Cold Therapy

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David Sinclair mentioned in ^[1] that he has a bed that you can control the temperature and he sets it a bit cooler duing the night

Todo

2011, Using Drosophila melanogaster to study the positive effects of mild stress on aging ^[2]
2012, [Mild stress as a means to modulate aging: from fly to human?] ^[3]
2013, Life extension after heat shock exposure: assessing meta-analytic evidence for hormesis ^[4]
2023, Hormesis defines the limits of lifespan ^[5]
2020, A dose of experimental hormesis: When mild stress protects and improves animal performance ^[6]
2023, Cold temperature extends longevity and prevents disease-related protein aggregation through PA28γ-induced proteasomes ^[7]

References

↑ 2022-09-02 - Interview Dr. David Sinclair - Optimize Longevity - Keeping Your Brain Young
↑ Le Bourg E: Using Drosophila melanogaster to study the positive effects of mild stress on aging. Exp Gerontol 2011. (PMID 20727961) [PubMed] [DOI] Several studies in the fly Drosophila melanogaster have shown that a mild stress can increase longevity, resistance to strong stresses (e.g., heat, fungal infection, cold) and delay behavioral aging. However, not all mild stresses have similar effects on the various studied traits. For instance, exposure to cold increases resistance to a fungal infection, but hypergravity and heat shocks do not. In addition to studies in flies and other invertebrates, it is necessary to perform experiments in mammals, to know whether mild stress could be used in therapy more thoroughly than today.
↑ Le Bourg É: [Mild stress as a means to modulate aging: from fly to human?]. Med Sci (Paris) 2012. (PMID 22480655) [PubMed] [DOI] Hormesis is the phenomenon by which adaptive responses to low doses of otherwise harmful conditions improve the functional ability of organisms. Some mild stresses have beneficial effects on longevity, aging and resistance to strong stresses (heat or cold shocks, infection) in Drosophila flies. Studies on rodents are indeed scarce but mild stress seems to be effective in humans because, for instance, patients suffering from angina have a higher survival when confronted with a heart attack. A few studies, in less tragic situations however, suggest that mild stress could have positive effects in elderly people. Performing more experiments on the effects of mild stress in humans would help to know whether it could be used in therapy or to improve healthspan of elderly.
↑ Lagisz M et al.: Life extension after heat shock exposure: assessing meta-analytic evidence for hormesis. Ageing Res Rev 2013. (PMID 23570942) [PubMed] [DOI] Hormesis is the response of organisms to a mild stressor resulting in improved health and longevity. Mild heat shocks have been thought to induce hormetic response because they promote increased activity of heat shock proteins (HSPs), which may extend lifespan. Using data from 27 studies on 12 animal species, we performed a comparative meta-analysis to quantify the effect of heat shock exposure on longevity. Contrary to our expectations, heat shock did not measurably increase longevity in the overall meta-analysis, although we observed much heterogeneity among studies. Thus, we explored the relative contributions of different experimental variables (i.e. moderators). Higher temperatures, longer durations of heat shock exposure, increased shock repeat and less time between repeat shocks, all decreased the likelihood of a life-extending effect, as would be expected when a hormetic response crosses the threshold to being a damaging exposure. We conclude that there is limited evidence that mild heat stress is a universal way of promoting longevity at the whole-organism level. Life extension via heat-induced hormesis is likely to be constrained to a narrow parameter window of experimental conditions.
↑ Calabrese EJ et al.: Hormesis defines the limits of lifespan. Ageing Res Rev 2023. (PMID 37709054) [PubMed] [DOI] This commentary provides a novel synthesis of how biological systems adapt to a broad spectrum of environmental and age-related stresses that are underlying causes of numerous degenerative diseases and debilitating effects of aging. It proposes that the most fundamental, evolutionary-based integrative strategy to sustain and protect health is based on the concept of hormesis. This concept integrates anti-oxidant, anti-inflammatory and cellular repair responses at all levels of biological organization (i.e., cell, organ and organism) within the framework of biphasic dose responses that describe the quantitative limits of biological plasticity in all cells and organisms from bacteria and plants to humans. A major feature of the hormetic concept is that low levels of biological, chemical, physical and psychological stress upregulate adaptive responses that not only precondition, repair and restore normal functions to damaged tissues/organs but modestly overcompensate, reducing ongoing background damage, thereby enhancing health beyond that in control groups, lacking the low level "beneficial" stress. Higher doses of such stress often become counterproductive and eventually harmful. Hormesis is active throughout the life-cycle and can be diminished by aging processes affecting the onset and severity of debilitating conditions/diseases, especially in elderly subjects. The most significant feature of the hormetic dose response is that the limits of biological plasticity for adaptive processes are less than twice that of control group responses, with most, at maximum, being 30-60 % greater than control group values. Yet, these modest increases can make the difference between health or disease and living or dying. The quantitative features of these adaptive hormetic dose responses are also independent of mechanism. These features of the hormetic dose response determine the capacity to which systems can adapt/be protected, the extent to which biological performance (e.g., memory, resistance to injury/disease, wound healing, hair growth or lifespan) can be enhanced/extended and the extent to which synergistic interactions may occur. Hormesis defines the quantitative rules within which adaptive processes operate and is central to evolution and biology and should become transformational for experimental concepts and study design strategies, public health practices and a vast range of therapeutic strategies and interventions.
↑ Berry R & López-Martínez G: A dose of experimental hormesis: When mild stress protects and improves animal performance. Comp Biochem Physiol A Mol Integr Physiol 2020. (PMID 31954863) [PubMed] [DOI] [Full text] The adaptive response characterized by a biphasic curve is known as hormesis. In a hormesis framework, exposure to low doses leads to protective and beneficial responses while exposures to high doses are damaging and detrimental. Comparative physiologists have studied hormesis for over a century, but our understanding of hormesis is fragmented due to rifts in consensus and taxonomic-specific terminology. Hormesis has been and is currently known by multiple names; preconditioning, conditioning, pretreatment, cross tolerance, adaptive homeostasis, and rapid stress hardening (mostly low temperature: rapid cold hardening). These are the most common names used to describe adaptive stress responses in animals. These responses are mechanistically similar, while having stress-specific responses, but they all can fall under the umbrella of hormesis. Here we review how hormesis studies have revealed animal performance benefits in response to changes in oxygen, temperature, ionizing radiation, heavy metals, pesticides, dehydration, gravity, and crowding. And how almost universally, hormetic responses are characterized by increases in performance that include either increases in reproduction, longevity, or both. And while the field can benefit from additional mechanistic work, we know that many of these responses are rooted in increases of antioxidants and oxidative stress protective mechanisms; including heat shock proteins. There is a clear, yet not fully elucidated, overlap between hormesis and the preparation for oxidative stress theory; which predicts part of the responses associated with hormesis. We discuss this, and the need for additional work into animal hormetic effects particularly focusing on the cost of hormesis.
↑ Lee HJ et al.: Cold temperature extends longevity and prevents disease-related protein aggregation through PA28γ-induced proteasomes. Nat Aging 2023. (PMID 37118550) [PubMed] [DOI] [Full text] Aging is a primary risk factor for neurodegenerative disorders that involve protein aggregation. Because lowering body temperature is one of the most effective mechanisms to extend longevity in both poikilotherms and homeotherms, a better understanding of cold-induced changes can lead to converging modifiers of pathological protein aggregation. Here, we find that cold temperature (15 °C) selectively induces the trypsin-like activity of the proteasome in Caenorhabditis elegans through PSME-3, the worm orthologue of human PA28γ/PSME3. This proteasome activator is required for cold-induced longevity and ameliorates age-related deficits in protein degradation. Moreover, cold-induced PA28γ/PSME-3 diminishes protein aggregation in C. elegans models of age-related diseases such as Huntington's and amyotrophic lateral sclerosis. Notably, exposure of human cells to moderate cold temperature (36 °C) also activates trypsin-like activity through PA28γ/PSME3, reducing disease-related protein aggregation and neurodegeneration. Together, our findings reveal a beneficial role of cold temperature that crosses evolutionary boundaries with potential implications for multi-disease prevention.

