Hallmarks of aging - Revision history

Dmitry Dzhagarov: /* 10. Cell size */

2024-08-01T17:21:40Z

10. Cell size

← Older revision		Revision as of 17:21, 1 August 2024
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	<ref>Manohar, S., & Neurohr, G. E. (2024). Too big not to fail: emerging evidence for size‐induced senescence. The FEBS Journal, 291(11), 2291-2305. PMID: 37986656 DOI: 10.1111/febs.16983</ref>		<ref>Manohar, S., & Neurohr, G. E. (2024). Too big not to fail: emerging evidence for size‐induced senescence. The FEBS Journal, 291(11), 2291-2305. PMID: 37986656 DOI: 10.1111/febs.16983</ref>
	<ref>Khurana, A., Chadha, Y., & Schmoller, K. M. (2023). Too big not to fail: Different paths lead to senescence of enlarged cells. Molecular Cell, 83(22), 3946-3947. DOI:https://doi.org/10.1016/j.molcel.2023.10.024</ref>		<ref>Khurana, A., Chadha, Y., & Schmoller, K. M. (2023). Too big not to fail: Different paths lead to senescence of enlarged cells. Molecular Cell, 83(22), 3946-3947. DOI:https://doi.org/10.1016/j.molcel.2023.10.024</ref>

			==== [[Small nucleoli as a visible cellular hallmark of longevity and metabolic health\|Correlation between aging and nucleolar size]] ====

	== Critical Review ==		== Critical Review ==

Dmitry Dzhagarov: /* Cell size */

2024-08-01T17:07:09Z

Cell size

← Older revision		Revision as of 17:07, 1 August 2024
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	It's also been found that senescent cells excrete a specific set of molecules called the [[Cellular_senescence#SASP\|'''SASP''']] (Senescence-Associated Secretory Phenotype) which induce [[Cellular senescence\|senescence]] in neighboring cells. Conversely, lifespan-extending manipulations targeting one tissue can slow the aging process in other tissues as well.		It's also been found that senescent cells excrete a specific set of molecules called the [[Cellular_senescence#SASP\|'''SASP''']] (Senescence-Associated Secretory Phenotype) which induce [[Cellular senescence\|senescence]] in neighboring cells. Conversely, lifespan-extending manipulations targeting one tissue can slow the aging process in other tissues as well.

	=== Cell size ===		=== 10. Cell size ===
	<ref>Lengefeld, J., Cheng, C. W., Maretich, P., Blair, M., Hagen, H., McReynolds, M. R., ... & Amon, A. (2021). Cell size is a determinant of stem cell potential during aging. Science advances, 7(46), eabk0271.</ref>		<ref>Lengefeld, J., Cheng, C. W., Maretich, P., Blair, M., Hagen, H., McReynolds, M. R., ... & Amon, A. (2021). Cell size is a determinant of stem cell potential during aging. Science advances, 7(46), eabk0271.</ref>
	<ref>Biran, A., Zada, L., Abou Karam, P., Vadai, E., Roitman, L., Ovadya, Y., ... & Krizhanovsky, V. (2017). Quantitative identification of senescent cells in aging and disease. Aging cell, 16(4), 661-671. PMID: 28455874 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506427/ PMC5506427] DOI: 10.1111/acel.12592</ref>		<ref>Biran, A., Zada, L., Abou Karam, P., Vadai, E., Roitman, L., Ovadya, Y., ... & Krizhanovsky, V. (2017). Quantitative identification of senescent cells in aging and disease. Aging cell, 16(4), 661-671. PMID: 28455874 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506427/ PMC5506427] DOI: 10.1111/acel.12592</ref>
	<ref>Vidal, P. J., Pérez, A. P., Yahya, G., & Aldea, M. (2024). Transcriptomic balance and optimal growth are determined by cell size. Molecular Cell. https://doi.org/10.1016/j.molcel.2024.07.005</ref>		<ref>Vidal, P. J., Pérez, A. P., Yahya, G., & Aldea, M. (2024). Transcriptomic balance and optimal growth are determined by cell size. Molecular Cell. https://doi.org/10.1016/j.molcel.2024.07.005</ref>
	<ref>Pérez-Ortín, J. E., García-Marcelo, M. J., Delgado-Román, I., Muñoz-Centeno, M. C., & Chávez, S. (2024). Influence of cell volume on the gene transcription rate. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 195008. PMID: 38246270 DOI: 10.1016/j.bbagrm.2024.195008</ref>		<ref>Pérez-Ortín, J. E., García-Marcelo, M. J., Delgado-Román, I., Muñoz-Centeno, M. C., & Chávez, S. (2024). Influence of cell volume on the gene transcription rate. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 195008. PMID: 38246270 DOI: 10.1016/j.bbagrm.2024.195008</ref>
			<ref>Lanz, M. C., Zatulovskiy, E., Swaffer, M. P., Zhang, L., Ilerten, I., Zhang, S., ... & Skotheim, J. M. (2022). Increasing cell size remodels the proteome and promotes senescence. Molecular cell, 82(17), 3255-3269. PMID: 35987199 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444988/ PMC9444988] DOI: 10.1016/j.molcel.2022.07.017</ref>
			<ref>Manohar, S., & Neurohr, G. E. (2024). Too big not to fail: emerging evidence for size‐induced senescence. The FEBS Journal, 291(11), 2291-2305. PMID: 37986656 DOI: 10.1111/febs.16983</ref>
			<ref>Khurana, A., Chadha, Y., & Schmoller, K. M. (2023). Too big not to fail: Different paths lead to senescence of enlarged cells. Molecular Cell, 83(22), 3946-3947. DOI:https://doi.org/10.1016/j.molcel.2023.10.024</ref>

