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What are some experimental methods we can use to study the aging process?

Image credit: https://pubchem.ncbi.nlm.nih.gov/compound/D-galactose#section=Biologic-Description

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Brett M.
Brett M. Dec 03, 2020

[1]https://brainstorming.com/search?search=anti-aging

[2]Liu H , Zhang X , Xiao J , Song M , Cao Y , Xiao H , Liu X . Astaxanthin attenuates d-galactose-induced brain aging in rats by ameliorating oxidative stress, mitochondrial dysfunction, and regulating metabolic markers. Food Funct. 2020 May 1;11(5):4103-4113. doi: 10.1039/d0fo00633e. Epub 2020 Apr 28. PMID: 32343758.

[3]Hou J, Yun Y, Xue J, Sun M, Kim S. D‑galactose induces astrocytic aging and contributes to astrocytoma progression and chemoresistance via cellular senescence. Mol Med Rep. 2019 Nov;20(5):4111-4118. doi: 10.3892/mmr.2019.10677. Epub 2019 Sep 12. PMID: 31545444; PMCID: PMC6797969.

[4]Budni J, Garcez ML, Mina F, Bellettini-Santos T, da Silva S, Luz APD, Schiavo GL, Batista-Silva H, Scaini G, Streck EL, Quevedo J. The oral administration of D-galactose induces abnormalities within the mitochondrial respiratory chain in the brain of rats. Metab Brain Dis. 2017 Jun;32(3):811-817. doi: 10.1007/s11011-017-9972-9. Epub 2017 Feb 24. PMID: 28236040.

[5]Shwe T, Bo-Htay C, Leech T, Ongnok B, Jaiwongkum T, Kerdphoo S, Palee S, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. D-galactose-induced aging does not cause further deterioration in brain pathologies and cognitive decline in the obese condition. Exp Gerontol. 2020 Sep;138:111001. doi: 10.1016/j.exger.2020.111001. Epub 2020 Jun 6. PMID: 32522583.

[6]Qu Z, Zhang J, Yang H, Huo L, Gao J, Chen H, Gao W. Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat. Physiol Behav. 2016 Feb 1;154:114-25. doi: 10.1016/j.physbeh.2015.11.016. Epub 2015 Nov 22. PMID: 26592138.

[7]Liu H , Zhang X , Xiao J , Song M , Cao Y , Xiao H , Liu X . Astaxanthin attenuates d-galactose-induced brain aging in rats by ameliorating oxidative stress, mitochondrial dysfunction, and regulating metabolic markers. Food Funct. 2020 May 1;11(5):4103-4113. doi: 10.1039/d0fo00633e. Epub 2020 Apr 28. PMID: 32343758.

[8]Kou X, Li J, Liu X, Chang J, Zhao Q, Jia S, Fan J, Chen N. Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics. J Appl Physiol (1985). 2017 Jun 1;122(6):1462-1469. doi: 10.1152/japplphysiol.00018.2017. Epub 2017 Mar 16. PMID: 28302704.

[9]Cardoso A, Magano S, Marrana F, Andrade JP. D-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats. Rejuvenation Res. 2015 Dec;18(6):497-507. doi: 10.1089/rej.2015.1684. Epub 2015 Aug 20. PMID: 25936362; PMCID: PMC4685507.

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Creative contributions

Computational models to study ageing

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Subash Chapagain
Subash Chapagain Dec 04, 2020

[1]Kitano, H., 2002. Computational systems biology. Nature 420 (6912), 206–210

[2]Mark Mc Auley, Kathleen Mooney, Chapter 7 - Using Computational Models to Study Aging, Editor(s): Jeffrey L. Ram, P. Michael Conn, Conn's Handbook of Models for Human Aging (Second Edition), Academic Press, 2018

