Aging and longevity - Revision history

Geroscientist: /* What is aging? */

2024-07-21T12:35:18Z

What is aging?

← Older revision		Revision as of 12:35, 21 July 2024
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	[[File:Updated deaths and aging.png\|alt=\|thumb\|618x618px\|Incidence of all age-related diseases increases exponentially with increasing age]]		[[File:Updated deaths and aging.png\|alt=\|thumb\|618x618px\|Incidence of all age-related diseases increases exponentially with increasing age]]
	People have yearned for the fountain of youth all throughout history. However, until recently, there has not been a concerted research effort to address ~~the~~ aging of ~~cells, tissues and and organs~~. In the modern era, humanity supports research towards the cure of age-related diseases (e.g. Alzheimer’s, heart disease, and [[Aging and Cancer\|most cancers]]) – a desire present at every level of human organization that spans across individuals, communities, and society. This reflects a core human desire to be healthy. Yet, recognizing that humanity should strive towards a cure for aging is a sentiment that does not attract such widespread popularity.		People have yearned for the fountain of youth all throughout history. However, until recently, there has not been a concerted research effort to address biological aging as a cause of disease. In the modern era, humanity supports research towards the cure of age-related diseases (e.g. Alzheimer’s, heart disease, and [[Aging and Cancer\|most cancers]]) – a desire present at every level of human organization that spans across individuals, communities, and society. This reflects a core human desire to be healthy. Yet, recognizing that humanity should strive towards a cure for biological aging is a sentiment that does not attract such widespread popularity.

	Lack of societal support stems from two fundamental misconceptions – that ‘aging’ merely represents the natural chronological passage of time, and that aging is an entirely separate category from ''age-related disease.''<ref>Sierra, F. (2016). The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. ''Cold Spring Harbor perspectives in medicine'', ''6''(4), a025163.</ref> In contrast, the biology of aging research field (biogerontology) ~~understands~~ the mechanisms of aging as the root cause of most of society’s most prevalent, costly, and debilitating diseases.<ref name=":2">[https://www.nature.com/articles/s41586-019-1365-2 Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. ''Nature'', ''571''(7764), 183-192.]</ref><ref name=":14">[[Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. Nature Reviews Drug Discovery, 19(8), 513-532.\|Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]]</ref><ref name=":3">[[Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. Aging cell, 14(4), 497-510.\|Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. ''Aging cell'', ''14''(4), 497-510.]]</ref>		Lack of societal support stems from two fundamental misconceptions – that ‘aging’ merely represents the natural chronological passage of time, and that aging is an entirely separate category from ''age-related disease.''<ref>Sierra, F. (2016). The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. ''Cold Spring Harbor perspectives in medicine'', ''6''(4), a025163.</ref> In contrast, the biology of aging research field (biogerontology) views the mechanisms of aging as the root cause of most of society’s most prevalent, costly, and debilitating diseases.<ref name=":2">[https://www.nature.com/articles/s41586-019-1365-2 Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. ''Nature'', ''571''(7764), 183-192.]</ref><ref name=":14">[[Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. Nature Reviews Drug Discovery, 19(8), 513-532.\|Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]]</ref><ref name=":3">[[Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. Aging cell, 14(4), 497-510.\|Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. ''Aging cell'', ''14''(4), 497-510.]]</ref>

	In 2018, for the first time in human history, the number of people aged over 64 became greater than those aged under 5.<ref name=":32" /> This disparity is projected to ~~only~~ widen ~~further~~ with a rapidly aging population.<ref name=":32">Ritchie, H., & Roser, M. (2019). Age structure. ''Our World in Data''.</ref> The clear implications for a substantial increase in age-related disease burden has led to urgent calls from scientists for global society to support aging biology research to increase healthy life expectancy.<ref name=":3" /><ref>[[Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. Science translational medicine, 2(40), 40cm21-40cm21.\|Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. ''Science translational medicine'', ''2''(40), 40cm21-40cm21.]]</ref>		In 2018, for the first time in human history, the number of people aged over 64 became greater than those aged under 5.<ref name=":32" /> This disparity is projected to widen with a rapidly aging population.<ref name=":32">Ritchie, H., & Roser, M. (2019). Age structure. ''Our World in Data''.</ref> The clear implications for a substantial increase in age-related disease burden has led to urgent calls from scientists for global society to support aging biology research to increase healthy life expectancy.<ref name=":3" /><ref>[[Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. Science translational medicine, 2(40), 40cm21-40cm21.\|Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. ''Science translational medicine'', ''2''(40), 40cm21-40cm21.]]</ref>

	== What is aging? ==		== What is aging? ==

Geroscientist: /* Dietary restriction mimetics and mTOR inhibitors */

2024-07-21T12:30:03Z

Dietary restriction mimetics and mTOR inhibitors

← Older revision		Revision as of 12:30, 21 July 2024
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	[[File:Updated deaths and aging.png\|alt=\|thumb\|618x618px\|Incidence of all age-related diseases increases exponentially with increasing age]]		[[File:Updated deaths and aging.png\|alt=\|thumb\|618x618px\|Incidence of all age-related diseases increases exponentially with increasing age]]
	People have yearned for the fountain of youth all throughout history. However, until recently, there has ~~yet to exist~~ a concerted research effort ~~for actualizing this at a societal level~~. In the modern era, humanity ~~is supportive of~~ research towards the cure of age-related diseases (e.g. Alzheimer’s, heart disease, and [[Aging and Cancer\|most cancers]]) – a desire present at every level of human ~~organisation~~ that spans across individuals, communities, and society. This reflects a core human desire to be healthy. Yet, recognizing that humanity should strive towards a cure for aging is a sentiment that does not attract such widespread popularity.		People have yearned for the fountain of youth all throughout history. However, until recently, there has not been a concerted research effort to address the aging of cells, tissues and and organs. In the modern era, humanity supports research towards the cure of age-related diseases (e.g. Alzheimer’s, heart disease, and [[Aging and Cancer\|most cancers]]) – a desire present at every level of human organization that spans across individuals, communities, and society. This reflects a core human desire to be healthy. Yet, recognizing that humanity should strive towards a cure for aging is a sentiment that does not attract such widespread popularity.

