Cold-shock response - Revision history

Andrea: Added sample sizes from recent studies

2023-03-06T22:11:18Z

Added sample sizes from recent studies

← Older revision		Revision as of 22:11, 6 March 2023
Line 16:		Line 16:
	Induction of CSPs may also lead to the '''activation of brown fat''', known to decrease with age. Brown fat is commonly referred to as "healthy fat," due to its high number of mitochondria and high energy efficiency, as well as a number of health benefits associated to brown fat activation, such as increased insulin sensitivity, or reduced cholesterol.<ref>Chung, N. The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue. Journal of Exercise Nutrition & Biochemistry (2017). <nowiki>https://doi.org/10.20463/jenb.2017.0020</nowiki></ref><ref>Imbeault, P. et al. Cold exposure increases adiponectin levels in men. Metabolism: Clinical and Experimental (2009). <nowiki>https://doi.org/10.1016/j.metabol.2008.11.017</nowiki></ref><ref>Hoeke, G. et al. Role of Brown fat in lipoprotein metabolism and atherosclerosis. Circ. Res. (2015). <nowiki>https://doi.org/10.1161/CIRCRESAHA.115.306647</nowiki></ref> Shivering during or after cold exposure also leads to the release of succinate from muscles, which further activates brown fat thermogenesis.		Induction of CSPs may also lead to the '''activation of brown fat''', known to decrease with age. Brown fat is commonly referred to as "healthy fat," due to its high number of mitochondria and high energy efficiency, as well as a number of health benefits associated to brown fat activation, such as increased insulin sensitivity, or reduced cholesterol.<ref>Chung, N. The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue. Journal of Exercise Nutrition & Biochemistry (2017). <nowiki>https://doi.org/10.20463/jenb.2017.0020</nowiki></ref><ref>Imbeault, P. et al. Cold exposure increases adiponectin levels in men. Metabolism: Clinical and Experimental (2009). <nowiki>https://doi.org/10.1016/j.metabol.2008.11.017</nowiki></ref><ref>Hoeke, G. et al. Role of Brown fat in lipoprotein metabolism and atherosclerosis. Circ. Res. (2015). <nowiki>https://doi.org/10.1161/CIRCRESAHA.115.306647</nowiki></ref> Shivering during or after cold exposure also leads to the release of succinate from muscles, which further activates brown fat thermogenesis.

	A recent study in military personnel, demonstrated the beneficial impact of cold-shocks in '''mental health as well as physical composition''' of soldiers, after 8 weeks of regular cold exposure (indoors and outdoors).<ref name=":0">Néma J, Zdara J, Lašák P, Bavlovič J, Bureš M, Pejchal J, Schvach H. Impact of cold exposure on life satisfaction and physical composition of soldiers. BMJ Mil Health. 2023 Jan 4:e002237. doi: 10.1136/military-2022-002237. Epub ahead of print. PMID: 36599485.</ref> The cold immersion protocol consisted of 2 minutes cold immersions up to the neck (ie. with the head above the water) and 30-seconds cold showers for 5 times a week. Soldiers undergoing cold water immersions experienced a significant decrease in self-reported anxiety, an increase in self-reported wellbeing and sexual satisfaction, and a decrease in waist circumference and abdominal fat, all of which were not observed in the soldier control group. The only exception was changes in body fat composition in women soldiers, which remained unaltered compared to the control women soldier group.<ref name=":0" /> Importantly, these health benefits appeared to remain stable, and not only after immediate response to cold exposure.		A recent study in military personnel, demonstrated the beneficial impact of cold-shocks in '''mental health as well as physical composition''' of soldiers, after 8 weeks of regular cold exposure (indoors and outdoors).<ref name=":0">Néma J, Zdara J, Lašák P, Bavlovič J, Bureš M, Pejchal J, Schvach H. Impact of cold exposure on life satisfaction and physical composition of soldiers. BMJ Mil Health. 2023 Jan 4:e002237. doi: 10.1136/military-2022-002237. Epub ahead of print. PMID: 36599485.</ref> The cold immersion protocol consisted of 2 minutes cold immersions up to the neck (ie. with the head above the water) and 30-seconds cold showers for 5 times a week. Soldiers undergoing cold water immersions experienced a significant decrease in self-reported anxiety, an increase in self-reported wellbeing and sexual satisfaction, and a decrease in waist circumference and abdominal fat, all of which were not observed in the soldier control group. The only exception was changes in body fat composition in women soldiers, which remained unaltered compared to the control women soldier group.<ref name=":0" /> Importantly, these health benefits appeared to remain stable, and not only after immediate response to cold exposure. However, this study had a sample size of 49 participants and had reportedly borderline p-values. More exhaustive studies are needed to precisely estimate the mental and physical benefits of cold exposure.

