipid rich diet change the mitochondria from many and diminuative (NR) to plump and few (lipids), and that at the many and diminuative version the energy producing ability of the organism, and this has been verified with humans taking Nicotinic acid combined with ribose, could have similarities to the “mitochondrial stress” that makes the c elegans live twice as long, that suggests primate research, like on marmosets could find out if something like a NR enriched, or possibly just nicotinamide with ribose enriched, or just nicotinamide enriched diet or possibly just ribose enriched beneficial at mice and marmosets diet during pregnancy is beneficial, along with the studies of people with naturally demethylated mitochondrial uncoupling areas at their histones found at databases guiding enhanced preoptimization human genetics and epigenetics



Notably it is possible to grow human oocytes from a cheek swab, so a woman can do a cheek swab, grow some oocytes (eggs), have their epignetics modified, notably as well as among others, with particular demethylases, then her direct progeny get the longevity benefit; this immediate progeny longevity epigenetics benefit could be verified with mice as well as finding out that actual amount of lifespan increase at a mammal; notably it is possible that the demethylases that cause mitochondrial protein uncoupling UCPmt epigenetics that double the longevity of the c elegans may also have completely different beneficial effects, if these demthylators have other beneficial effects then along with the longevity benefit they might have cell culture oocyte babies to say, prevent heart disease, or halve cancer risk when there is a previous generational occurence, so this longevity epigenetic modification to human oocytes has both a “conservatively get rid of illness” attraction component as well as a “my children will live a really time” component, which combined or separately reaches more people



Note though they have to figure out the benefit of demethylation that effects (uncouples) mitochondrial function possibly looking at medical records of individuals epigenetics at health maintenance organzations records or other databases to find hundreds or thousands of people, out of hundreds of thousands or millions of people, that have these histone demethylase epigenetics naturally; then measures like g (like iq), big five personality type, subjective well being, quantifications of beneficial or aversive life events, n external, if possible video based quantification of social fluency nd attractiveness, noting mitochondrial energy regulation during preganancy could effect birth weight, facial feature development, and body proportions; If all of these are at first standard deviation (about the same as 2/3 of other people), or have a higher concentration of characteristics to the right of one standard deviation, that is better than 2/3 of people, then demethylation of areas of oocyte (egg) histones is a highly beneficial thing people could actively seek. Also fiding out the epigenetic variants amongst those that naturally have demethylated epigenetics of mitochondrial uncoupling, the notable benefit being longevity, could find versions among humans that are actually better than the published data on mice and nonmammals, like there could be an genetic or epigenetic subgroup that has 40% more lifespan extension at their parents and grandparents ages than the other demethylase epigenetic humans, who also are quantified living longer than the 2019 population median; also subgroups of the long lived demethylation histone group that have higher g (like iq),



It is also possible that when screening databases to find people with naturally occuring demethylase of mitochondrial uncoupling persons high ceoncentrations at some regions, lifestyles, or direct genetics may be found, that could be because because it is possible genetics can also drive epigenetics, and then groups of those people could be looked at to find out if they have some endogenous production of an epigenetic modifier that demethylates the genetics of their oocytes as well as of the rest of their body,



Making sure this is beneficial to humans is suggested at, “One of the most dramatic examples in which early events have effects on longevity is found in the nematode C. elegans, in which mitochondrial stress during development can cause nearly a doubling of the animal's lifespan (Dillin et al., 2002a). The timing and degree of mitochondrial dysfunction is highly selective: it must occur during a specific L3/L4 larval transition in order to cause lifespan extension, a time during which a heavy amount of germline-specific mitochondrial biogenesis also occurs (Rea et al., 2007; Tsang and Lemire, 2002). In contrast, mitochondrial dysfunction that is too severe or which is implemented too early or late can have a negative effect on lifespan. In many cases, titrating a level of dysfunction is absolutely required in order to observe an extension of lifespan (Rea et al., 2007). Longevity caused by mitochondrial dysfunction also often fails to generate universal health benefits, as organisms may live longer but exhibit developmental delay and a drastic reduction in reproductive fitness (Dillin et al., 2002a; Lee et al., 2003). These effects are surprisingly conserved: in yeast, flies, and mice, mitochondrial dysfunction can delay the aging process (Copeland et al., 2009; Dell'agnello et al., 2007; Dillin et al., 2002a; Feng et al., 2001; Kirchman et al., 1999; Lee et al., 2003; Liu et al., 2005), but, when occurring later in life, has deleterious effects and is associated with age-onset neurodegenerative diseases, directly contributing to their pathologies (Schon and Przedborski, 2011).