	Lack of societal support stems from two fundamental misconceptions – that ‘aging’ merely represents the natural chronological passage of time, and that aging is an entirely separate category from ''age-related disease.''<ref>Sierra, F. (2016). The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. ''Cold Spring Harbor perspectives in medicine'', ''6''(4), a025163.</ref> In contrast, the biology of aging research field (biogerontology) understands the mechanisms of aging as the root cause of most of society’s most prevalent, costly, and debilitating diseases.<ref name=":2">[https://www.nature.com/articles/s41586-019-1365-2 Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. ''Nature'', ''571''(7764), 183-192.]</ref><ref name=":14">[[Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. Nature Reviews Drug Discovery, 19(8), 513-532.\|Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]]</ref><ref name=":3">[[Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. Aging cell, 14(4), 497-510.\|Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. ''Aging cell'', ''14''(4), 497-510.]]</ref>		Lack of societal support stems from two fundamental misconceptions – that ‘aging’ merely represents the natural chronological passage of time, and that aging is an entirely separate category from ''age-related disease.''<ref>Sierra, F. (2016). The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. ''Cold Spring Harbor perspectives in medicine'', ''6''(4), a025163.</ref> In contrast, the biology of aging research field (biogerontology) understands the mechanisms of aging as the root cause of most of society’s most prevalent, costly, and debilitating diseases.<ref name=":2">[https://www.nature.com/articles/s41586-019-1365-2 Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. ''Nature'', ''571''(7764), 183-192.]</ref><ref name=":14">[[Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. Nature Reviews Drug Discovery, 19(8), 513-532.\|Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]]</ref><ref name=":3">[[Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. Aging cell, 14(4), 497-510.\|Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. ''Aging cell'', ''14''(4), 497-510.]]</ref>
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	Using epigenetic reprogramming in ''naturally aged'' mice has more recently been shown to improve memory/cognition, promote muscle regeneration, and restore vision.<ref>Wang, C., Ros, R. R., Martinez-Redondo, P., Ma, Z., Shi, L., Xue, Y., ... & Belmonte, J. C. I. (2021). In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. ''Nature Communications'', ''12''(1), 1-15.</ref><ref>Rodríguez-Matellán, A., Alcazar, N., Hernández, F., Serrano, M., & Ávila, J. (2020). In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice. ''Stem cell reports'', ''15''(5), 1056-1066.</ref><ref name=":16" /> It has been envisioned by some scientists as a therapy that could be used periodically, perhaps every few decades, to continually reverse aging in humans. However, evidence for a truly comprehensive reversal of aging via partial reprogramming in mice, let alone in humans, is lacking. Whether reprogramming based strategies will extend healthy lifespan in normally aged mice is not currently well studied.		Using epigenetic reprogramming in ''naturally aged'' mice has more recently been shown to improve memory/cognition, promote muscle regeneration, and restore vision.<ref>Wang, C., Ros, R. R., Martinez-Redondo, P., Ma, Z., Shi, L., Xue, Y., ... & Belmonte, J. C. I. (2021). In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. ''Nature Communications'', ''12''(1), 1-15.</ref><ref>Rodríguez-Matellán, A., Alcazar, N., Hernández, F., Serrano, M., & Ávila, J. (2020). In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice. ''Stem cell reports'', ''15''(5), 1056-1066.</ref><ref name=":16" /> It has been envisioned by some scientists as a therapy that could be used periodically, perhaps every few decades, to continually reverse aging in humans. However, evidence for a truly comprehensive reversal of aging via partial reprogramming in mice, let alone in humans, is lacking. Whether reprogramming based strategies will extend healthy lifespan in normally aged mice is not currently well studied.
	=== Dietary restriction mimetics and [[mTOR]] inhibitors ===		=== Dietary restriction mimetics and mTOR inhibitors ===
	Dietary restriction (DR) has consistently been shown to extend healthy lifespan in animals ranging from worms, to mice, and to primates.<ref>Fontana, L., Partridge, L., & Longo, V. D. (2010). Extending healthy life span—from yeast to humans. ''science'', ''328''(5976), 321-326.</ref><ref>Speakman, J. R., & Mitchell, S. E. (2011). Caloric restriction. ''Molecular aspects of medicine'', ''32''(3), 159-221.</ref> In animals, DR leads to significant improvement to healthy lifespan; however, the proportional lifespan benefit generally declines with increasing species size/complexity.<ref name=":24">Katewa, S. D., & Kapahi, P. (2010). Dietary restriction and aging, 2009. ''Aging cell'', ''9''(2), 105-112.</ref><ref name=":25">Selman, C. (2014). Dietary restriction and the pursuit of effective mimetics. ''Proceedings of the Nutrition Society'', ''73''(2), 260-270.</ref> Like many therapies that target aging, the effect of DR is not consistent across different studies for various reasons.<ref name=":26">Unnikrishnan, A., Matyi, S., Garrett, K., Ranjo‐Bishop, M., Allison, D. B., Ejima, K., ... & Richardson, A. (2021). Reevaluation of the effect of dietary restriction on different recombinant inbred lines of male and female mice. Aging Cell, e13500.</ref><ref name=":27">Liao, C. Y., Rikke, B. A., Johnson, T. E., Diaz, V., & Nelson, J. F. (2010). Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. ''Aging cell'', ''9''(1), 92-95.</ref> This is often due to genetic factors, such as several studies showing that while certain strains of mice subjected to DR live longer, other strains show no benefit or even lifespan detriment.<ref name=":26" /><ref name=":27" /> Other reasons may be related to environmental differences, or DR extent or diet composition in DR diets used in these experiments.		Dietary restriction (DR) has consistently been shown to extend healthy lifespan in animals ranging from worms, to mice, and to primates.<ref>Fontana, L., Partridge, L., & Longo, V. D. (2010). Extending healthy life span—from yeast to humans. ''science'', ''328''(5976), 321-326.</ref><ref>Speakman, J. R., & Mitchell, S. E. (2011). Caloric restriction. ''Molecular aspects of medicine'', ''32''(3), 159-221.</ref> In animals, DR leads to significant improvement to healthy lifespan; however, the proportional lifespan benefit generally declines with increasing species size/complexity.<ref name=":24">Katewa, S. D., & Kapahi, P. (2010). Dietary restriction and aging, 2009. ''Aging cell'', ''9''(2), 105-112.</ref><ref name=":25">Selman, C. (2014). Dietary restriction and the pursuit of effective mimetics. ''Proceedings of the Nutrition Society'', ''73''(2), 260-270.</ref> Like many therapies that target aging, the effect of DR is not consistent across different studies for various reasons.<ref name=":26">Unnikrishnan, A., Matyi, S., Garrett, K., Ranjo‐Bishop, M., Allison, D. B., Ejima, K., ... & Richardson, A. (2021). Reevaluation of the effect of dietary restriction on different recombinant inbred lines of male and female mice. Aging Cell, e13500.</ref><ref name=":27">Liao, C. Y., Rikke, B. A., Johnson, T. E., Diaz, V., & Nelson, J. F. (2010). Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. ''Aging cell'', ''9''(1), 92-95.</ref> This is often due to genetic factors, such as several studies showing that while certain strains of mice subjected to DR live longer, other strains show no benefit or even lifespan detriment.<ref name=":26" /><ref name=":27" /> Other reasons may be related to environmental differences, or DR extent or diet composition in DR diets used in these experiments.

	Dysregulation of nutrient-sensing is regarded as a hallmark of aging, playing a key role in the aging process.<ref name=":13" /> Relevant metabolic pathways such as IGF-1, mTOR and AMPK, are influenced by DR in extending healthy lifespan in animals.<ref>de Cabo, R., & Mattson, M. P. (2019). Effects of intermittent fasting on health, aging, and disease. ''New England Journal of Medicine'', ''381''(26), 2541-2551.</ref>		Dysregulation of nutrient-sensing is regarded as a hallmark of aging, playing a key role in the aging process.<ref name=":13" /> Relevant metabolic pathways such as IGF-1, [[mTOR]] and AMPK, are influenced by DR in extending healthy lifespan in animals.<ref>de Cabo, R., & Mattson, M. P. (2019). Effects of intermittent fasting on health, aging, and disease. ''New England Journal of Medicine'', ''381''(26), 2541-2551.</ref>

	Given the difficulty of implementing DR as medicine for humans, due to difficulty with patient adherence, drugs that mimic the effects of dietary restriction are being developed.<ref name=":25" /> Similarly, there is a significant and ongoing research effort that aims to determine whether intermittent fasting or time restricted eating may capture some of the potential health benefits of DR, while being easier for patients to adhere to.<ref name=":24" /> There is generally a lack of evidence in human clinical trials in justifying the use of these lifestyle interventions for slowing aging in healthy adults.<ref>Lee, M. B., Hill, C. M., Bitto, A., & Kaeberlein, M. (2021). Antiaging diets: Separating fact from fiction. ''Science'', ''374''(6570), eabe7365.</ref>		Given the difficulty of implementing DR as medicine for humans, due to difficulty with patient adherence, drugs that mimic the effects of dietary restriction are being developed.<ref name=":25" /> Similarly, there is a significant and ongoing research effort that aims to determine whether intermittent fasting or time restricted eating may capture some of the potential health benefits of DR, while being easier for patients to adhere to.<ref name=":24" /> There is generally a lack of evidence in human clinical trials in justifying the use of these lifestyle interventions for slowing aging in healthy adults.<ref>Lee, M. B., Hill, C. M., Bitto, A., & Kaeberlein, M. (2021). Antiaging diets: Separating fact from fiction. ''Science'', ''374''(6570), eabe7365.</ref>