	~~However~~, cold-shocks can be dangerous in some situations, as it can cause a '''heart attack''' due to severe vasoconstriction or hypothermia.<ref>Staff. "4 Phases of Cold Water Immersion". ''Beyond Cold Water Bootcamp''. Canadian Safe Boating Council. </ref>		On the contrary, cold-shocks can be dangerous in some situations, as they can cause a '''heart attack''' due to severe vasoconstriction or hypothermia.<ref>Staff. "4 Phases of Cold Water Immersion". ''Beyond Cold Water Bootcamp''. Canadian Safe Boating Council. </ref>

	==== Protocols of cold exposure to maximise health benefits ====		==== Protocols of cold exposure to maximise health benefits ====
Line 26:		Line 26:

	===== Duration =====		===== Duration =====
	The duration of cold exposure is critical, and it is ultimately tied to the temperature of the water (as discussed below). Most studies report health benefits after periodic 30 seconds to 2 minutes of cold exposure.<ref name=":0" /><ref name=":1">Søberg S, Löfgren J, Philipsen FE, Jensen M, Hansen AE, Ahrens E, Nystrup KB, Nielsen RD, Sølling C, Wedell-Neergaard AS, Berntsen M, Loft A, Kjær A, Gerhart-Hines Z, Johannesen HH, Pedersen BK, Karstoft K, Scheele C. Altered brown fat thermoregulation and enhanced cold-induced thermogenesis in young, healthy, winter-swimming men. Cell Rep Med. 2021 Oct 11;2(10):100408. doi: 10.1016/j.xcrm.2021.100408. PMID: 34755128; PMCID: PMC8561167.</ref> Some cold exposure researchers suggest a total of 11 minutes per week across sessions (1 to 5 minutes per session, 2 to 4 times per week) for maximising health benefits.<ref name=":1" />		The duration of cold exposure is critical, and it is ultimately tied to the temperature of the water (as discussed below). Most studies report health benefits after periodic 30 seconds to 2 minutes of cold exposure.<ref name=":0" /><ref name=":1">Søberg S, Löfgren J, Philipsen FE, Jensen M, Hansen AE, Ahrens E, Nystrup KB, Nielsen RD, Sølling C, Wedell-Neergaard AS, Berntsen M, Loft A, Kjær A, Gerhart-Hines Z, Johannesen HH, Pedersen BK, Karstoft K, Scheele C. Altered brown fat thermoregulation and enhanced cold-induced thermogenesis in young, healthy, winter-swimming men. Cell Rep Med. 2021 Oct 11;2(10):100408. doi: 10.1016/j.xcrm.2021.100408. PMID: 34755128; PMCID: PMC8561167.</ref> Some cold exposure researchers suggest a total of 11 minutes per week across sessions (1 to 5 minutes per session, 2 to 4 times per week) for maximising health benefits.<ref name=":1" /> Of note, the aforementioned study had a total of 15 participants, and therefore higher powered data is needed for estimating the duration of cold exposure with the most beneficial health effects.

	===== Temperature =====		===== Temperature =====

Andrea: Re-organised and added new content

2023-03-05T16:57:05Z

Re-organised and added new content

← Older revision		Revision as of 16:57, 5 March 2023
Line 1:		Line 1:
	The cold-shock response is a physiological response that occurs in organisms when they are rapidly exposed to cold temperatures. This response is characterized by a number of physiological changes, including an increase in heart rate, blood pressure, and breathing rate, ~~as well~~ as the release of stress hormones such as adrenaline. These changes are thought to be an adaptive response to the sudden drop in temperature, as they help to increase heat production and conserve body heat.		The cold-shock response is a physiological response that occurs in organisms when they are rapidly exposed to cold temperatures. This response is characterized by a number of physiological changes, including an increase in heart rate, blood pressure and breathing rate. A number of health benefits are also associated to activation of the sympathetic nervous system, such as the release of stress hormones such as adrenaline (epinephrine) and noradrenaline (norepinephrine), as well as dopamine.<ref>Šrámek, P., Šimečková, M., Janský, L. ''et al.'' Human physiological responses to immersion into water of different temperatures. ''Eur J Appl Physiol'' 81, 436–442 (2000). <nowiki>https://doi.org/10.1007/s004210050065</nowiki></ref> These changes are thought to be an adaptive response to the sudden drop in temperature, some of they help to increase heat production and conserve body heat.