	== Critical Review ==		== Critical Review ==

Dmitry Dzhagarov: /* 9. Altered intercellular communication */

2024-08-01T16:20:26Z

9. Altered intercellular communication

← Older revision		Revision as of 16:20, 1 August 2024
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	It's also been found that senescent cells excrete a specific set of molecules called the [[Cellular_senescence#SASP\|'''SASP''']] (Senescence-Associated Secretory Phenotype) which induce [[Cellular senescence\|senescence]] in neighboring cells. Conversely, lifespan-extending manipulations targeting one tissue can slow the aging process in other tissues as well.		It's also been found that senescent cells excrete a specific set of molecules called the [[Cellular_senescence#SASP\|'''SASP''']] (Senescence-Associated Secretory Phenotype) which induce [[Cellular senescence\|senescence]] in neighboring cells. Conversely, lifespan-extending manipulations targeting one tissue can slow the aging process in other tissues as well.

			=== Cell size ===
			<ref>Lengefeld, J., Cheng, C. W., Maretich, P., Blair, M., Hagen, H., McReynolds, M. R., ... & Amon, A. (2021). Cell size is a determinant of stem cell potential during aging. Science advances, 7(46), eabk0271.</ref>
			<ref>Biran, A., Zada, L., Abou Karam, P., Vadai, E., Roitman, L., Ovadya, Y., ... & Krizhanovsky, V. (2017). Quantitative identification of senescent cells in aging and disease. Aging cell, 16(4), 661-671. PMID: 28455874 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506427/ PMC5506427] DOI: 10.1111/acel.12592</ref>
			<ref>Vidal, P. J., Pérez, A. P., Yahya, G., & Aldea, M. (2024). Transcriptomic balance and optimal growth are determined by cell size. Molecular Cell. https://doi.org/10.1016/j.molcel.2024.07.005</ref>
			<ref>Pérez-Ortín, J. E., García-Marcelo, M. J., Delgado-Román, I., Muñoz-Centeno, M. C., & Chávez, S. (2024). Influence of cell volume on the gene transcription rate. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 195008. PMID: 38246270 DOI: 10.1016/j.bbagrm.2024.195008</ref>

	== Critical Review ==		== Critical Review ==

Dmitry Dzhagarov: /* 5. Deregulated nutrient-sensing */

2024-06-19T16:26:53Z

5. Deregulated nutrient-sensing

← Older revision		Revision as of 16:26, 19 June 2024
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	''See the full article on [[metabolic flexibility]].''		''See the full article on [[metabolic flexibility]].''

	Nutrient sensing is a cell's ability to recognize, and respond to, changes in the concentration of macronutrients such as glucose, fatty acids and amino acids. In times of abundance, anabolism is induced through various pathways, the most well-studied among them the mTOR pathway. When energy and nutrients are scarce, proteins such as the AMPK receptor senses this and turns down mTOR to conserve resources.		Nutrient sensing is a cell's ability to recognize, and respond to, changes in the concentration of macronutrients such as glucose, fatty acids and amino acids. In times of abundance, anabolism is induced through various pathways, the most well-studied among them the [[mTOR]] pathway. When energy and nutrients are scarce, proteins such as the AMPK receptor senses this and turns down mTOR to conserve resources.

	In a growing organism, growth and cell proliferation are important and thus mTOR is upregulated. In a fully grown organism, mTOR-activating signals naturally decline during aging. It has been found that forcibly overactivating these pathways in grown mice leads to accelerated aging and increased incidence of cancer. mTOR inhibition methods like [[Calorie restriction\|dietary restriction]] or [[rapamycin]] have been shown to be one of the most robust methods of increasing healthy lifespan in worms, flies and mice.		In a growing organism, growth and cell proliferation are important and thus mTOR is upregulated. In a fully grown organism, mTOR-activating signals naturally decline during aging. It has been found that forcibly overactivating these pathways in grown mice leads to accelerated aging and increased incidence of cancer. mTOR inhibition methods like [[Calorie restriction\|dietary restriction]] or [[rapamycin]] have been shown to be one of the most robust methods of increasing healthy lifespan in worms, flies and mice.