Geroscientist: /* Epigenetic reprogramming */

2024-07-21T12:25:02Z

Epigenetic reprogramming

← Older revision		Revision as of 12:25, 21 July 2024
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	Recent experimental breakthroughs have provided early evidence that aspects of aging can be reversed,<ref name=":15">[[Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., ... & Belmonte, J. C. I. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell, 167(7), 1719-1733.\|Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., ... & Belmonte, J. C. I. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. ''Cell'', ''167''(7), 1719-1733.]]</ref><ref name=":16">Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH. Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020 Dec;588(7836):124-9.		Recent experimental breakthroughs have provided early evidence that aspects of aging can be reversed,<ref name=":15">[[Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., ... & Belmonte, J. C. I. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell, 167(7), 1719-1733.\|Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., ... & Belmonte, J. C. I. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. ''Cell'', ''167''(7), 1719-1733.]]</ref><ref name=":16">Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH. Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020 Dec;588(7836):124-9.

	https://www.nature.com/articles/s41586-020-2975-4</ref> ~~further~~ challenging old assumptions ~~about~~ aging simply ~~being~~ a result of ~~chronological~~ time.[[File:ONH regeneration epigenetic reprogramming.png\|center\|frame\|In vivo epigenetic reprogramming can lead to regeneration of the optic nerve in injury and glaucoma mouse models, and lead to visual recovery in natural aging]]		https://www.nature.com/articles/s41586-020-2975-4</ref> challenging old assumptions that aging is simply a result of time passing.[[File:ONH regeneration epigenetic reprogramming.png\|center\|frame\|In vivo epigenetic reprogramming can lead to regeneration of the optic nerve in injury and glaucoma mouse models, and lead to visual recovery in natural aging]]

	[[Epigenetic reprogramming]] is based on work that earnt [https://embryology.med.unsw.edu.au/embryology/index.php/Embryology_History_-_Shinya_Yamanaka Shinya Yamanaka] the 2012 Nobel Prize in Medicine. Yamanaka showed that it was possible to reprogram adult body cells back into biologically immortal pluripotent stem cells that are capable of turning into any cell of the body.<ref name=":17">Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. ''cell'', ''126''(4), 663-676.</ref><ref name=":18">Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. ''cell'', ''131''(5), 861-872.</ref> This was achieved by activating only four transcription factors - the [[Yamanaka factors\|''Yamanaka factors'']] - OCT4, SOX2, KLF4, and MYC (or OSKM).<ref name=":17" /><ref name=":18" />		[[Epigenetic reprogramming]] is based on work that earnt [https://embryology.med.unsw.edu.au/embryology/index.php/Embryology_History_-_Shinya_Yamanaka Shinya Yamanaka] the 2012 Nobel Prize in Medicine. Yamanaka showed that it was possible to reprogram adult body cells back into biologically immortal pluripotent stem cells that are capable of turning into any cell of the body.<ref name=":17">Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. ''cell'', ''126''(4), 663-676.</ref><ref name=":18">Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. ''cell'', ''131''(5), 861-872.</ref> This was achieved by activating only four transcription factors - the [[Yamanaka factors\|''Yamanaka factors'']] - OCT4, SOX2, KLF4, and MYC (or OSKM).<ref name=":17" /><ref name=":18" />

Dmitry Dzhagarov: /* Dietary restriction mimetics and mTOR inhibitors */

2024-06-19T16:29:21Z

Dietary restriction mimetics and mTOR inhibitors

← Older revision		Revision as of 16:29, 19 June 2024
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	Using epigenetic reprogramming in ''naturally aged'' mice has more recently been shown to improve memory/cognition, promote muscle regeneration, and restore vision.<ref>Wang, C., Ros, R. R., Martinez-Redondo, P., Ma, Z., Shi, L., Xue, Y., ... & Belmonte, J. C. I. (2021). In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. ''Nature Communications'', ''12''(1), 1-15.</ref><ref>Rodríguez-Matellán, A., Alcazar, N., Hernández, F., Serrano, M., & Ávila, J. (2020). In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice. ''Stem cell reports'', ''15''(5), 1056-1066.</ref><ref name=":16" /> It has been envisioned by some scientists as a therapy that could be used periodically, perhaps every few decades, to continually reverse aging in humans. However, evidence for a truly comprehensive reversal of aging via partial reprogramming in mice, let alone in humans, is lacking. Whether reprogramming based strategies will extend healthy lifespan in normally aged mice is not currently well studied.		Using epigenetic reprogramming in ''naturally aged'' mice has more recently been shown to improve memory/cognition, promote muscle regeneration, and restore vision.<ref>Wang, C., Ros, R. R., Martinez-Redondo, P., Ma, Z., Shi, L., Xue, Y., ... & Belmonte, J. C. I. (2021). In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. ''Nature Communications'', ''12''(1), 1-15.</ref><ref>Rodríguez-Matellán, A., Alcazar, N., Hernández, F., Serrano, M., & Ávila, J. (2020). In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice. ''Stem cell reports'', ''15''(5), 1056-1066.</ref><ref name=":16" /> It has been envisioned by some scientists as a therapy that could be used periodically, perhaps every few decades, to continually reverse aging in humans. However, evidence for a truly comprehensive reversal of aging via partial reprogramming in mice, let alone in humans, is lacking. Whether reprogramming based strategies will extend healthy lifespan in normally aged mice is not currently well studied.
	=== Dietary restriction mimetics and mTOR inhibitors ===		=== Dietary restriction mimetics and [[mTOR]] inhibitors ===
	Dietary restriction (DR) has consistently been shown to extend healthy lifespan in animals ranging from worms, to mice, and to primates.<ref>Fontana, L., Partridge, L., & Longo, V. D. (2010). Extending healthy life span—from yeast to humans. ''science'', ''328''(5976), 321-326.</ref><ref>Speakman, J. R., & Mitchell, S. E. (2011). Caloric restriction. ''Molecular aspects of medicine'', ''32''(3), 159-221.</ref> In animals, DR leads to significant improvement to healthy lifespan; however, the proportional lifespan benefit generally declines with increasing species size/complexity.<ref name=":24">Katewa, S. D., & Kapahi, P. (2010). Dietary restriction and aging, 2009. ''Aging cell'', ''9''(2), 105-112.</ref><ref name=":25">Selman, C. (2014). Dietary restriction and the pursuit of effective mimetics. ''Proceedings of the Nutrition Society'', ''73''(2), 260-270.</ref> Like many therapies that target aging, the effect of DR is not consistent across different studies for various reasons.<ref name=":26">Unnikrishnan, A., Matyi, S., Garrett, K., Ranjo‐Bishop, M., Allison, D. B., Ejima, K., ... & Richardson, A. (2021). Reevaluation of the effect of dietary restriction on different recombinant inbred lines of male and female mice. Aging Cell, e13500.</ref><ref name=":27">Liao, C. Y., Rikke, B. A., Johnson, T. E., Diaz, V., & Nelson, J. F. (2010). Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. ''Aging cell'', ''9''(1), 92-95.</ref> This is often due to genetic factors, such as several studies showing that while certain strains of mice subjected to DR live longer, other strains show no benefit or even lifespan detriment.<ref name=":26" /><ref name=":27" /> Other reasons may be related to environmental differences, or DR extent or diet composition in DR diets used in these experiments.		Dietary restriction (DR) has consistently been shown to extend healthy lifespan in animals ranging from worms, to mice, and to primates.<ref>Fontana, L., Partridge, L., & Longo, V. D. (2010). Extending healthy life span—from yeast to humans. ''science'', ''328''(5976), 321-326.</ref><ref>Speakman, J. R., & Mitchell, S. E. (2011). Caloric restriction. ''Molecular aspects of medicine'', ''32''(3), 159-221.</ref> In animals, DR leads to significant improvement to healthy lifespan; however, the proportional lifespan benefit generally declines with increasing species size/complexity.<ref name=":24">Katewa, S. D., & Kapahi, P. (2010). Dietary restriction and aging, 2009. ''Aging cell'', ''9''(2), 105-112.</ref><ref name=":25">Selman, C. (2014). Dietary restriction and the pursuit of effective mimetics. ''Proceedings of the Nutrition Society'', ''73''(2), 260-270.</ref> Like many therapies that target aging, the effect of DR is not consistent across different studies for various reasons.<ref name=":26">Unnikrishnan, A., Matyi, S., Garrett, K., Ranjo‐Bishop, M., Allison, D. B., Ejima, K., ... & Richardson, A. (2021). Reevaluation of the effect of dietary restriction on different recombinant inbred lines of male and female mice. Aging Cell, e13500.</ref><ref name=":27">Liao, C. Y., Rikke, B. A., Johnson, T. E., Diaz, V., & Nelson, J. F. (2010). Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. ''Aging cell'', ''9''(1), 92-95.</ref> This is often due to genetic factors, such as several studies showing that while certain strains of mice subjected to DR live longer, other strains show no benefit or even lifespan detriment.<ref name=":26" /><ref name=":27" /> Other reasons may be related to environmental differences, or DR extent or diet composition in DR diets used in these experiments.