	During the cold-shock response, blood vessels in the skin constrict and blood flow is redirected to the core of the body to help maintain core temperature. The body also starts to shiver in order to generate heat. The cold-shock response may cause an immediate loss of breathing control, which can lead to hyperventilation or even drowning in cold water.		During the cold-shock response, blood vessels in the skin constrict and blood flow is redirected to the core of the body to help maintain core temperature. The body also starts to shiver in order to generate heat. The cold-shock response may cause an immediate loss of breathing control, which can lead to hyperventilation or even drowning in cold water.

	It is possible to become habituated to cold shocks, known as physiological conditioning. Naturally, people with higher amounts of body fat, diving experience or higher autonomic control of metabolism are able to become easier conditioned against cold shock.<ref>"Exercise in the Cold: Part II - A physiological trip through cold water exposure". ''The science of sport''. www.sportsscientists.com. 29 January 2008.</ref>		It is possible to become habituated to cold shocks, known as physiological conditioning. Naturally, people with higher amounts of body fat, diving experience or higher autonomic control of metabolism are able to become easier conditioned against cold shock.<ref>"Exercise in the Cold: Part II - A physiological trip through cold water exposure". ''The science of sport''. www.sportsscientists.com. 29 January 2008.</ref>

			=== History ===
			The first cold-shock protein (CSP) was identified in the 90s in ''E. coli'' after induction to cold-shock, and this and other CSPs have since been identified; they also appear to be evolutionary conserved across species.<ref>WISTOW, G. Cold shock and DNA binding. ''Nature'' 344, 823–824 (1990). <nowiki>https://doi.org/10.1038/344823c0</nowiki></ref><ref>Landsman, D. RNP-1, an RNA-binding motif is conserved in the DNA-binding cold shock domain. Nucleic Acids Research (1992). <nowiki>https://doi.org/10.1093/nar/20.11.2861</nowiki></ref> CSPs are essential for survival at cold temperatures and play a role in various stages of protein synthesis and [[proteostasis]] mechanisms.

	=== Hormesis ===		=== Hormesis ===
	The cold-shock response, ~~like~~ the [[heat-shock response]], is hypothesized to be a [[hormesis]] phenomenon, in which a beneficial effect may occur after exposure to low doses of a potentially harmful condition, which would otherwise be harmful if performed in higher doses.		The cold-shock response, similar to the [[heat-shock response]], is hypothesized to be a [[hormesis]] phenomenon, in which a beneficial effect may occur after exposure to low doses of a potentially harmful condition, which would otherwise be harmful if performed in higher doses.

			=== Health benefits ===
			Some of the aftermath benefits of cold-shock include the '''lowering of blood pressure, increase in insulin sensitivity and cortisol, boosting of the immune system and antidepressant effects'''.<ref>Knechtle B, Waśkiewicz Z, Sousa CV, Hill L, Nikolaidis PT. Cold Water Swimming-Benefits and Risks: A Narrative Review. Int J Environ Res Public Health. 2020 Dec 2;17(23):8984. doi: 10.3390/ijerph17238984. PMID: 33276648; PMCID: PMC7730683.</ref> It can also be beneficial in some situations, for instance to prevent heat stroke, or to aid with muscle recovery after injury or soreness.<ref>Tipton, M. J.; Collier, N.; Massey, H.; Corbett, J.; Harper, M. (2017-11-01). "Cold water immersion: kill or cure?: Cold water immersion: kill or cure?". ''Experimental Physiology''. '''102''' (11): 1335–1355. [[Doi (identifier)\|doi]]:10.1113/EP086283. [[PMID (identifier)\|PMID]] 28833689.</ref><ref>Moore, E., Fuller, J.T., Buckley, J.D. ''et al.'' Impact of Cold-Water Immersion Compared with Passive Recovery Following a Single Bout of Strenuous Exercise on Athletic Performance in Physically Active Participants: A Systematic Review with Meta-analysis and Meta-regression. ''Sports Med'' 52, 1667–1688 (2022). <nowiki>https://doi.org/10.1007/s40279-022-01644-9</nowiki></ref>

