Mitochondrial dysfunction - Revision history

Dmitry Dzhagarov at 20:04, 30 May 2024

2024-05-30T20:04:47Z

← Older revision		Revision as of 20:04, 30 May 2024
Line 1:		Line 1:
	Mitochondrial dysfunction is a state of inefficient energy production resulting from damage to energy-producing structures called mitochondria.<ref name=":17">Cui, H., Kong, Y., & Zhang, H. (2012). Oxidative stress, mitochondrial dysfunction, and aging. ''Journal of signal transduction'', ''2012''.</ref><ref>Liu, S. Z., Chiao, Y. A., Rabinovitch, P. S., & Marcinek, D. J. (2024). Mitochondrial Targeted Interventions for Aging. Cold Spring Harbor Perspectives in Medicine, 14(3), a041199. PMID: 37788882 PMC10910403 (available on 2026-03-01) [http://perspectivesinmedicine.cshlp.org/content/14/3/a041199.abstract DOI: 10.1101/cshperspect.a041199]</ref>		Mitochondrial dysfunction is a state of inefficient energy production resulting from damage to energy-producing structures called mitochondria.<ref name=":17">Cui, H., Kong, Y., & Zhang, H. (2012). Oxidative stress, mitochondrial dysfunction, and aging. ''Journal of signal transduction'', ''2012''.</ref><ref>Liu, S. Z., Chiao, Y. A., Rabinovitch, P. S., & Marcinek, D. J. (2024). Mitochondrial Targeted Interventions for Aging. Cold Spring Harbor Perspectives in Medicine, 14(3), a041199. PMID: 37788882 PMC10910403 (available on 2026-03-01) [http://perspectivesinmedicine.cshlp.org/content/14/3/a041199.abstract DOI: 10.1101/cshperspect.a041199]</ref><ref>Suomalainen, A., & Nunnari, J. (2024). Mitochondria at the crossroads of health and disease. Cell, 187(11), 2601-2627. PMID: 38788685 [https://doi.org/10.1016/j.cell.2024.04.037 DOI: 10.1016/j.cell.2024.04.037]</ref>

	== Introduction ==		== Introduction ==

Dmitry Dzhagarov at 13:35, 20 March 2024

2024-03-20T13:35:34Z

← Older revision		Revision as of 13:35, 20 March 2024
Line 1:		Line 1:
	Mitochondrial dysfunction is a state of inefficient energy production resulting from damage to energy-producing structures called mitochondria.<ref name=":17">Cui, H., Kong, Y., & Zhang, H. (2012). Oxidative stress, mitochondrial dysfunction, and aging. ''Journal of signal transduction'', ''2012''.</ref>		Mitochondrial dysfunction is a state of inefficient energy production resulting from damage to energy-producing structures called mitochondria.<ref name=":17">Cui, H., Kong, Y., & Zhang, H. (2012). Oxidative stress, mitochondrial dysfunction, and aging. ''Journal of signal transduction'', ''2012''.</ref><ref>Liu, S. Z., Chiao, Y. A., Rabinovitch, P. S., & Marcinek, D. J. (2024). Mitochondrial Targeted Interventions for Aging. Cold Spring Harbor Perspectives in Medicine, 14(3), a041199. PMID: 37788882 PMC10910403 (available on 2026-03-01) [http://perspectivesinmedicine.cshlp.org/content/14/3/a041199.abstract DOI: 10.1101/cshperspect.a041199]</ref>

	== Introduction ==		== Introduction ==

Andrea: category change and hyperlinks

2022-12-27T12:54:19Z

category change and hyperlinks

← Older revision		Revision as of 12:54, 27 December 2022
Line 1:		Line 1:
	~~<gallery widths="1000">~~		Mitochondrial dysfunction is a state of inefficient energy production resulting from damage to energy-producing structures called mitochondria.<ref name=":17">Cui, H., Kong, Y., & Zhang, H. (2012). Oxidative stress, mitochondrial dysfunction, and aging. ''Journal of signal transduction'', ''2012''.</ref>
	~~</gallery>~~Mitochondrial dysfunction is a state of inefficient energy production resulting from damage to energy-producing structures called mitochondria.<ref name=":17">Cui, H., Kong, Y., & Zhang, H. (2012). Oxidative stress, mitochondrial dysfunction, and aging. ''Journal of signal transduction'', ''2012''.</ref>