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	Among the hundreds of interventions studied within geroscience research, rapamycin is unique in its highly consistent and reproducible effect on healthy lifespan extension in mice.<ref>Johnson, S. C., Martin, G. M., Rabinovitch, P. S., & Kaeberlein, M. (2013). Preserving youth: does rapamycin deliver?. ''Science translational medicine'', ''5''(211), 211fs40.</ref> It is also the drug that exhibits the largest lifespan effect extension in multiple strains of mice, both when dosed in early life and at old age.<ref>Johnson, S. C., Martin, G. M., Rabinovitch, P. S., & Kaeberlein, M. (2013). Preserving youth: does rapamycin deliver?. ''Science translational medicine'', ''5''(211), 211fs40.</ref><ref>Kaeberlein, M. (2014). Rapamycin and aging: when, for how long, and how much? ''Journal of genetics and genomics'', ''41''(9), 459.</ref> Rapamycin is being repurposed for humans as an anti-aging drug, such as in the PEARL clinical study, which is expected to provide preliminary results in 2023.<ref>[https://clinicaltrials.gov/ct2/show/NCT04488601 ''Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study - Full Text View - ClinicalTrials.gov''. Clinicaltrials.gov. (2021). Retrieved 27 May 2021, from https://clinicaltrials.gov/ct2/show/NCT04488601.]</ref>		Among the hundreds of interventions studied within geroscience research, rapamycin is unique in its highly consistent and reproducible effect on healthy lifespan extension in mice.<ref>Johnson, S. C., Martin, G. M., Rabinovitch, P. S., & Kaeberlein, M. (2013). Preserving youth: does rapamycin deliver?. ''Science translational medicine'', ''5''(211), 211fs40.</ref> It is also the drug that exhibits the largest lifespan effect extension in multiple strains of mice, both when dosed in early life and at old age.<ref>Johnson, S. C., Martin, G. M., Rabinovitch, P. S., & Kaeberlein, M. (2013). Preserving youth: does rapamycin deliver?. ''Science translational medicine'', ''5''(211), 211fs40.</ref><ref>Kaeberlein, M. (2014). Rapamycin and aging: when, for how long, and how much? ''Journal of genetics and genomics'', ''41''(9), 459.</ref> Rapamycin is being repurposed for humans as an anti-aging drug, such as in the PEARL clinical study, which is expected to provide preliminary results in 2023.<ref>[https://clinicaltrials.gov/ct2/show/NCT04488601 ''Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study - Full Text View - ClinicalTrials.gov''. Clinicaltrials.gov. (2021). Retrieved 27 May 2021, from https://clinicaltrials.gov/ct2/show/NCT04488601.]</ref>

	=== The link between lifespan and aging ===		=== The link between lifespan and aging ===
	*Lifespan can range from mere days in mayflies, to several years in dogs, and up to centuries in bowhead whales<ref>[[Ogden, L. E. (2019). Travels through Time. BioScience, 69(11), 860-866.\|Ogden, L. E. (2019). Travels through Time. ''BioScience'', ''69''(11), 860-866.]]</ref>		*Lifespan can range from mere days in mayflies, to several years in dogs, and up to centuries in bowhead whales<ref>[[Ogden, L. E. (2019). Travels through Time. BioScience, 69(11), 860-866.\|Ogden, L. E. (2019). Travels through Time. ''BioScience'', ''69''(11), 860-866.]]</ref>