			Induction of CSPs may also lead to the '''activation of brown fat''', known to decrease with age. Brown fat is commonly referred to as "healthy fat," due to its high number of mitochondria and high energy efficiency, as well as a number of health benefits associated to brown fat activation, such as increased insulin sensitivity, or reduced cholesterol.<ref>Chung, N. The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue. Journal of Exercise Nutrition & Biochemistry (2017). <nowiki>https://doi.org/10.20463/jenb.2017.0020</nowiki></ref><ref>Imbeault, P. et al. Cold exposure increases adiponectin levels in men. Metabolism: Clinical and Experimental (2009). <nowiki>https://doi.org/10.1016/j.metabol.2008.11.017</nowiki></ref><ref>Hoeke, G. et al. Role of Brown fat in lipoprotein metabolism and atherosclerosis. Circ. Res. (2015). <nowiki>https://doi.org/10.1161/CIRCRESAHA.115.306647</nowiki></ref> Shivering during or after cold exposure also leads to the release of succinate from muscles, which further activates brown fat thermogenesis.

			A recent study in military personnel, demonstrated the beneficial impact of cold-shocks in '''mental health as well as physical composition''' of soldiers, after 8 weeks of regular cold exposure (indoors and outdoors).<ref name=":0">Néma J, Zdara J, Lašák P, Bavlovič J, Bureš M, Pejchal J, Schvach H. Impact of cold exposure on life satisfaction and physical composition of soldiers. BMJ Mil Health. 2023 Jan 4:e002237. doi: 10.1136/military-2022-002237. Epub ahead of print. PMID: 36599485.</ref> The cold immersion protocol consisted of 2 minutes cold immersions up to the neck (ie. with the head above the water) and 30-seconds cold showers for 5 times a week. Soldiers undergoing cold water immersions experienced a significant decrease in self-reported anxiety, an increase in self-reported wellbeing and sexual satisfaction, and a decrease in waist circumference and abdominal fat, all of which were not observed in the soldier control group. The only exception was changes in body fat composition in women soldiers, which remained unaltered compared to the control women soldier group.<ref name=":0" /> Importantly, these health benefits appeared to remain stable, and not only after immediate response to cold exposure.

			However, cold-shocks can be dangerous in some situations, as it can cause a '''heart attack''' due to severe vasoconstriction or hypothermia.<ref>Staff. "4 Phases of Cold Water Immersion". ''Beyond Cold Water Bootcamp''. Canadian Safe Boating Council. </ref>

			==== Protocols of cold exposure to maximise health benefits ====

	~~Some of~~ the ~~benefits~~ of cold~~-shock include the lowering of blood pressure~~, ~~increase~~ in ~~insulin sensitivity and cortisol~~, ~~boosting of the immune system and antidepressant effects~~.<ref>~~Knechtle B~~, ~~Waśkiewicz Z~~, ~~Sousa CV~~, ~~Hill L~~, ~~Nikolaidis PT~~. ~~Cold Water Swimming~~-~~Benefits~~ and ~~Risks: A Narrative Review~~. ~~Int~~ J ~~Environ Res Public Health~~. ~~2020 Dec 2~~;17(23):~~8984~~. doi: 10.~~3390~~/~~ijerph17238984~~. PMID: ~~33276648~~; PMCID: ~~PMC7730683~~.</ref> It ~~can also be beneficial~~ in ~~some situations~~, ~~for instance to quickly cool down to prevent heat stroke, or to aid with muscle recovery after injury or soreness~~.<ref>Tipton, M. J.; Collier, N.; Massey, H.; Corbett, J.; Harper, M. (2017-11-01). "Cold water immersion: kill or cure?: Cold water immersion: kill or cure?". ''Experimental Physiology''. '''102''' (11): 1335–1355. [[Doi (identifier)\|doi]]:10.1113/EP086283. [[PMID (identifier)\|PMID]] 28833689.</ref>		===== Timing =====
			An important point to consider is the timing of cold exposure. For instance, when training for increasing strength or hypertrophy, it is recommended to avoid deliberate cold exposure in the 6 to 8 hours after training, as it might lead to smaller long-term muscle gains.<ref>Roberts LA, Raastad T, Markworth JF, Figueiredo VC, Egner IM, Shield A, Cameron-Smith D, Coombes JS, Peake JM. Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training. J Physiol. 2015 Sep 15;593(18):4285-301. doi: 10.1113/JP270570. Epub 2015 Aug 13. PMID: 26174323; PMCID: PMC4594298.</ref> It is generally recommended to undergo cold exposure early in the morning, as the body heats up and might counteract sleep.