Dmitry Dzhagarov: /* References */

2024-03-20T16:40:34Z

References

← Older revision		Revision as of 16:40, 20 March 2024
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	[[Category:Aging pathways and hallmarks]]		[[Category:Aging pathways and hallmarks]]
	[[Category:Fundamentals]]		[[Category:Fundamentals]]
			[[Category:Database]]

Dmitry Dzhagarov: /* Critical Review */

2024-03-20T16:36:38Z

Critical Review

← Older revision		Revision as of 16:36, 20 March 2024
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	Consequently, these hallmarks do not offer a ''causal'' explanation as to ''why'' we age, and could potentially just offer a phenotypic observation of associated aging features. In other words, these observed hallmarks might be a result of an upstream unknown aging process, similar to how the appearance of wrinkles or white hairs is known to be associated to older individuals.		Consequently, these hallmarks do not offer a ''causal'' explanation as to ''why'' we age, and could potentially just offer a phenotypic observation of associated aging features. In other words, these observed hallmarks might be a result of an upstream unknown aging process, similar to how the appearance of wrinkles or white hairs is known to be associated to older individuals.

	Another important aspect of the Hallmarks of Aging by López-Otín et al., is the limitation of its scope to a whole-organism level. The latest high-throughout RNA-seq studies, including from the longevity-research giant [https://www.calicolabs.com Calico], have demonstrated that aging is largely regulated in a tissue-specific manner and that age-dependent changes vary enormously according to cell type.<ref name=":4">Roux, A., Yuan, H., Podshivalova, K., Hendrickson, D., Kerr, R., Kenyon, C., & Kelley, D. (2022). The complete cell atlas of an aging multicellular organism. doi: 10.1101/2022.06.15.496201</ref><ref>Wang, X., Jiang, Q., Song, Y., He, Z., Zhang, H., & Song, M. et al. (2022). Ageing induces tissue‐specific transcriptomic changes in ''Caenorhabditis elegans''. ''The EMBO Journal'', ''41''(8). doi: 10.15252/embj.2021109633</ref> In fact, down-regulation of energy metabolism pathways during aging is the only universal change observed across all cell types.<ref name=":4" /> This highlights the importance of building a more comprehensive tissue-specific reference for the hallmarks of aging, as it has already been explored in the context of [[Aging and Neurodegeneration\|neurodegenerative diseases.]]<ref>Mattson, M., & Arumugam, T. (2018). Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States. ''Cell Metabolism'', ''27''(6), 1176-1199. doi: 10.1016/j.cmet.2018.05.011</ref>		Another important aspect of the Hallmarks of Aging by López-Otín et al., is the limitation of its scope to a whole-organism level. The latest high-throughout RNA-seq studies, including from the longevity-research giant [https://www.calicolabs.com Calico], have demonstrated that aging is largely regulated in a tissue-specific manner and that age-dependent changes vary enormously according to cell type.<ref name=":4">Roux, A., Yuan, H., Podshivalova, K., Hendrickson, D., Kerr, R., Kenyon, C., & Kelley, D. (2022). The complete cell atlas of an aging multicellular organism. doi: 10.1101/2022.06.15.496201</ref><ref>Wang, X., Jiang, Q., Song, Y., He, Z., Zhang, H., & Song, M. et al. (2022). Ageing induces tissue‐specific transcriptomic changes in ''Caenorhabditis elegans''. ''The EMBO Journal'', ''41''(8). doi: 10.15252/embj.2021109633</ref> In fact, down-regulation of energy metabolism pathways during aging is the only universal change observed across all cell types.<ref name=":4" /> This highlights the importance of building a more comprehensive tissue-specific reference, for the hallmarks of aging, as it has already been explored in the context of [[Aging and Neurodegeneration\|neurodegenerative diseases.]]<ref>Mattson, M., & Arumugam, T. (2018). Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States. ''Cell Metabolism'', ''27''(6), 1176-1199. doi: 10.1016/j.cmet.2018.05.011</ref>

			'''PanSci''', a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissue samples, encompassing a range of organs across different life stages, sexes, and genotypes allowed to identify more than 3,000 unique cellular states and catalog over 200 distinct aging-associated cell populations experiencing significant depletion or expansion. Panoramic analysis uncovered temporally structured, organ- and lineage-specific shifts of cellular dynamics during lifespan progression. Including aging-associated alterations in immune cell populations, revealing both widespread shifts and organ-specific changes.<ref>Zhang, Z., Schaefer, C., Jiang, W., Lu, Z., Lee, J., Sziraki, A., ... & Cao, J. (2024). A Panoramic View of Cell Population Dynamics in Mammalian Aging. bioRxiv, 2024-03. https://doi.org/10.1101/2024.03.01.583001</ref>

	Nonetheless, and similarly to the case of [[Epigenetic clock\|epigenetic clocks]], the Hallmarks of Aging might provide a useful framework to examine the effect of rejuvenating interventions, until more exhaustive studies of the hallmarks of aging are available at the tissue level.		Nonetheless, and similarly to the case of [[Epigenetic clock\|epigenetic clocks]], the Hallmarks of Aging might provide a useful framework to examine the effect of rejuvenating interventions, until more exhaustive studies of the hallmarks of aging are available at the tissue level.