Dmitry Dzhagarov: /* Traditional risk factors and heart disease */

2023-05-10T20:56:48Z

Traditional risk factors and heart disease

← Older revision		Revision as of 20:56, 10 May 2023
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	==== Traditional risk factors and heart disease ====		==== Traditional risk factors and heart disease ====
	[[File:CVD 1st Risk Factor .png\|alt=Aging dwarfs all other risk factors for heart disease\|center\|thumb\|933x933px\|Aging dwarfs all other risk factors for heart disease - suggesting a central role - yet remains an unexplored target for drug development]]		[[File:CVD 1st Risk Factor .png\|alt=Aging dwarfs all other risk factors for heart disease\|center\|thumb\|933x933px\|Aging dwarfs all other risk factors for heart disease - suggesting a central role - yet remains an unexplored target for drug development]]
	Hypertension, smoking, and cholesterol are examples of well-known heart disease risk factors that have been used by scientists/physicians to guide the research and development of effective therapies. This strategy originated from the Framingham Heart Study – an initiative spanning decades that observed thousands of people to understand what genetic and environmental factors influence heart disease.<ref>Mahmooda, S. S., Levy, D., Vasan, R. S., & Wang, T. J. (2014). The Framingham Heart Study and the epidemiology of cardiovascular diseases: A historical perspective. ''Lancet'', ''383''(9921), 999-1008.</ref>The resulting risk factor paradigm has since been adopted across all domains of disease in biomedical research, and is core to the practice of clinical medicine		[[File:Aging & CVD.jpg\|left\|thumb\|Aging as an etiological cause of cardiovascular disease (CVD). Age-associated cardiovascular (CV) dysfunction is a key antecedent to the development of CV disease (CVD). CV dysfunction with aging is characterized by impaired vascular endothelial function and stiffening of the large elastic arteries, each of which is an independent predictor of CVD. These processes are largely mediated by an excess production of reactive oxygen species (ROS) and an increase in chronic, low-grade inflammation (inflammaging) that ultimately leads to a reduction in bioavailability of the vasodilatory molecule nitric oxide.<ref>Murray, K. O., Mahoney, S. A., Venkatasubramanian, R., Seals, D. R., & Clayton, Z. S. (2023). Aging, aerobic exercise, and cardiovascular health: Barriers, alternative strategies and future directions. Experimental gerontology, 173, 112105.PMID: 36731386 PMC:[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068966/ 10068966] DOI: 10.1016/j.exger.2023.112105</ref>]]
			Hypertension, smoking, and cholesterol are examples of well-known heart disease risk factors that have been used by scientists/physicians to guide the research and development of effective therapies. This strategy originated from the Framingham Heart Study – an initiative spanning decades that observed thousands of people to understand what genetic and environmental factors influence heart disease.<ref>Mahmooda, S. S., Levy, D., Vasan, R. S., & Wang, T. J. (2014). The Framingham Heart Study and the epidemiology of cardiovascular diseases: A historical perspective. ''Lancet'', ''383''(9921), 999-1008.</ref>The resulting risk factor paradigm has since been adopted across all domains of disease in biomedical research, and is core to the practice of clinical medicine
	Coordinated research efforts have helped identify genetic and environmental factors important to heart disease risk. Identifying whether risk factors are modifiable enables the development of effective therapeutics, such as for the prevention of cardiovascular diseases. For example, identifying high blood pressure and cholesterol as modifiable risk factors has since led to anti-hypertensive and cholesterol medications being among the most commonly prescribed drugs across the world.<ref>Hajar, R. (2016). Framingham contribution to cardiovascular disease. ''Heart views: the official journal of the Gulf Heart Association'', ''17''(2), 78.</ref> Aging is widely accepted among physicians and biomedical scientists as the greatest risk factor for almost all the major diseases in developed countries.<ref>Kaeberlein, M., Rabinovitch, P. S., & Martin, G. M. (2015). Healthy aging: the ultimate preventative medicine. ''Science'', ''350''(6265), 1191-1193.</ref> However, aging is also traditionally viewed as a risk factor that cannot be modified. Unmodifiable risk factors are regarded as unimportant for the development of interventions. The prevailing assumption that aging is an unmodifiable risk factor is now being challenged by biogerontology researchers.<ref>Olshansky, S. J. (2015). Has the rate of human aging already been modified?. ''Cold Spring Harbor perspectives in medicine'', ''5''(12), a025965.		Coordinated research efforts have helped identify genetic and environmental factors important to heart disease risk. Identifying whether risk factors are modifiable enables the development of effective therapeutics, such as for the prevention of cardiovascular diseases. For example, identifying high blood pressure and cholesterol as modifiable risk factors has since led to anti-hypertensive and cholesterol medications being among the most commonly prescribed drugs across the world.<ref>Hajar, R. (2016). Framingham contribution to cardiovascular disease. ''Heart views: the official journal of the Gulf Heart Association'', ''17''(2), 78.</ref> Aging is widely accepted among physicians and biomedical scientists as the greatest risk factor for almost all the major diseases in developed countries.<ref>Kaeberlein, M., Rabinovitch, P. S., & Martin, G. M. (2015). Healthy aging: the ultimate preventative medicine. ''Science'', ''350''(6265), 1191-1193.</ref> However, aging is also traditionally viewed as a risk factor that cannot be modified. Unmodifiable risk factors are regarded as unimportant for the development of interventions. The prevailing assumption that aging is an unmodifiable risk factor is now being challenged by biogerontology researchers.<ref>Olshansky, S. J. (2015). Has the rate of human aging already been modified?. ''Cold Spring Harbor perspectives in medicine'', ''5''(12), a025965.

Geroscientist: /* What is aging? */

2023-01-29T10:01:37Z

What is aging?

← Older revision		Revision as of 10:01, 29 January 2023
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	==== Healthspan versus lifespan ====		==== Healthspan versus lifespan ====
	'''The concept of healthspan ~~describes~~ the period of life spent free from disease'''		'''The concept of healthspan refers to the period of life spent free from disease'''

	In the 21st Century, population healthspan contrasts significantly with lifespan. Although the latter has steadily increased over the last two centuries, the evidence strongly suggests that healthspan has not kept up with lifespan.<ref name=":0">[https://academic.oup.com/gerontologist/article/55/6/901/2605490?login=true Crimmins, E. M. (2015). Lifespan and healthspan: past, present, and promise. ''The Gerontologist'', ''55''(6), 901-911.]</ref>		In the 21st Century, population healthspan contrasts significantly with lifespan. Although the latter has steadily increased over the last two centuries, the evidence strongly suggests that healthspan has not kept up with lifespan.<ref name=":0">[https://academic.oup.com/gerontologist/article/55/6/901/2605490?login=true Crimmins, E. M. (2015). Lifespan and healthspan: past, present, and promise. ''The Gerontologist'', ''55''(6), 901-911.]</ref>
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	Aging is often regarded as a natural and universal fact of life. In medicine, physicians are tasked with the need to classify whether the patient in front of them has a disease or not. This is a necessary part of the current approach of disease-centric medicine, because a binary decision is made to determine whether treatment is necessary. Under this paradigm, age-related changes not regarded as outright disease may be deemed normal, and so further management is not necessary. Such change with age may be related to function, such as declines in grip strength or exercise capacity; or physiological, such as increased low-grade systemic inflammation.<ref>Hubbard, R. E., O’Mahony, M. S., Savva, G. M., Calver, B. L., & Woodhouse, K. W. (2009). Inflammation and frailty measures in older people. ''Journal of cellular and molecular medicine'', ''13''(9b), 3103-3109.</ref><ref>Leng, S. X., Xue, Q. L., Tian, J., Walston, J. D., & Fried, L. P. (2007). Inflammation and frailty in older women. ''Journal of the American Geriatrics Society'', ''55''(6), 864-871.</ref> What may be regarded as normal or healthy in clinical practice is also typically compared to chronological age, i.e. being healthy for one's age. This can neglect the reality that a healthy 60 year old is functionally impaired compared to the average 20 year old.<ref>Kaeberlein, M. (2019). It is time to embrace 21st-century medicine. ''public policy & aging report'', 29(4), 111-115</ref>		Aging is often regarded as a natural and universal fact of life. In medicine, physicians are tasked with the need to classify whether the patient in front of them has a disease or not. This is a necessary part of the current approach of disease-centric medicine, because a binary decision is made to determine whether treatment is necessary. Under this paradigm, age-related changes not regarded as outright disease may be deemed normal, and so further management is not necessary. Such change with age may be related to function, such as declines in grip strength or exercise capacity; or physiological, such as increased low-grade systemic inflammation.<ref>Hubbard, R. E., O’Mahony, M. S., Savva, G. M., Calver, B. L., & Woodhouse, K. W. (2009). Inflammation and frailty measures in older people. ''Journal of cellular and molecular medicine'', ''13''(9b), 3103-3109.</ref><ref>Leng, S. X., Xue, Q. L., Tian, J., Walston, J. D., & Fried, L. P. (2007). Inflammation and frailty in older women. ''Journal of the American Geriatrics Society'', ''55''(6), 864-871.</ref> What may be regarded as normal or healthy in clinical practice is also typically compared to chronological age, i.e. being healthy for one's age. This can neglect the reality that a healthy 60 year old is functionally impaired compared to the average 20 year old.<ref>Kaeberlein, M. (2019). It is time to embrace 21st-century medicine. ''public policy & aging report'', 29(4), 111-115</ref>

	====== ~~'''~~Lack of consensus on what defines aging~~'''~~ ======		====== Lack of consensus on what defines aging ======
	However, some level of collective confusion in meaning is prevalent among the public, physicians, and scientists. This is predominantly due to the imprecision of the word 'aging'. Even among aging biology researchers there is a lack of consensus as to what aging refers to.<ref name=":20" /> This remains a significant problem among scientists, and is regarded by some as a barrier to advancing the field into mainstream public consciousness. Yet, there is now consensus among geroscience researchers (the subfield of aging biology concerned with medicine) that aging mechanisms can be targeted to increase healthspan.		However, some level of collective confusion in meaning is prevalent among the public, physicians, and scientists. This is predominantly due to the imprecision of the word 'aging'. Even among aging biology researchers there is a lack of consensus as to what aging refers to.<ref name=":20" /> This remains a significant problem among scientists, and is regarded by some as a barrier to advancing the field into mainstream public consciousness. Yet, there is now consensus among geroscience researchers (the subfield of aging biology concerned with medicine) that aging mechanisms can be targeted to increase healthspan.