	~~However,~~ cold~~-shocks can be dangerous in some situations~~, as ~~it can cause a heart attack due~~ to ~~severe vasoconstriction or hypothermia~~.<ref>~~Staff.~~ "~~4 Phases of Cold Water Immersion~~". ~~''Beyond Cold Water Bootcamp''~~. ~~Canadian Safe Boating Council~~. </ref>		===== Duration =====
			The duration of cold exposure is critical, and it is ultimately tied to the temperature of the water (as discussed below). Most studies report health benefits after periodic 30 seconds to 2 minutes of cold exposure.<ref name=":0" /><ref name=":1">Søberg S, Löfgren J, Philipsen FE, Jensen M, Hansen AE, Ahrens E, Nystrup KB, Nielsen RD, Sølling C, Wedell-Neergaard AS, Berntsen M, Loft A, Kjær A, Gerhart-Hines Z, Johannesen HH, Pedersen BK, Karstoft K, Scheele C. Altered brown fat thermoregulation and enhanced cold-induced thermogenesis in young, healthy, winter-swimming men. Cell Rep Med. 2021 Oct 11;2(10):100408. doi: 10.1016/j.xcrm.2021.100408. PMID: 34755128; PMCID: PMC8561167.</ref> Some cold exposure researchers suggest a total of 11 minutes per week across sessions (1 to 5 minutes per session, 2 to 4 times per week) for maximising health benefits.<ref name=":1" />

	=== ~~Aging~~ ===		===== Temperature =====
	~~The first cold-shock protein (CSP) was identified in~~ the ~~90s in ''E~~. ~~coli'' after induction to cold-shock~~, ~~and this and other CSPs have shown to exist and~~ be ~~well conserved across evolution~~.~~<ref>WISTOW, G. Cold shock and DNA binding. ''Nature'' 344, 823–824~~ (~~1990~~)~~. <nowiki>https://doi.org/10.1038/344823c0</nowiki></ref><ref>Landsman, D. RNP-~~1, ~~an RNA-binding motif is conserved~~ in ~~the DNA-binding cold shock domain. Nucleic Acids Research~~ (~~1992~~). <~~nowiki>https~~:/~~/doi.org/10.1093/nar/20.11.2861</nowiki~~>~~</ref> They are essential for survival at cold temperatures and play a role in various stages of protein synthesis and [[proteostasis]] mechanisms.~~		Lastly, the temperature of water is also logically important to consider. In general, the colder the water, the shorter the duration of exposure should be. Some studies reported benefits in prolonged dopamine release after immersion in 15ºC (∼60ºF) water for up to 1 hour (with head always above water), while other studies described benefits in epinephrine release after only 20 seconds of 4ºC (∼40ºF) water exposure.<ref name=":1" />

