Aging and cancer - Revision history

Dmitry Dzhagarov: /* Peto's paradox */

2023-09-26T10:26:26Z

Peto's paradox

← Older revision		Revision as of 10:26, 26 September 2023
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	=== Peto's paradox ===		=== Peto's paradox ===
	In animals with larger bodies, the larger number of cells might be expected cancer risk would be greater compared to smaller animals. However, this is not the case across species, with various examples of large animals with low or negligible cancer risk.<ref name=":13">Vincze, O., Colchero, F., Lemaître, J. F., Conde, D. A., Pavard, S., Bieuville, M., ... & Giraudeau, M. (2022). Cancer risk across mammals. ''Nature'', ''601''(7892), 263-267.</ref> Peto's paradox arose from the observation that mice live approximately 30 times shorter and have 1000 fewer cells than humans.<ref name=":13" /> ~~Instead, it~~ is thought that differences in various anti-cancer mechanisms account for this paradox.		In animals with larger bodies, the larger number of cells might be expected cancer risk would be greater compared to smaller animals.<ref name="Peto">Perillo, M., Silla, A., Punzo, A., Caliceti, C., Kriete, A., Sell, C., & Lorenzini, A. (2023). Peto’s paradox: nature has used multiple strategies to keep cancer at bay while evolving long lifespans and large body masses. A systematic mini-review. Biomedical Journal, 100654. PMID: 37604250 [https://doi.org/10.1016/j.bj.2023.100654 DOI: 10.1016/j.bj.2023.100654]</ref> However, this is not the case across species, with various examples of large animals with low or negligible cancer risk.<ref name="Peto" /><ref name=":13">Vincze, O., Colchero, F., Lemaître, J. F., Conde, D. A., Pavard, S., Bieuville, M., ... & Giraudeau, M. (2022). Cancer risk across mammals. ''Nature'', ''601''(7892), 263-267.</ref> Peto's paradox arose from the observation that mice live approximately 30 times shorter and have 1000 fewer cells than humans.<ref name=":13" /> It is thought that differences in various anti-cancer mechanisms account for this paradox.<ref name="Peto" />

	== Cancer epidemiology and population aging ==		== Cancer epidemiology and population aging ==

Geroscientist: /* Accelerated aging in cancer survivors */

2023-01-25T10:30:56Z

Accelerated aging in cancer survivors

← Older revision		Revision as of 10:30, 25 January 2023
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	[[File:Age as -1 risk factor for cancer.jpg\|alt=Age as a risk factor for cancer\|thumb\|[https://elifesciences.org/articles/39950 Age as a risk factor for cancer]]]		[[File:Age as -1 risk factor for cancer.jpg\|alt=Age as a risk factor for cancer\|thumb\|[https://elifesciences.org/articles/39950 Age as a risk factor for cancer]]]

	== ~~Accelerated~~ aging ~~in cancer survivors~~ ==		== Cancer survivors experience accelerated aging ==
	~~It is well known that cancer~~ survivors, ~~whether it is~~ children, adults, or the elderly, exhibit accelerated aging.<ref name=":3">Henderson, T. O., Ness, K. K., & Cohen, H. J. (2014). Accelerated aging among cancer survivors: from pediatrics to geriatrics. ''American Society of Clinical Oncology Educational Book'', ''34''(1), e423-e430.</ref> ~~This leads~~ to ~~early onset~~ of ~~age-related diseases~~, such as dementia, heart disease or [[frailty]].		Cancer survivors, including children, adults, or the elderly, exhibit accelerated aging with early onset of age-related diseases.<ref name=":3">Henderson, T. O., Ness, K. K., & Cohen, H. J. (2014). Accelerated aging among cancer survivors: from pediatrics to geriatrics. ''American Society of Clinical Oncology Educational Book'', ''34''(1), e423-e430.</ref>

			By age 45, up to 96% of childhood cancer survivors develop a chronic disease, such as dementia, heart disease or [[frailty]], and about 80% have a disabling or life-threatening condition.<ref>[https://jamanetwork.com/journals/jama/fullarticle/1696100 Hudson, M. M., Ness, K. K., Gurney, J. G., Mulrooney, D. A., Chemaitilly, W., Krull, K. R., ... & Robison, L. L. (2013). Clinical ascertainment of health outcomes among adults treated for childhood cancer. ''Jama'', ''309''(22), 2371-2381.]</ref>

	Childhood cancer survivors are more well-studied than older cancer survivors.<ref name=":3" /> One study found that 8% of survivors were frail by the median age 33, while 22% were pre-frail.<ref name=":4">Ness, K. K., Armstrong, G. T., Kundu, M., Wilson, C. L., Tchkonia, T., & Kirkland, J. L. (2015). Frailty in childhood cancer survivors. ''Cancer'', ''121''(10), 1540-1547.</ref> This is an example of accelerated aging, because these frailty rates are similar to that of older adults.<ref name=":3" /><ref name=":4" />		Childhood cancer survivors are more well-studied than older cancer survivors.<ref name=":3" /> One study found that 8% of survivors were frail by the median age 33, while 22% were pre-frail.<ref name=":4">Ness, K. K., Armstrong, G. T., Kundu, M., Wilson, C. L., Tchkonia, T., & Kirkland, J. L. (2015). Frailty in childhood cancer survivors. ''Cancer'', ''121''(10), 1540-1547.</ref> This is an example of accelerated aging, because these frailty rates are similar to that of older adults.<ref name=":3" /><ref name=":4" />