Geroscientist: /* Healthspan versus lifespan */

2023-01-29T09:59:36Z

Healthspan versus lifespan

← Older revision		Revision as of 09:59, 29 January 2023
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	A recent paper published by Professors at Harvard Medical School, Oxford University, and London Business School, estimated that a drug that slows aging by merely one year could add $US 38 trillion to the US economy.<ref name=":31">Scott, A. J., Ellison, M., & Sinclair, D. A. (2021). The economic value of targeting aging. ''Nature Aging'', ''1''(7), 616-623.</ref> This was justified by estimating how slowed aging can result in both improved health and longevity. The resultant increases in independence and productivity is subject to a virtuous cycle of further gains.<ref name=":31" /> This analysis highlights the profound difference between the current approach of targeting single diseases, versus targeting aging.		A recent paper published by Professors at Harvard Medical School, Oxford University, and London Business School, estimated that a drug that slows aging by merely one year could add $US 38 trillion to the US economy.<ref name=":31">Scott, A. J., Ellison, M., & Sinclair, D. A. (2021). The economic value of targeting aging. ''Nature Aging'', ''1''(7), 616-623.</ref> This was justified by estimating how slowed aging can result in both improved health and longevity. The resultant increases in independence and productivity is subject to a virtuous cycle of further gains.<ref name=":31" /> This analysis highlights the profound difference between the current approach of targeting single diseases, versus targeting aging.

	==== ~~'''~~Healthspan versus lifespan~~'''~~ ====		==== Healthspan versus lifespan ====
	'''The concept of healthspan describes the period of life spent free from disease'''		'''The concept of healthspan describes the period of life spent free from disease'''

Geroscientist at 09:59, 29 January 2023

2023-01-29T09:59:04Z

← Older revision		Revision as of 09:59, 29 January 2023
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	Lack of societal support stems from two fundamental misconceptions – that ‘aging’ merely represents the natural chronological passage of time, and that aging is an entirely separate category from ''age-related disease.''<ref>Sierra, F. (2016). The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. ''Cold Spring Harbor perspectives in medicine'', ''6''(4), a025163.</ref> In contrast, the biology of aging research field (biogerontology) understands the mechanisms of aging as the root cause of most of society’s most prevalent, costly, and debilitating diseases.<ref name=":2">[https://www.nature.com/articles/s41586-019-1365-2 Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. ''Nature'', ''571''(7764), 183-192.]</ref><ref name=":14">[[Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. Nature Reviews Drug Discovery, 19(8), 513-532.\|Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]]</ref><ref name=":3">[[Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. Aging cell, 14(4), 497-510.\|Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. ''Aging cell'', ''14''(4), 497-510.]]</ref>		Lack of societal support stems from two fundamental misconceptions – that ‘aging’ merely represents the natural chronological passage of time, and that aging is an entirely separate category from ''age-related disease.''<ref>Sierra, F. (2016). The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. ''Cold Spring Harbor perspectives in medicine'', ''6''(4), a025163.</ref> In contrast, the biology of aging research field (biogerontology) understands the mechanisms of aging as the root cause of most of society’s most prevalent, costly, and debilitating diseases.<ref name=":2">[https://www.nature.com/articles/s41586-019-1365-2 Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. ''Nature'', ''571''(7764), 183-192.]</ref><ref name=":14">[[Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. Nature Reviews Drug Discovery, 19(8), 513-532.\|Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]]</ref><ref name=":3">[[Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. Aging cell, 14(4), 497-510.\|Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. ''Aging cell'', ''14''(4), 497-510.]]</ref>

	In 2018, for the first time in human history, the number of people aged over 64 became greater than those aged under 5. This disparity is projected to only widen further with a rapidly aging population.<ref>Ritchie, H., & Roser, M. (2019). Age structure. ''Our World in Data''.</ref> The clear implications for a substantial increase in age-related disease burden has led to urgent calls from scientists for global society to support aging biology research to increase healthy life expectancy.<ref name=":3" /><ref>[[Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. Science translational medicine, 2(40), 40cm21-40cm21.\|Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. ''Science translational medicine'', ''2''(40), 40cm21-40cm21.]]</ref>		In 2018, for the first time in human history, the number of people aged over 64 became greater than those aged under 5.<ref name=":32" /> This disparity is projected to only widen further with a rapidly aging population.<ref name=":32">Ritchie, H., & Roser, M. (2019). Age structure. ''Our World in Data''.</ref> The clear implications for a substantial increase in age-related disease burden has led to urgent calls from scientists for global society to support aging biology research to increase healthy life expectancy.<ref name=":3" /><ref>[[Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. Science translational medicine, 2(40), 40cm21-40cm21.\|Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. ''Science translational medicine'', ''2''(40), 40cm21-40cm21.]]</ref>

	== What is aging? ==		== What is aging? ==

Geroscientist: /* Metformin */

2023-01-29T09:58:00Z

Metformin

← Older revision		Revision as of 09:58, 29 January 2023
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	Metformin extends healthy lifespan in worms, mice and rats.<ref>Song, J., Jiang, G., Zhang, J., Guo, J., Li, Z., Hao, K., ... & Dai, F. (2019). Metformin prolongs lifespan through remodeling the energy distribution strategy in silkworm, Bombyx mori. ''Aging (Albany NY)'', ''11''(1), 240.</ref><ref>Novelle, M. G., Ali, A., Diéguez, C., Bernier, M., & de Cabo, R. (2016). Metformin: a hopeful promise in aging research. ''Cold Spring Harbor perspectives in medicine'', ''6''(3), a025932.</ref> Metformin is one of the cheapest and most commonly prescribed medications in the world, and has been linked to lower incidence of cancer, heart disease, dementia, and mortality in patients with type 2 diabetes (T2DM).<ref name=":19">Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016). Metformin as a tool to target aging. ''Cell metabolism'', ''23''(6), 1060-1065.</ref>		Metformin extends healthy lifespan in worms, mice and rats.<ref>Song, J., Jiang, G., Zhang, J., Guo, J., Li, Z., Hao, K., ... & Dai, F. (2019). Metformin prolongs lifespan through remodeling the energy distribution strategy in silkworm, Bombyx mori. ''Aging (Albany NY)'', ''11''(1), 240.</ref><ref>Novelle, M. G., Ali, A., Diéguez, C., Bernier, M., & de Cabo, R. (2016). Metformin: a hopeful promise in aging research. ''Cold Spring Harbor perspectives in medicine'', ''6''(3), a025932.</ref> Metformin is one of the cheapest and most commonly prescribed medications in the world, and has been linked to lower incidence of cancer, heart disease, dementia, and mortality in patients with type 2 diabetes (T2DM).<ref name=":19">Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016). Metformin as a tool to target aging. ''Cell metabolism'', ''23''(6), 1060-1065.</ref>

	The Targeting Aging with Metformin (TAME) trial is investigating a drug with over 6 decades of human use, currently the first-line therapy for the age-related disease T2DM. One study suggested that despite the life-shortening effects of diabetes, T2DM patients on metformin, but not other medications, outlive those who are not diabetic.<ref>Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy, K. (2017). Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. ''Ageing Research Reviews'', ''40'', 31-44.</ref> As metformin has also shown healthspan and lifespan extension effects in naturally aging worms and mice, some researchers believe that it may slow aging.<ref name=":19" /> However, the data in humans is inconclusive without formal testing in a randomized clinical trial (RCT).		The Targeting Aging with Metformin (TAME) trial is investigating a drug with over 6 decades of human use, currently the first-line therapy for the age-related disease T2DM. One study suggested that despite the life-shortening effects of diabetes, T2DM patients on metformin, but not other medications, outlive those who are not diabetic.<ref>Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy, K. (2017). Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. ''Ageing Research Reviews'', ''40'', 31-44.</ref> As metformin has also shown healthspan and lifespan extension effects in naturally aging worms and mice, some researchers believe that it may slow aging.<ref name=":19" /> However, the data in humans is inconclusive without formal testing, such as in a randomized clinical trial (RCT).