Dmitry Dzhagarov: /* Biomarkers of aging */

2023-12-28T20:01:07Z

Biomarkers of aging

← Older revision		Revision as of 20:01, 28 December 2023
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	=== Biomarkers of aging ===		=== Biomarkers of aging ===
	<ref>Aging Biomarker Consortium., Bao, H., Cao, J. et al. (2023). Biomarkers of aging. Sci. China Life Sci. https://doi.org/10.1007/s11427-023-2305-0</ref>		<ref>Aging Biomarker Consortium., Bao, H., Cao, J. et al. (2023). [https://www.researchgate.net/profile/Ruici-Yang/publication/370003516_Biomarkers_of_aging/links/6438fa43168a0b54ecca954a/Biomarkers-of-aging.pdf Biomarkers of aging.] Sci. China Life Sci. https://doi.org/10.1007/s11427-023-2305-0</ref>

	== References ==		== References ==

Andrea: /* added hyperlink */

2023-07-20T19:09:29Z

added hyperlink

← Older revision		Revision as of 19:09, 20 July 2023
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	=== 1. Genomic instability ===		=== 1. Genomic instability ===
			''See the full article on [[DNA damage and repair]]''

	The genome is the total sum of DNA in our body and becomes damaged over time, with genomic instability leading to various age-related health problems.<ref name=":0" /> DNA carries the information to make proteins that make up cells and tissues in living organisms.		The genome is the total sum of DNA in our body and becomes damaged over time, with genomic instability leading to various age-related health problems.<ref name=":0" /> DNA carries the information to make proteins that make up cells and tissues in living organisms.

Dmitry Dzhagarov: /* 9. Altered intercellular communication */

2023-05-13T15:57:27Z

9. Altered intercellular communication

← Older revision		Revision as of 15:57, 13 May 2023
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	One of the most prominent changes in cell signaling biomarkers is "[[inflammaging]]", the development of a chronic low-grade inflammation throughout the body with advanced age. The normal role of inflammation is to recruit the body's immune system and repair mechanisms to a specific damaged area for as long as the damage and threat are present. The constant presence of inflammation markers throughout the body wears out the immune system and damages healthy tissue.		One of the most prominent changes in cell signaling biomarkers is "[[inflammaging]]", the development of a chronic low-grade inflammation throughout the body with advanced age. The normal role of inflammation is to recruit the body's immune system and repair mechanisms to a specific damaged area for as long as the damage and threat are present. The constant presence of inflammation markers throughout the body wears out the immune system and damages healthy tissue.

	It's also been found that senescent cells excrete a specific set of molecules called the SASP (Senescence-Associated Secretory Phenotype) which induce [[Cellular senescence\|senescence]] in neighboring cells. Conversely, lifespan-extending manipulations targeting one tissue can slow the aging process in other tissues as well.		It's also been found that senescent cells excrete a specific set of molecules called the [[Cellular_senescence#SASP\|'''SASP''']] (Senescence-Associated Secretory Phenotype) which induce [[Cellular senescence\|senescence]] in neighboring cells. Conversely, lifespan-extending manipulations targeting one tissue can slow the aging process in other tissues as well.

	== Critical Review ==		== Critical Review ==

Dmitry Dzhagarov: /* Critical Review */

2023-05-03T14:45:06Z

Critical Review

← Older revision		Revision as of 14:45, 3 May 2023
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	Nonetheless, and similarly to the case of [[Epigenetic clock\|epigenetic clocks]], the Hallmarks of Aging might provide a useful framework to examine the effect of rejuvenating interventions, until more exhaustive studies of the hallmarks of aging are available at the tissue level.		Nonetheless, and similarly to the case of [[Epigenetic clock\|epigenetic clocks]], the Hallmarks of Aging might provide a useful framework to examine the effect of rejuvenating interventions, until more exhaustive studies of the hallmarks of aging are available at the tissue level.

			=== Biomarkers of aging ===
			<ref>Aging Biomarker Consortium., Bao, H., Cao, J. et al. (2023). Biomarkers of aging. Sci. China Life Sci. https://doi.org/10.1007/s11427-023-2305-0</ref>

	== References ==		== References ==