Andrea at 11:13, 27 December 2022

2022-12-27T11:13:54Z

← Older revision		Revision as of 11:13, 27 December 2022
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	<references />		<references />
	[[Category:Age-related diseases]]		[[Category:Age-related diseases]]
			[[Category:Main list]]

Andrea: category change

2022-12-27T09:33:46Z

category change

← Older revision		Revision as of 09:33, 27 December 2022
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	==== References ====		==== References ====
	<references />		<references />
	~~[[Category:Longevity]]~~
	[[Category:Age-related diseases]]		[[Category:Age-related diseases]]

Andrea: category

2022-12-27T09:31:35Z

Dmitry Dzhagarov: /* Drugs targeting aging as cancer therapeutics */

2022-12-05T10:20:34Z

Drugs targeting aging as cancer therapeutics

← Older revision		Revision as of 10:20, 5 December 2022
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	== Drugs targeting aging as cancer therapeutics ==		== Drugs targeting aging as cancer therapeutics ==

	Drugs that target aging can delay the onset of multiple chronic diseases, or even reverse aspects of organ/tissue aging.<ref name=":7" /> For a drug to meaningfully slow aging, it must also slow the onset of cancer, in tandem with other age-related diseases. As a result, it has been proposed that drugs like rapamycin or senolytics could be used to not only treat or prevent cancer, but also to reduce the burden of chronic disease and frailty that comes following cancer.<ref name=":7" />		Drugs that target aging can delay the onset of multiple chronic diseases, or even reverse aspects of organ/tissue aging.<ref name=":7" /> For a drug to meaningfully slow aging, it must also slow the onset of cancer, in tandem with other age-related diseases. As a result, it has been proposed that drugs like rapamycin or senolytics could be used to not only treat or prevent cancer, but also to reduce the burden of chronic disease and [[frailty]] that comes following cancer.<ref name=":7" />

	=== Rapamycin ===		=== Rapamycin ===

Dmitry Dzhagarov: /* Accelerated aging in cancer survivors */

2022-12-05T10:19:28Z

Accelerated aging in cancer survivors

← Older revision		Revision as of 10:19, 5 December 2022
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	== Accelerated aging in cancer survivors ==		== Accelerated aging in cancer survivors ==
	It is well known that cancer survivors, whether it is children, adults, or the elderly, exhibit accelerated aging.<ref name=":3">Henderson, T. O., Ness, K. K., & Cohen, H. J. (2014). Accelerated aging among cancer survivors: from pediatrics to geriatrics. ''American Society of Clinical Oncology Educational Book'', ''34''(1), e423-e430.</ref> This leads to early onset of age-related diseases, such as dementia, heart disease or frailty.		It is well known that cancer survivors, whether it is children, adults, or the elderly, exhibit accelerated aging.<ref name=":3">Henderson, T. O., Ness, K. K., & Cohen, H. J. (2014). Accelerated aging among cancer survivors: from pediatrics to geriatrics. ''American Society of Clinical Oncology Educational Book'', ''34''(1), e423-e430.</ref> This leads to early onset of age-related diseases, such as dementia, heart disease or [[frailty]].

	Childhood cancer survivors are more well-studied than older cancer survivors.<ref name=":3" /> One study found that 8% of survivors were frail by the median age 33, while 22% were pre-frail.<ref name=":4">Ness, K. K., Armstrong, G. T., Kundu, M., Wilson, C. L., Tchkonia, T., & Kirkland, J. L. (2015). Frailty in childhood cancer survivors. ''Cancer'', ''121''(10), 1540-1547.</ref> This is an example of accelerated aging, because these frailty rates are similar to that of older adults.<ref name=":3" /><ref name=":4" />		Childhood cancer survivors are more well-studied than older cancer survivors.<ref name=":3" /> One study found that 8% of survivors were frail by the median age 33, while 22% were pre-frail.<ref name=":4">Ness, K. K., Armstrong, G. T., Kundu, M., Wilson, C. L., Tchkonia, T., & Kirkland, J. L. (2015). Frailty in childhood cancer survivors. ''Cancer'', ''121''(10), 1540-1547.</ref> This is an example of accelerated aging, because these frailty rates are similar to that of older adults.<ref name=":3" /><ref name=":4" />
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	===== Cellular senescence =====		===== Cellular senescence =====
	A relatively well-studied molecular mechanism associated with accelerated aging in cancer survivors is cellular senescence.<sup><ref name=":0">Smitherman, A. B., Wood, W. A., Mitin, N., Ayer Miller, V. L., Deal, A. M., Davis, I. J., ... & Muss, H. B. (2020). Accelerated aging among childhood, adolescent, and young adult cancer survivors is evidenced by increased expression of p16INK4a and frailty. ''Cancer'', ''126''(22), 4975-4983.</ref></sup> p16<sup>INK4a</sup> expression is a putative marker of cellular senescence and has been shown to be higher among childhood, adolescent, and young adult cancer survivors who are more frail.<sup><ref name=":0" /></sup> There is some evidence that chemotherapy promotes cellular senescence, to increase the accumulation of senescent cells that are associated with aging.		A relatively well-studied molecular mechanism associated with accelerated aging in cancer survivors is cellular senescence.<sup><ref name=":0">Smitherman, A. B., Wood, W. A., Mitin, N., Ayer Miller, V. L., Deal, A. M., Davis, I. J., ... & Muss, H. B. (2020). Accelerated aging among childhood, adolescent, and young adult cancer survivors is evidenced by increased expression of p16INK4a and frailty. ''Cancer'', ''126''(22), 4975-4983.</ref></sup> p16<sup>INK4a</sup> expression is a putative marker of cellular senescence and has been shown to be higher among childhood, adolescent, and young adult cancer survivors who are more frail.<sup><ref name=":0" /></sup> There is some evidence that chemotherapy promotes cellular senescence, to increase the accumulation of senescent cells that are associated with aging.