	The Targeting Aging with Metformin (TAME) trial is a US, nation-wide, six-year RCT of over 3000 individuals aged 65 to 79.<ref name=":19" /> The goal is to investigate whether metformin will slow aging in humans, as it has been shown to extend healthspan in some animals. This will be measured by whether metformin can prevent the onset of multiple age-related diseases such as heart disease, cancer, and dementia.		The Targeting Aging with Metformin (TAME) trial is a US, nation-wide, six-year RCT of over 3000 individuals aged 65 to 79.<ref name=":19" /> The goal is to investigate whether metformin will slow aging in humans, as it has been shown to extend healthspan in some animals. This will be measured by whether metformin can prevent the onset of multiple age-related diseases such as heart disease, cancer, and dementia.

Geroscientist: /* Metformin */

2023-01-29T09:57:26Z

Metformin

← Older revision		Revision as of 09:57, 29 January 2023
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	Metformin extends healthy lifespan in worms, mice and rats.<ref>Song, J., Jiang, G., Zhang, J., Guo, J., Li, Z., Hao, K., ... & Dai, F. (2019). Metformin prolongs lifespan through remodeling the energy distribution strategy in silkworm, Bombyx mori. ''Aging (Albany NY)'', ''11''(1), 240.</ref><ref>Novelle, M. G., Ali, A., Diéguez, C., Bernier, M., & de Cabo, R. (2016). Metformin: a hopeful promise in aging research. ''Cold Spring Harbor perspectives in medicine'', ''6''(3), a025932.</ref> Metformin is one of the cheapest and most commonly prescribed medications in the world, and has been linked to lower incidence of cancer, heart disease, dementia, and mortality in patients with type 2 diabetes (T2DM).<ref name=":19">Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016). Metformin as a tool to target aging. ''Cell metabolism'', ''23''(6), 1060-1065.</ref>		Metformin extends healthy lifespan in worms, mice and rats.<ref>Song, J., Jiang, G., Zhang, J., Guo, J., Li, Z., Hao, K., ... & Dai, F. (2019). Metformin prolongs lifespan through remodeling the energy distribution strategy in silkworm, Bombyx mori. ''Aging (Albany NY)'', ''11''(1), 240.</ref><ref>Novelle, M. G., Ali, A., Diéguez, C., Bernier, M., & de Cabo, R. (2016). Metformin: a hopeful promise in aging research. ''Cold Spring Harbor perspectives in medicine'', ''6''(3), a025932.</ref> Metformin is one of the cheapest and most commonly prescribed medications in the world, and has been linked to lower incidence of cancer, heart disease, dementia, and mortality in patients with type 2 diabetes (T2DM).<ref name=":19">Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016). Metformin as a tool to target aging. ''Cell metabolism'', ''23''(6), 1060-1065.</ref>

	The Targeting Aging with Metformin (TAME) trial is investigating a drug with over 6 decades of human use, currently the first-line therapy for the age-related disease T2DM. One study suggested that despite the life-shortening effects of diabetes, T2DM patients on metformin, but not other medications, outlive those who are not diabetic.<ref>Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy, K. (2017). Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. ''Ageing Research Reviews'', ''40'', 31-44.</ref> As metformin has also shown healthspan and lifespan extension effects in naturally aging worms and mice, some researchers believe that it may slow aging.<ref name=":19" />		The Targeting Aging with Metformin (TAME) trial is investigating a drug with over 6 decades of human use, currently the first-line therapy for the age-related disease T2DM. One study suggested that despite the life-shortening effects of diabetes, T2DM patients on metformin, but not other medications, outlive those who are not diabetic.<ref>Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy, K. (2017). Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. ''Ageing Research Reviews'', ''40'', 31-44.</ref> As metformin has also shown healthspan and lifespan extension effects in naturally aging worms and mice, some researchers believe that it may slow aging.<ref name=":19" /> However, the data in humans is inconclusive without formal testing in a randomized clinical trial (RCT).

	The Targeting Aging with Metformin (TAME) trial is a US, nation-wide, six-year ~~clinical trial~~ of over 3000 individuals aged 65 to 79.<ref name=":19" /> The goal is to investigate whether metformin will slow aging in humans, as it has been shown to extend healthspan in some animals. This will be measured by whether metformin can prevent the onset of multiple age-related diseases such as heart disease, cancer, and dementia.		The Targeting Aging with Metformin (TAME) trial is a US, nation-wide, six-year RCT of over 3000 individuals aged 65 to 79.<ref name=":19" /> The goal is to investigate whether metformin will slow aging in humans, as it has been shown to extend healthspan in some animals. This will be measured by whether metformin can prevent the onset of multiple age-related diseases such as heart disease, cancer, and dementia.

	A key defining aspect in qualifying whether a drug targets aging (a gerotherapeutic or geroprotective drug), is the ability to delay or reverse the onset of multiple age-related diseases in tandem, to increase healthy lifespan.<ref>[https://www.nature.com/articles/s41573-020-0067-7 Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]</ref> The aging field continues to debate whether a geroprotector necessarily needs to increase healthspan, or both healthspan and lifespan.<ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869575/ Blagosklonny, M. V. (2021). The goal of geroscience is life extension. ''Oncotarget'', ''12''(3), 131.]</ref> Yet, what is clear now is that aging has a biology of critical relevance to the diseases associated with aging. This, along with multiple other lines of evidence across [[wikipedia:Biology\|biology]] and [[wikipedia:Epidemiology\|epidemiology]], suggest that the accumulation of multiple age-related diseases with time are not simply disparate processes or chance events that bear no relationship with one another. These diseases of older age, may in fact, be driven by an underlying aging process.<ref name=":2" /><ref name=":14" /><ref name=":3" />		A key defining aspect in qualifying whether a drug targets aging (a gerotherapeutic or geroprotective drug), is the ability to delay or reverse the onset of multiple age-related diseases in tandem, to increase healthy lifespan.<ref>[https://www.nature.com/articles/s41573-020-0067-7 Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]</ref> The aging field continues to debate whether a geroprotector necessarily needs to increase healthspan, or both healthspan and lifespan.<ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869575/ Blagosklonny, M. V. (2021). The goal of geroscience is life extension. ''Oncotarget'', ''12''(3), 131.]</ref> Yet, what is clear now is that aging has a biology of critical relevance to the diseases associated with aging. This, along with multiple other lines of evidence across [[wikipedia:Biology\|biology]] and [[wikipedia:Epidemiology\|epidemiology]], suggest that the accumulation of multiple age-related diseases with time are not simply disparate processes or chance events that bear no relationship with one another. These diseases of older age, may in fact, be driven by an underlying aging process.<ref name=":2" /><ref name=":14" /><ref name=":3" />

← Older revision		Revision as of 12:35, 21 July 2024
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	[[File:Updated deaths and aging.png\|alt=\|thumb\|618x618px\|Incidence of all age-related diseases increases exponentially with increasing age]]		[[File:Updated deaths and aging.png\|alt=\|thumb\|618x618px\|Incidence of all age-related diseases increases exponentially with increasing age]]
	People have yearned for the fountain of youth all throughout history. However, until recently, there has not been a concerted research effort to address ~~the~~ aging of ~~cells, tissues and and organs~~. In the modern era, humanity supports research towards the cure of age-related diseases (e.g. Alzheimer’s, heart disease, and [[Aging and Cancer\|most cancers]]) – a desire present at every level of human organization that spans across individuals, communities, and society. This reflects a core human desire to be healthy. Yet, recognizing that humanity should strive towards a cure for aging is a sentiment that does not attract such widespread popularity.		People have yearned for the fountain of youth all throughout history. However, until recently, there has not been a concerted research effort to address biological aging as a cause of disease. In the modern era, humanity supports research towards the cure of age-related diseases (e.g. Alzheimer’s, heart disease, and [[Aging and Cancer\|most cancers]]) – a desire present at every level of human organization that spans across individuals, communities, and society. This reflects a core human desire to be healthy. Yet, recognizing that humanity should strive towards a cure for biological aging is a sentiment that does not attract such widespread popularity.