	Similarly to [[Heat-shock response\|heat-shock proteins]], CSPs regulate a number of molecules involved in longevity pathways, such as NF-kB, p53 or TGF-B, involved in inflammation, senescence and fribosis, respectively.<ref>Lindquist, J.A. and Mertens, P.R. Cold shock proteins: from cellular mechanisms to pathophysiology and disease. Cell Commun Signal. (2018). <nowiki>https://doi.org/10.1186/s12964-018-0274-6</nowiki></ref> It may also lead to the activation of brown fat, known to decrease with age. Brown fat is commonly referred to as "healthy fat," due to its high number of mitochondria and high energy efficiency, as well as the number of health benefits associated to brown fat activation, such as increased insulin sensitivity, or reduced cholesterol.<ref>Chung, N. The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue. Journal of Exercise Nutrition & Biochemistry (2017). <nowiki>https://doi.org/10.20463/jenb.2017.0020</nowiki></ref><ref>Imbeault, P. et al. Cold exposure increases adiponectin levels in men. Metabolism: Clinical and Experimental (2009). <nowiki>https://doi.org/10.1016/j.metabol.2008.11.017</nowiki></ref><ref>Hoeke, G. et al. Role of Brown fat in lipoprotein metabolism and atherosclerosis. Circ. Res. (2015). <nowiki>https://doi.org/10.1161/CIRCRESAHA.115.306647</nowiki></ref> CSPS are suggested to be involved in ~~disease~~ onset and progression of a variety of age-related diseases.<ref>Lindquist, J.A. and Mertens, P.R. Cold shock proteins: from cellular mechanisms to pathophysiology and disease. Cell Commun Signal. (2018). <nowiki>https://doi.org/10.1186/s12964-018-0274-6</nowiki></ref>		=== Longevity ===
			Similarly to [[Heat-shock response\|heat-shock proteins]], CSPs regulate a number of molecules involved in longevity pathways, such as NF-kB, p53 or TGF-B, each involved in inflammation, senescence and fribosis, respectively.<ref>Lindquist, J.A. and Mertens, P.R. Cold shock proteins: from cellular mechanisms to pathophysiology and disease. Cell Commun Signal. (2018). <nowiki>https://doi.org/10.1186/s12964-018-0274-6</nowiki></ref> CSPS are also suggested to be involved in onset and progression of a variety of age-related diseases.<ref>Lindquist, J.A. and Mertens, P.R. Cold shock proteins: from cellular mechanisms to pathophysiology and disease. Cell Commun Signal. (2018). <nowiki>https://doi.org/10.1186/s12964-018-0274-6</nowiki></ref>

	Acute cold therapy has been suggested as a rejuvenation mechanism due to its [[hormesis]] effects, but as for now remains largely unproven and key studies in mammals are lacking. [[Fisetin]] supplementation has been suggested as a method to modulate CSPs activity.<ref>Khan, M.I. et al. YB-1 expression promotes epithelial-to-mesenchymal transition in prostate cancer that is inhibited by a small molecule fisetin. Oncotarget (2014). <nowiki>https://doi.org/10.18632/oncotarget.1790</nowiki></ref>		Acute cold therapy has been suggested as a rejuvenation mechanism due to its [[hormesis]] effects, but as for now remains largely unproven and key studies in mammals are lacking. [[Fisetin]] supplementation has been suggested as a method to modulate CSPs activity.<ref>Khan, M.I. et al. YB-1 expression promotes epithelial-to-mesenchymal transition in prostate cancer that is inhibited by a small molecule fisetin. Oncotarget (2014). <nowiki>https://doi.org/10.18632/oncotarget.1790</nowiki></ref>

Andrea: Added entry

2023-01-26T19:14:42Z

Added entry

New page

The cold-shock response is a physiological response that occurs in organisms when they are rapidly exposed to cold temperatures. This response is characterized by a number of physiological changes, including an increase in heart rate, blood pressure, and breathing rate, as well as the release of stress hormones such as adrenaline. These changes are thought to be an adaptive response to the sudden drop in temperature, as they help to increase heat production and conserve body heat.

During the cold-shock response, blood vessels in the skin constrict and blood flow is redirected to the core of the body to help maintain core temperature. The body also starts to shiver in order to generate heat. The cold-shock response may cause an immediate loss of breathing control, which can lead to hyperventilation or even drowning in cold water.

It is possible to become habituated to cold shocks, known as physiological conditioning. Naturally, people with higher amounts of body fat, diving experience or higher autonomic control of metabolism are able to become easier conditioned against cold shock.<ref>"Exercise in the Cold: Part II - A physiological trip through cold water exposure". ''The science of sport''. www.sportsscientists.com. 29 January 2008.</ref>

=== Hormesis ===
The cold-shock response, like the [[heat-shock response]], is hypothesized to be a [[hormesis]] phenomenon, in which a beneficial effect may occur after exposure to low doses of a potentially harmful condition, which would otherwise be harmful if performed in higher doses.