	== Drugs targeting aging as cancer therapeutics ==		== Drugs targeting aging as cancer therapeutics ==

Andrea: Andrea moved page Aging and Cancer to Aging and cancer: Changed title

2022-08-25T17:20:17Z

Andrea moved page Aging and Cancer to Aging and cancer: Changed title

← Older revision	Revision as of 17:20, 25 August 2022
(No difference)

Geroscientist: /* Rapamycin */

2022-05-19T09:59:48Z

Rapamycin

← Older revision		Revision as of 09:59, 19 May 2022
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	=== Rapamycin ===		=== Rapamycin ===
	For an overview of rapamycin, see this [[Rapamycin\|~~link~~]].		For an overview of rapamycin, see this [[Rapamycin\|article]].

	In a majority of human cancers, there is an increased activity of the mechanistic target of rapamycin (mTOR), which is known to be inhibited by rapamycin.<ref name=":10">Kaeberlein, M. (2013). mTOR inhibition: from aging to autism and beyond. ''Scientifica'', ''2013''.</ref> This has led to human clinical trials studying ~~its~~ potential in various cancers, as monotherapy or as adjuvant.<ref name=":10" />		In a majority of human cancers, there is an increased activity of the mechanistic target of rapamycin (mTOR), which is known to be inhibited by rapamycin.<ref name=":10">Kaeberlein, M. (2013). mTOR inhibition: from aging to autism and beyond. ''Scientifica'', ''2013''.</ref> This has led to human clinical trials studying rapamycin's potential in various cancers, as monotherapy or as adjuvant.<ref name=":10" />

	In the transgenic HER-2/neu mouse model, mice die prematurely due to susceptibility to cancer.<ref name=":62">Anisimov, V. N., Zabezhinski, M. A., Popovich, I. G., Piskunova, T. S., Semenchenko, A. V., Tyndyk, M. L., ... & Blagosklonny, M. V. (2010). Rapamycin extends maximal lifespan in cancer-prone mice. ''The American journal of pathology'', ''176''(5), 2092-2097.</ref> Rapamycin was hypothesized to improve survival in this model due to its ability to slow aging, which would also address an age-related disease like cancer.<ref name=":62" /> The drug was shown to extend maximal lifespan, by delaying aging in multiple different organs and also suppressing cancer development.<ref name=":62" />		In the transgenic HER-2/neu mouse model, mice die prematurely due to susceptibility to cancer.<ref name=":62">Anisimov, V. N., Zabezhinski, M. A., Popovich, I. G., Piskunova, T. S., Semenchenko, A. V., Tyndyk, M. L., ... & Blagosklonny, M. V. (2010). Rapamycin extends maximal lifespan in cancer-prone mice. ''The American journal of pathology'', ''176''(5), 2092-2097.</ref> Rapamycin was hypothesized to improve survival in this model due to its ability to slow aging, which would also address an age-related disease like cancer.<ref name=":62" /> The drug was shown to extend maximal lifespan, by delaying aging in multiple different organs and also suppressing cancer development.<ref name=":62" />

Geroscientist: /* Relevant biological mechanisms */

2022-05-19T09:58:14Z

Relevant biological mechanisms

← Older revision		Revision as of 09:58, 19 May 2022
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	Various biological mechanisms are thought to account for accelerated aging in cancer survivors. These include cellular senescence, mitochondrial dysfunction, and sterile inflammation.<ref name=":4" />		Various biological mechanisms are thought to account for accelerated aging in cancer survivors. These include cellular senescence, mitochondrial dysfunction, and sterile inflammation.<ref name=":4" />
	=== ~~Relevant biological~~ mechanisms ===		=== Biological mechanisms ===

	===== Cellular senescence =====		===== Cellular senescence =====

← Older revision		Revision as of 09:31, 27 December 2022
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	<references />		<references />
	[[Category:Longevity]]		[[Category:Longevity]]
			[[Category:Age-related diseases]]