	== Introduction ==		== Introduction ==
Line 8:		Line 7:
	</ref>		</ref>

	Mitochondrial dysfunction, and especially dysfunction of mitochondrial dynamics, is considered a hallmark of aging and has been implicated in age-related diseases such as osteoporosis or [[Aging and Neurodegeneration\|Alzheimer’s and Parkinson’s disease]]<ref name=":2">Age-related mitochondrial dysfunction as a key factor in COVID-19 disease. (2020). ''Experimental Gerontology, 142'', 111147. <nowiki>https://doi.org/10.1016/j.exger.2020.111147</nowiki></ref><ref name=":3">Chen, C., Turnbull, D. M., & Reeve, A. K. (2019). Mitochondrial dysfunction in Parkinson’s disease—Cause or consequence? ''Biology, 8''(2). <nowiki>https://doi.org/10.3390/biology8020038</nowiki></ref><ref name=":4">López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. ''Cell, 153''(6), 1194–1217. <nowiki>https://doi.org/10.1016/j.cell.2013.05.039</nowiki></ref><ref name=":20">Weir, H., Yao, P., Huynh, F., Escoubas, C., Goncalves, R., & Burkewitz, K. et al. (2017). Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling. ''Cell Metabolism'', ''26''(6), 884-896.e5. doi: 10.1016/j.cmet.2017.09.024</ref>. [[Mitochondria]] are highly dynamic organelles that undergo coordinated cycles of fission and fusion in order to maintain their shape, distribution and size, as shown by imaging studies in live cells<ref>Okamoto, K., & Shaw, J. (2005). Mitochondrial Morphology and Dynamics in Yeast and Multicellular Eukaryotes. ''Annual Review Of Genetics'', ''39''(1), 503-536. doi: 10.1146/annurev.genet.38.072902.093019</ref>. These dynamical processes are key for regulating organismal homeostasis and are required to maintain appropriate [[metabolic flexibility]]<ref>Tilokani, L., Nagashima, S., Paupe, V., & Prudent, J. (2018). Mitochondrial dynamics: overview of molecular mechanisms. ''Essays In Biochemistry'', ''62''(3), 341-360. doi: 10.1042/ebc20170104</ref>.		Mitochondrial dysfunction, and especially dysfunction of mitochondrial dynamics, is considered a [[Hallmarks of aging\|hallmark of aging]] and has been implicated in age-related diseases such as osteoporosis or [[Aging and Neurodegeneration\|Alzheimer’s and Parkinson’s disease]]<ref name=":2">Age-related mitochondrial dysfunction as a key factor in COVID-19 disease. (2020). ''Experimental Gerontology, 142'', 111147. <nowiki>https://doi.org/10.1016/j.exger.2020.111147</nowiki></ref><ref name=":3">Chen, C., Turnbull, D. M., & Reeve, A. K. (2019). Mitochondrial dysfunction in Parkinson’s disease—Cause or consequence? ''Biology, 8''(2). <nowiki>https://doi.org/10.3390/biology8020038</nowiki></ref><ref name=":4">López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. ''Cell, 153''(6), 1194–1217. <nowiki>https://doi.org/10.1016/j.cell.2013.05.039</nowiki></ref><ref name=":20">Weir, H., Yao, P., Huynh, F., Escoubas, C., Goncalves, R., & Burkewitz, K. et al. (2017). Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling. ''Cell Metabolism'', ''26''(6), 884-896.e5. doi: 10.1016/j.cmet.2017.09.024</ref>. [[Mitochondria]] are highly dynamic organelles that undergo coordinated cycles of fission and fusion in order to maintain their shape, distribution and size, as shown by imaging studies in live cells<ref>Okamoto, K., & Shaw, J. (2005). Mitochondrial Morphology and Dynamics in Yeast and Multicellular Eukaryotes. ''Annual Review Of Genetics'', ''39''(1), 503-536. doi: 10.1146/annurev.genet.38.072902.093019</ref>. These dynamical processes are key for regulating organismal homeostasis and are required to maintain appropriate [[metabolic flexibility]]<ref>Tilokani, L., Nagashima, S., Paupe, V., & Prudent, J. (2018). Mitochondrial dynamics: overview of molecular mechanisms. ''Essays In Biochemistry'', ''62''(3), 341-360. doi: 10.1042/ebc20170104</ref>.