Some of the benefits of cold-shock include the lowering of blood pressure, increase in insulin sensitivity and cortisol, boosting of the immune system and antidepressant effects.<ref>Knechtle B, Waśkiewicz Z, Sousa CV, Hill L, Nikolaidis PT. Cold Water Swimming-Benefits and Risks: A Narrative Review. Int J Environ Res Public Health. 2020 Dec 2;17(23):8984. doi: 10.3390/ijerph17238984. PMID: 33276648; PMCID: PMC7730683.</ref> It can also be beneficial in some situations, for instance to quickly cool down to prevent heat stroke, or to aid with muscle recovery after injury or soreness.<ref>Tipton, M. J.; Collier, N.; Massey, H.; Corbett, J.; Harper, M. (2017-11-01). "Cold water immersion: kill or cure?: Cold water immersion: kill or cure?". ''Experimental Physiology''. '''102''' (11): 1335–1355. [[Doi (identifier)|doi]]:10.1113/EP086283. [[PMID (identifier)|PMID]] 28833689.</ref>

However, cold-shocks can be dangerous in some situations, as it can cause a heart attack due to severe vasoconstriction or hypothermia.<ref>Staff. "4 Phases of Cold Water Immersion". ''Beyond Cold Water Bootcamp''. Canadian Safe Boating Council. </ref>

=== Aging ===
The first cold-shock protein (CSP) was identified in the 90s in ''E. coli'' after induction to cold-shock, and this and other CSPs have shown to exist and be well conserved across evolution.<ref>WISTOW, G. Cold shock and DNA binding. ''Nature'' 344, 823–824 (1990). <nowiki>https://doi.org/10.1038/344823c0</nowiki></ref><ref>Landsman, D. RNP-1, an RNA-binding motif is conserved in the DNA-binding cold shock domain. Nucleic Acids Research (1992). <nowiki>https://doi.org/10.1093/nar/20.11.2861</nowiki></ref> They are essential for survival at cold temperatures and play a role in various stages of protein synthesis and [[proteostasis]] mechanisms.

Similarly to [[Heat-shock response|heat-shock proteins]], CSPs regulate a number of molecules involved in longevity pathways, such as NF-kB, p53 or TGF-B, involved in inflammation, senescence and fribosis, respectively.<ref>Lindquist, J.A. and Mertens, P.R. Cold shock proteins: from cellular mechanisms to pathophysiology and disease. Cell Commun Signal. (2018). <nowiki>https://doi.org/10.1186/s12964-018-0274-6</nowiki></ref> It may also lead to the activation of brown fat, known to decrease with age. Brown fat is commonly referred to as "healthy fat," due to its high number of mitochondria and high energy efficiency, as well as the number of health benefits associated to brown fat activation, such as increased insulin sensitivity, or reduced cholesterol.<ref>Chung, N. The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue. Journal of Exercise Nutrition & Biochemistry (2017). <nowiki>https://doi.org/10.20463/jenb.2017.0020</nowiki></ref><ref>Imbeault, P. et al. Cold exposure increases adiponectin levels in men. Metabolism: Clinical and Experimental (2009). <nowiki>https://doi.org/10.1016/j.metabol.2008.11.017</nowiki></ref><ref>Hoeke, G. et al. Role of Brown fat in lipoprotein metabolism and atherosclerosis. Circ. Res. (2015). <nowiki>https://doi.org/10.1161/CIRCRESAHA.115.306647</nowiki></ref> CSPS are suggested to be involved in disease onset and progression of a variety of age-related diseases.<ref>Lindquist, J.A. and Mertens, P.R. Cold shock proteins: from cellular mechanisms to pathophysiology and disease. Cell Commun Signal. (2018). <nowiki>https://doi.org/10.1186/s12964-018-0274-6</nowiki></ref>

Acute cold therapy has been suggested as a rejuvenation mechanism due to its [[hormesis]] effects, but as for now remains largely unproven and key studies in mammals are lacking. [[Fisetin]] supplementation has been suggested as a method to modulate CSPs activity.<ref>Khan, M.I. et al. YB-1 expression promotes epithelial-to-mesenchymal transition in prostate cancer that is inhibited by a small molecule fisetin. Oncotarget (2014). <nowiki>https://doi.org/10.18632/oncotarget.1790</nowiki></ref>
[[Category:Main list]]
[[Category:Aging pathways and hallmarks]]
[[Category:Lifespan interventions]]