[3]Le Novère N, Hucka M, Mi H, Moodie S, Schreiber F, Sorokin A, Demir E, Wegner K, Aladjem MI, Wimalaratne SM, Bergman FT, Gauges R, Ghazal P, Kawaji H, Li L, Matsuoka Y, Villéger A, Boyd SE, Calzone L, Courtot M, Dogrusoz U, Freeman TC, Funahashi A, Ghosh S, Jouraku A, Kim S, Kolpakov F, Luna A, Sahle S, Schmidt E, Watterson S, Wu G, Goryanin I, Kell DB, Sander C, Sauro H, Snoep JL, Kohn K, Kitano H. The Systems Biology Graphical Notation. Nat Biotechnol. 2009 Aug;27(8):735-41. doi: 10.1038/nbt.1558. Epub 2009 Aug 7. Erratum in: Nat Biotechnol. 2009 Sep;27(9):864. PMID: 19668183.

[4]Qi, Q., Wattis, J.A., Byrne, H.M., 2014. Stochastic simulations of normal aging and Werner’s syndrome. Bull Math Biol 76 (6), 1241–1269.

[5]Hirt, B.V., Wattis, J.A., Preston, S.P., 2014. Modelling the regulation of telomere length: the effects of telomerase and G-quadruplex stabilising drugs. J Math Biol 68 (6), 1521–1552.

[6]Trusina, A., 2014. Stress induced telomere shortening: longer life with less mutations? BMC Syst Biol 8, 27.

[7]Kriete, A., Bosl, W.J., Booker, G., 2010. Rule-based cell systems model of aging using feedback loop motifs mediated by stress responses. PLoS Comput Biol 6 (6), e1000820.

[8]Brännmark, C., Nyman, E., Fagerholm, S., Bergenholm, L., Ekstrand, E.M., Cedersund, G., et al., 2013. Insulin signaling in type 2 diabetes: experimental and modeling analyses reveal mechanisms of insulin resistance in human adipocytes. J Biol Chem 288 (14), 9867–9880.

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Brett M.
Brett M.3 months ago
Thanks for your contribution! I have found computational modeling to be such an interesting tool, though I have never been able to take the time to quite understand it, so thank you for providing a brief overview--very informative.

As I am most interested in the concept of predictability, "Also, the model can be used to predict the temporal development of the system and it also offers flexibility update and cohesive input whereby different biological pathways can be taken into account," sounds like a very interesting utility of computational modeling.

Have these models only been used as predictive measures, or have they been correlated with actual outcomes? This is super interesting and I would love to know if there is evidence describing the accuracy in the model predictions (also, it may be too early as I am not sure how old this technology is).

As I'm thinking about the utility of this technology, I think this would be super useful to identify lifestyle patterns that individuals could take to promote longevity. Almost like a "cookbook" of longevity lifestyles in a sense, that you can pick from (or move between) to optimize your aging process. Very interesting contribution--thank you!
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Subash Chapagain
Subash Chapagain3 months ago
Thanks for the comment. Some of these models (for instance the one that looked into Cholesterol dynamics and the one IGF-like insulin signaling) have been reported to reflect the real outcomes. However, I think there is still a need for rigorous validation. Talking about the utility, like you said, in future if we could develop models not just for the biochemical reactions but also for the holistic effect of lifestyle choices, it would indeed be a leap for anti-ageing research. As more models become validated, we can expect that to happen: how much of physical activity of what sort, in synergy with what particular kind of diet and lifestyle choices could one follow so as to age the most slowly? This could be interesting if we could be advised by an AI assisted computer model.

Monitor the lifestyle of centenarians and compare it with that of others

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Shubhankar Kulkarni
Shubhankar Kulkarni Jan 08, 2021

[1]Willcox DC, Willcox BJ, Poon LW. Centenarian studies: important contributors to our understanding of the aging process and longevity. Curr Gerontol Geriatr Res. 2010;2010:484529. doi:10.1155/2010/484529

[2]Appel LJ. Dietary patterns and longevity: expanding the blue zones. Circulation. 2008 Jul 15;118(3):214-5. doi: 10.1161/CIRCULATIONAHA.108.788497. PMID: 18625902.