	== Basics of mitochondria ==		== Basics of mitochondria ==
Line 28:		Line 27:

	== Inflammation ==		== Inflammation ==
	Mitochondrial dysfunction can contribute to a chronic background level of inflammation some call "inflammaging".<ref name=":1" /> As the name suggests, this problem occurs with aging. Inflammaging has been associated with increased morbidity and mortality, but some researchers have found high levels of pro-inflammatory markers in people over 100 years old. This casts some doubt on whether inflammaging truly harms the elderly.<ref name=":7" /> Mitochondrial dysfunction contributes to inflammaging by increasing the cell's ROS levels.<ref name=":1" /> Increased ROS modulate the expression and activity of a substance called NF-κB, which leads to inflammation.<ref name=":7" /> Mitochondrial dysfunction may also contribute to inflammaging through mtDNA; that is, it may cause mitochondria to release mtDNA, which causes an inflammatory response when the immune system mistakes the mtDNA for pathogens.<ref name=":11">Dobson, P. F., Dennis, E. P., Hipps, D., Reeve, A., Laude, A., Bradshaw, C., Stamp, C., Smith, A., Deehan, D. J., Turnbull, D. M., & Greaves, L. C. (2020). Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss. ''Scientific Reports, 10.'' <nowiki>https://doi.org/10.1038/s41598-020-68566-2</nowiki></ref><ref name=":7" /> Scientists believe this occurs due to mitochondria's bacterial origins.<ref name=":7" />		Mitochondrial dysfunction can contribute to a chronic background level of inflammation some call "[[inflammaging]]".<ref name=":1" /> As the name suggests, this problem occurs with aging. Inflammaging has been associated with increased morbidity and mortality, but some researchers have found high levels of pro-inflammatory markers in people over 100 years old. This casts some doubt on whether inflammaging truly harms the elderly.<ref name=":7" /> Mitochondrial dysfunction contributes to inflammaging by increasing the cell's ROS levels.<ref name=":1" /> Increased ROS modulate the expression and activity of a substance called NF-κB, which leads to inflammation.<ref name=":7" /> Mitochondrial dysfunction may also contribute to inflammaging through mtDNA; that is, it may cause mitochondria to release mtDNA, which causes an inflammatory response when the immune system mistakes the mtDNA for pathogens.<ref name=":11">Dobson, P. F., Dennis, E. P., Hipps, D., Reeve, A., Laude, A., Bradshaw, C., Stamp, C., Smith, A., Deehan, D. J., Turnbull, D. M., & Greaves, L. C. (2020). Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss. ''Scientific Reports, 10.'' <nowiki>https://doi.org/10.1038/s41598-020-68566-2</nowiki></ref><ref name=":7" /> Scientists believe this occurs due to mitochondria's bacterial origins.<ref name=":7" />

	== Mitochondrial dynamics in aging ==		== Mitochondrial dynamics in aging ==
Line 71:		Line 70:
	== Citations ==		== Citations ==
	<references />		<references />
	[[Category:~~Longevity~~]]		[[Category:Main list]]
			[[Category:Aging pathways and hallmarks]]

Andrea: /* name change Mitochondrial dysfunction in disease */

2022-11-29T20:44:19Z

name change Mitochondrial dysfunction in disease

← Older revision		Revision as of 20:44, 29 November 2022
Line 37:		Line 37:
	Surprisingly, adynamic mitochondria, which show no deterioration of the mitochondrial network, doubles maximum lifespan in worms.<ref name=":20" /> However, worms with adynamic mitochondria are no longer able to respond to metabolic stresses and therefore do not have additional lifespan extension from AMPK activation or calorie restriction interventions.		Surprisingly, adynamic mitochondria, which show no deterioration of the mitochondrial network, doubles maximum lifespan in worms.<ref name=":20" /> However, worms with adynamic mitochondria are no longer able to respond to metabolic stresses and therefore do not have additional lifespan extension from AMPK activation or calorie restriction interventions.

	== Mitochondrial dysfunction in ~~disease~~ ==		== Mitochondrial dysfunction in age-related diseases ==
	''See the full article on [[Aging and Neurodegeneration\|aging and neurodegeneration]].''		''See the full article on [[Aging and Neurodegeneration\|aging and neurodegeneration]].''