	Lack of societal support stems from two fundamental misconceptions – that ‘aging’ merely represents the natural chronological passage of time, and that aging is an entirely separate category from ''age-related disease.''<ref>Sierra, F. (2016). The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. ''Cold Spring Harbor perspectives in medicine'', ''6''(4), a025163.</ref> In contrast, the biology of aging research field (biogerontology) ~~understands~~ the mechanisms of aging as the root cause of most of society’s most prevalent, costly, and debilitating diseases.<ref name=":2">[https://www.nature.com/articles/s41586-019-1365-2 Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. ''Nature'', ''571''(7764), 183-192.]</ref><ref name=":14">[[Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. Nature Reviews Drug Discovery, 19(8), 513-532.\|Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]]</ref><ref name=":3">[[Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. Aging cell, 14(4), 497-510.\|Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. ''Aging cell'', ''14''(4), 497-510.]]</ref>		Lack of societal support stems from two fundamental misconceptions – that ‘aging’ merely represents the natural chronological passage of time, and that aging is an entirely separate category from ''age-related disease.''<ref>Sierra, F. (2016). The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span. ''Cold Spring Harbor perspectives in medicine'', ''6''(4), a025163.</ref> In contrast, the biology of aging research field (biogerontology) views the mechanisms of aging as the root cause of most of society’s most prevalent, costly, and debilitating diseases.<ref name=":2">[https://www.nature.com/articles/s41586-019-1365-2 Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019). From discoveries in ageing research to therapeutics for healthy ageing. ''Nature'', ''571''(7764), 183-192.]</ref><ref name=":14">[[Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. Nature Reviews Drug Discovery, 19(8), 513-532.\|Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020). The quest to slow ageing through drug discovery. ''Nature Reviews Drug Discovery'', ''19''(8), 513-532.]]</ref><ref name=":3">[[Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. Aging cell, 14(4), 497-510.\|Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., ... & Fontana, L. (2015). Interventions to slow aging in humans: are we ready?. ''Aging cell'', ''14''(4), 497-510.]]</ref>

	In 2018, for the first time in human history, the number of people aged over 64 became greater than those aged under 5.<ref name=":32" /> This disparity is projected to ~~only~~ widen ~~further~~ with a rapidly aging population.<ref name=":32">Ritchie, H., & Roser, M. (2019). Age structure. ''Our World in Data''.</ref> The clear implications for a substantial increase in age-related disease burden has led to urgent calls from scientists for global society to support aging biology research to increase healthy life expectancy.<ref name=":3" /><ref>[[Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. Science translational medicine, 2(40), 40cm21-40cm21.\|Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. ''Science translational medicine'', ''2''(40), 40cm21-40cm21.]]</ref>		In 2018, for the first time in human history, the number of people aged over 64 became greater than those aged under 5.<ref name=":32" /> This disparity is projected to widen with a rapidly aging population.<ref name=":32">Ritchie, H., & Roser, M. (2019). Age structure. ''Our World in Data''.</ref> The clear implications for a substantial increase in age-related disease burden has led to urgent calls from scientists for global society to support aging biology research to increase healthy life expectancy.<ref name=":3" /><ref>[[Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. Science translational medicine, 2(40), 40cm21-40cm21.\|Rae, M. J., Butler, R. N., Campisi, J., De Grey, A. D., Finch, C. E., Gough, M., ... & Logan, B. J. (2010). The demographic and biomedical case for late-life interventions in aging. ''Science translational medicine'', ''2''(40), 40cm21-40cm21.]]</ref>

	== What is aging? ==		== What is aging? ==

← Older revision		Revision as of 12:25, 21 July 2024
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	Recent experimental breakthroughs have provided early evidence that aspects of aging can be reversed,<ref name=":15">[[Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., ... & Belmonte, J. C. I. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell, 167(7), 1719-1733.\|Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., ... & Belmonte, J. C. I. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. ''Cell'', ''167''(7), 1719-1733.]]</ref><ref name=":16">Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH. Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020 Dec;588(7836):124-9.		Recent experimental breakthroughs have provided early evidence that aspects of aging can be reversed,<ref name=":15">[[Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., ... & Belmonte, J. C. I. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell, 167(7), 1719-1733.\|Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., ... & Belmonte, J. C. I. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. ''Cell'', ''167''(7), 1719-1733.]]</ref><ref name=":16">Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH. Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020 Dec;588(7836):124-9.

	https://www.nature.com/articles/s41586-020-2975-4</ref> ~~further~~ challenging old assumptions ~~about~~ aging simply ~~being~~ a result of ~~chronological~~ time.[[File:ONH regeneration epigenetic reprogramming.png\|center\|frame\|In vivo epigenetic reprogramming can lead to regeneration of the optic nerve in injury and glaucoma mouse models, and lead to visual recovery in natural aging]]		https://www.nature.com/articles/s41586-020-2975-4</ref> challenging old assumptions that aging is simply a result of time passing.[[File:ONH regeneration epigenetic reprogramming.png\|center\|frame\|In vivo epigenetic reprogramming can lead to regeneration of the optic nerve in injury and glaucoma mouse models, and lead to visual recovery in natural aging]]

	[[Epigenetic reprogramming]] is based on work that earnt [https://embryology.med.unsw.edu.au/embryology/index.php/Embryology_History_-_Shinya_Yamanaka Shinya Yamanaka] the 2012 Nobel Prize in Medicine. Yamanaka showed that it was possible to reprogram adult body cells back into biologically immortal pluripotent stem cells that are capable of turning into any cell of the body.<ref name=":17">Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. ''cell'', ''126''(4), 663-676.</ref><ref name=":18">Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. ''cell'', ''131''(5), 861-872.</ref> This was achieved by activating only four transcription factors - the [[Yamanaka factors\|''Yamanaka factors'']] - OCT4, SOX2, KLF4, and MYC (or OSKM).<ref name=":17" /><ref name=":18" />		[[Epigenetic reprogramming]] is based on work that earnt [https://embryology.med.unsw.edu.au/embryology/index.php/Embryology_History_-_Shinya_Yamanaka Shinya Yamanaka] the 2012 Nobel Prize in Medicine. Yamanaka showed that it was possible to reprogram adult body cells back into biologically immortal pluripotent stem cells that are capable of turning into any cell of the body.<ref name=":17">Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. ''cell'', ''126''(4), 663-676.</ref><ref name=":18">Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. ''cell'', ''131''(5), 861-872.</ref> This was achieved by activating only four transcription factors - the [[Yamanaka factors\|''Yamanaka factors'']] - OCT4, SOX2, KLF4, and MYC (or OSKM).<ref name=":17" /><ref name=":18" />