[3]Buettner D, Skemp S. Blue Zones: Lessons From the World's Longest Lived. Am J Lifestyle Med. 2016;10(5):318-321. Published 2016 Jul 7. doi:10.1177/1559827616637066

[4]Functionally significant insulin-like growth factor I receptor mutations in centenarians Yousin Suh, Gil Atzmon, Mi-Ook Cho, David Hwang, Bingrong Liu, Daniel J. Leahy, Nir Barzilai, Pinchas Cohen Proceedings of the National Academy of Sciences Mar 2008, 105 (9) 3438-3442; DOI: 10.1073/pnas.0705467105

[5]Bradley J. Willcox, D. Craig Willcox, Qimei He, J. David Curb, Makoto Suzuki, Siblings of Okinawan Centenarians Share Lifelong Mortality Advantages, The Journals of Gerontology: Series A, Volume 61, Issue 4, April 2006, Pages 345–354, https://doi.org/10.1093/gerona/61.4.345

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Brett M.
Brett M.2 months ago
Thanks for your contribution! You've highlighted a good point in measuring the aging process - while the diet is inherently important, it is not the sole mediator. Psychological and other physical factors (perhaps a combination) that you have highlighted are important to consider as well. In fact, group-based exercises in the aged Japenese population greatly benefit health status (https://pubmed.ncbi.nlm.nih.gov/28830443/) - a process that may be facilitated by having senior leaders in political and public health roles to promote exercise in the elderly (https://pubmed.ncbi.nlm.nih.gov/33008403/). This type of exercise clearly has social, psychological, and physical effects, and may all be working together to improve health status in old age.

Interestingly, serum albumin levels were found to protect against the decline in daily activities in the aged Chinese population (https://pubmed.ncbi.nlm.nih.gov/32605543/). As well, heart-rate variability appears to be linked to longevity (https://pubmed.ncbi.nlm.nih.gov/33041862/). These represent additional measures that could be assessed to understand the link between physiology and longevity.

Of course, adding this measurement with the other measures you have mentioned would be incredibly important, as this adds to the holistic approach you've described, which would definitely paint a better picture than assessing each component in isolation. Thanks again!
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Shubhankar Kulkarni
Shubhankar Kulkarni2 months ago
Brett M. Thank you for directing me towards the other studies. I did not know that albumin contributed significantly to the daily activity levels and, as an effect, to the energy levels of an individual and, ultimately, their lifespan.

I always knew that heart-rate variability decreases with age but I was hoping to find a difference between that of centenarians and octogenarians. But I think there are a few factors from the study that may have contributed to it. Firstly, the small sample size (20 is the maximum group size in the study). Secondly, the age difference between the young and the aged is too high, which shows an obvious difference in the heart-rate variability. Comparatively, the age difference between octogenarians and centenarians is less. The non-significant difference may be due to this reason. Thirdly, all the participants come from the same area and lifespan may not be a significant variable there. Who is to say that most of the octogenarian participants did not survive into their hundreds? Although not perfect, a way around this is to compare the siblings (or progeny) of the non-centenarians to the centenarians. Here is another study that compared the heart-rate variability of the aged population (above 75 years of age) and the centenarians and found significant differences (https://pubmed.ncbi.nlm.nih.gov/10545308/#:~:text=Heart%20rate%20variability%20(HRV)%20has,aged%20subjects%20and%20healthy%20centenarians.)

What we both are hinting at here is the exposome of an individual, which is "the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. An individual's exposure begins before birth and includes insults from environmental and occupational sources." (https://www.cdc.gov/niosh/topics/exposome/default.html#:~:text=The%20exposome%20can%20be%20defined,from%20environmental%20and%20occupational%20sources.) I hadn't come across this word earlier so thanks for sharing that, too!

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