Andrea: /* changed name of Mitochondrial dynamics */

2022-11-29T20:43:34Z

changed name of Mitochondrial dynamics

← Older revision		Revision as of 20:43, 29 November 2022
Line 30:		Line 30:
	Mitochondrial dysfunction can contribute to a chronic background level of inflammation some call "inflammaging".<ref name=":1" /> As the name suggests, this problem occurs with aging. Inflammaging has been associated with increased morbidity and mortality, but some researchers have found high levels of pro-inflammatory markers in people over 100 years old. This casts some doubt on whether inflammaging truly harms the elderly.<ref name=":7" /> Mitochondrial dysfunction contributes to inflammaging by increasing the cell's ROS levels.<ref name=":1" /> Increased ROS modulate the expression and activity of a substance called NF-κB, which leads to inflammation.<ref name=":7" /> Mitochondrial dysfunction may also contribute to inflammaging through mtDNA; that is, it may cause mitochondria to release mtDNA, which causes an inflammatory response when the immune system mistakes the mtDNA for pathogens.<ref name=":11">Dobson, P. F., Dennis, E. P., Hipps, D., Reeve, A., Laude, A., Bradshaw, C., Stamp, C., Smith, A., Deehan, D. J., Turnbull, D. M., & Greaves, L. C. (2020). Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss. ''Scientific Reports, 10.'' <nowiki>https://doi.org/10.1038/s41598-020-68566-2</nowiki></ref><ref name=":7" /> Scientists believe this occurs due to mitochondria's bacterial origins.<ref name=":7" />		Mitochondrial dysfunction can contribute to a chronic background level of inflammation some call "inflammaging".<ref name=":1" /> As the name suggests, this problem occurs with aging. Inflammaging has been associated with increased morbidity and mortality, but some researchers have found high levels of pro-inflammatory markers in people over 100 years old. This casts some doubt on whether inflammaging truly harms the elderly.<ref name=":7" /> Mitochondrial dysfunction contributes to inflammaging by increasing the cell's ROS levels.<ref name=":1" /> Increased ROS modulate the expression and activity of a substance called NF-κB, which leads to inflammation.<ref name=":7" /> Mitochondrial dysfunction may also contribute to inflammaging through mtDNA; that is, it may cause mitochondria to release mtDNA, which causes an inflammatory response when the immune system mistakes the mtDNA for pathogens.<ref name=":11">Dobson, P. F., Dennis, E. P., Hipps, D., Reeve, A., Laude, A., Bradshaw, C., Stamp, C., Smith, A., Deehan, D. J., Turnbull, D. M., & Greaves, L. C. (2020). Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss. ''Scientific Reports, 10.'' <nowiki>https://doi.org/10.1038/s41598-020-68566-2</nowiki></ref><ref name=":7" /> Scientists believe this occurs due to mitochondria's bacterial origins.<ref name=":7" />

	== Mitochondrial dynamics ==		== Mitochondrial dynamics in aging ==
	''See the full article on [[metabolic flexibility]].''		''See the full article on [[metabolic flexibility]].''

Andrea: Andrea moved page Mitochondrial Dysfunction to Mitochondrial dysfunction: Changed title

2022-08-25T17:21:34Z

Andrea moved page Mitochondrial Dysfunction to Mitochondrial dysfunction: Changed title

← Older revision	Revision as of 17:21, 25 August 2022
(No difference)

Andrea: /* COVID-19 */

2022-08-12T14:06:26Z

COVID-19

← Older revision		Revision as of 14:06, 12 August 2022
Line 59:		Line 59:

	=== COVID-19 ===		=== COVID-19 ===
			''See the full article on [[COVID-19]].''

	Note: Information below describes the relationship between COVID-19 and mitochondrial dysfunction. For details on the relationship between COVID-19 and the aging process in general, see [[COVID-19]].		Note: Information below describes the relationship between COVID-19 and mitochondrial dysfunction. For details on the relationship between COVID-19 and the aging process in general, see [[COVID-19]].

Andrea: /* Mitochondrial dynamics */

2022-08-12T14:02:57Z

Mitochondrial dynamics

← Older revision		Revision as of 14:02, 12 August 2022
Line 31:		Line 31:

	== Mitochondrial dynamics ==		== Mitochondrial dynamics ==
	During aging, mitochondria acquire a less structured morphology and there is a progressive loss of network connectivity as well as mitochondria content.<ref name=":20" /> ~~Work from the Mair lab showed that~~ [[Calorie restriction\|~~dietary~~ restriction]] and constitutive activation of AMPK in C. ''elegans'' leads to a more youthful mitochondrial morphology~~. The resulting~~ lifespan ~~increase~~ in ~~these~~ worms ~~was shown to require~~ mitochondrial ~~fusion~~ in ~~peripheral tissues~~.<ref name=":20" /> ~~Importantly~~, ~~they showed that enhancing fusion itself is not~~ able to ~~increase lifespan, but that maintaining mitochondrial network homeostasis is sufficient for lifespan extension. By blocking certain components of the mitochondrial machinery and subjecting worms~~ to ~~different dietary interventions~~ and then measuring their lifespans, they showed that the requirement for mitochondrial dynamics appears to be highly context-specific. For instance, intermittent fasting (IF) requires functional mitochondrial dynamics for its associated lifespan extension ~~phenotype. However, chronic dietary~~ restriction ~~without IF still leads to lifespan extension regardless of impaired mitochondrial dynamics~~.~~<ref name=":20" />~~		''See the full article on [[metabolic flexibility]].''

			During aging, mitochondria acquire a less structured morphology and there is a progressive loss of network connectivity as well as mitochondria content.<ref name=":20" /> [[Calorie restriction\|Dietary restriction]] and constitutive activation of AMPK in C. ''elegans'' leads to a more youthful mitochondrial morphology and extends lifespan in worms.

			Surprisingly, adynamic mitochondria, which show no deterioration of the mitochondrial network, doubles maximum lifespan in worms.<ref name=":20" /> However, worms with adynamic mitochondria are no longer able to respond to metabolic stresses and therefore do not have additional lifespan extension from AMPK activation or calorie restriction interventions.

	== Mitochondrial dysfunction in disease ==		== Mitochondrial dysfunction in disease ==
	Mitochondrial dysfunction contributes to a number of aging-related ailments.		''See the full article on [[Aging and Neurodegeneration\|aging and neurodegeneration]].''

			Mitochondrial dysfunction contributes to a number of aging-related ailments:

	=== Alzheimer's disease ===		=== Alzheimer's disease ===

Andrea at 20:58, 19 June 2022

2022-06-19T20:58:05Z

← Older revision		Revision as of 20:58, 19 June 2022
Line 8:		Line 8:
	</ref>		</ref>

	Mitochondrial dysfunction, and especially dysfunction of ~~[[Metabolic flexibility\|~~mitochondrial dynamics]], is considered a hallmark of aging and has been implicated in age-related diseases such as osteoporosis or [[Aging and Neurodegeneration\|Alzheimer’s and Parkinson’s disease]]<ref name=":2">Age-related mitochondrial dysfunction as a key factor in COVID-19 disease. (2020). ''Experimental Gerontology, 142'', 111147. <nowiki>https://doi.org/10.1016/j.exger.2020.111147</nowiki></ref><ref name=":3">Chen, C., Turnbull, D. M., & Reeve, A. K. (2019). Mitochondrial dysfunction in Parkinson’s disease—Cause or consequence? ''Biology, 8''(2). <nowiki>https://doi.org/10.3390/biology8020038</nowiki></ref><ref name=":4">López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. ''Cell, 153''(6), 1194–1217. <nowiki>https://doi.org/10.1016/j.cell.2013.05.039</nowiki></ref><ref name=":20">Weir, H., Yao, P., Huynh, F., Escoubas, C., Goncalves, R., & Burkewitz, K. et al. (2017). Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling. ''Cell Metabolism'', ''26''(6), 884-896.e5. doi: 10.1016/j.cmet.2017.09.024</ref>. [[Mitochondria]] are highly dynamic organelles that undergo coordinated cycles of fission and fusion in order to maintain their shape, distribution and size, as shown by imaging studies in live cells<ref>Okamoto, K., & Shaw, J. (2005). Mitochondrial Morphology and Dynamics in Yeast and Multicellular Eukaryotes. ''Annual Review Of Genetics'', ''39''(1), 503-536. doi: 10.1146/annurev.genet.38.072902.093019</ref>. These dynamical processes are key for regulating organismal homeostasis and are required to maintain appropriate [[metabolic flexibility]]<ref>Tilokani, L., Nagashima, S., Paupe, V., & Prudent, J. (2018). Mitochondrial dynamics: overview of molecular mechanisms. ''Essays In Biochemistry'', ''62''(3), 341-360. doi: 10.1042/ebc20170104</ref>.		Mitochondrial dysfunction, and especially dysfunction of mitochondrial dynamics, is considered a hallmark of aging and has been implicated in age-related diseases such as osteoporosis or [[Aging and Neurodegeneration\|Alzheimer’s and Parkinson’s disease]]<ref name=":2">Age-related mitochondrial dysfunction as a key factor in COVID-19 disease. (2020). ''Experimental Gerontology, 142'', 111147. <nowiki>https://doi.org/10.1016/j.exger.2020.111147</nowiki></ref><ref name=":3">Chen, C., Turnbull, D. M., & Reeve, A. K. (2019). Mitochondrial dysfunction in Parkinson’s disease—Cause or consequence? ''Biology, 8''(2). <nowiki>https://doi.org/10.3390/biology8020038</nowiki></ref><ref name=":4">López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. ''Cell, 153''(6), 1194–1217. <nowiki>https://doi.org/10.1016/j.cell.2013.05.039</nowiki></ref><ref name=":20">Weir, H., Yao, P., Huynh, F., Escoubas, C., Goncalves, R., & Burkewitz, K. et al. (2017). Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling. ''Cell Metabolism'', ''26''(6), 884-896.e5. doi: 10.1016/j.cmet.2017.09.024</ref>. [[Mitochondria]] are highly dynamic organelles that undergo coordinated cycles of fission and fusion in order to maintain their shape, distribution and size, as shown by imaging studies in live cells<ref>Okamoto, K., & Shaw, J. (2005). Mitochondrial Morphology and Dynamics in Yeast and Multicellular Eukaryotes. ''Annual Review Of Genetics'', ''39''(1), 503-536. doi: 10.1146/annurev.genet.38.072902.093019</ref>. These dynamical processes are key for regulating organismal homeostasis and are required to maintain appropriate [[metabolic flexibility]]<ref>Tilokani, L., Nagashima, S., Paupe, V., & Prudent, J. (2018). Mitochondrial dynamics: overview of molecular mechanisms. ''Essays In Biochemistry'', ''62''(3), 341-360. doi: 10.1042/ebc20170104</ref>.

	== Basics of mitochondria ==		== Basics of mitochondria ==

Geroscientist: /* Mitochondrial dynamics */

2022-06-11T05:09:32Z

Mitochondrial dynamics

← Older revision		Revision as of 05:09, 11 June 2022
Line 31:		Line 31:

	== Mitochondrial dynamics ==		== Mitochondrial dynamics ==
	During aging, mitochondria acquire a less structured morphology and there is a progressive loss of network connectivity as well as mitochondria content<ref name=":20" />. Work from the Mair lab showed that [[Calorie restriction\|dietary restriction]] and constitutive activation of AMPK in C. ''elegans'' leads to a more youthful mitochondrial morphology ~~and requires of~~ mitochondrial fusion in peripheral tissues ~~for the associated lifespan increase~~<ref name=":20" />. Importantly, they showed that enhancing fusion itself is not able to increase lifespan, but that maintaining mitochondrial network homeostasis is sufficient for lifespan extension. By blocking certain components of the mitochondrial machinery and subjecting worms to different dietary interventions and then measuring their lifespans, they showed that the requirement for mitochondrial dynamics appears to be highly context-specific. For instance, intermittent fasting (IF) requires of functional mitochondrial dynamics for its associated lifespan extension phenotype. However, chronic dietary restriction without IF still leads to lifespan extension regardless of impaired mitochondrial dynamics<ref name=":20" />.		During aging, mitochondria acquire a less structured morphology and there is a progressive loss of network connectivity as well as mitochondria content.<ref name=":20" /> Work from the Mair lab showed that [[Calorie restriction\|dietary restriction]] and constitutive activation of AMPK in C. ''elegans'' leads to a more youthful mitochondrial morphology. The resulting lifespan increase in these worms was shown to require mitochondrial fusion in peripheral tissues.<ref name=":20" /> Importantly, they showed that enhancing fusion itself is not able to increase lifespan, but that maintaining mitochondrial network homeostasis is sufficient for lifespan extension. By blocking certain components of the mitochondrial machinery and subjecting worms to different dietary interventions and then measuring their lifespans, they showed that the requirement for mitochondrial dynamics appears to be highly context-specific. For instance, intermittent fasting (IF) requires functional mitochondrial dynamics for its associated lifespan extension phenotype. However, chronic dietary restriction without IF still leads to lifespan extension regardless of impaired mitochondrial dynamics.<ref name=":20" />

	== Mitochondrial dysfunction in disease ==		== Mitochondrial dysfunction in disease ==