[1] 2022-09-02 - Interview Dr. David Sinclair - Optimize Longevity - Keeping Your Brain Young

[pmid20727961-2] Le Bourg E: Using Drosophila melanogaster to study the positive effects of mild stress on aging. Exp Gerontol 2011. (PMID 20727961) [PubMed] [DOI] Several studies in the fly Drosophila melanogaster have shown that a mild stress can increase longevity, resistance to strong stresses (e.g., heat, fungal infection, cold) and delay behavioral aging. However, not all mild stresses have similar effects on the various studied traits. For instance, exposure to cold increases resistance to a fungal infection, but hypergravity and heat shocks do not. In addition to studies in flies and other invertebrates, it is necessary to perform experiments in mammals, to know whether mild stress could be used in therapy more thoroughly than today.

[pmid22480655-3] Le Bourg É: [Mild stress as a means to modulate aging: from fly to human?]. Med Sci (Paris) 2012. (PMID 22480655) [PubMed] [DOI] Hormesis is the phenomenon by which adaptive responses to low doses of otherwise harmful conditions improve the functional ability of organisms. Some mild stresses have beneficial effects on longevity, aging and resistance to strong stresses (heat or cold shocks, infection) in Drosophila flies. Studies on rodents are indeed scarce but mild stress seems to be effective in humans because, for instance, patients suffering from angina have a higher survival when confronted with a heart attack. A few studies, in less tragic situations however, suggest that mild stress could have positive effects in elderly people. Performing more experiments on the effects of mild stress in humans would help to know whether it could be used in therapy or to improve healthspan of elderly.

[pmid23570942-4] Lagisz M et al.: Life extension after heat shock exposure: assessing meta-analytic evidence for hormesis. Ageing Res Rev 2013. (PMID 23570942) [PubMed] [DOI] Hormesis is the response of organisms to a mild stressor resulting in improved health and longevity. Mild heat shocks have been thought to induce hormetic response because they promote increased activity of heat shock proteins (HSPs), which may extend lifespan. Using data from 27 studies on 12 animal species, we performed a comparative meta-analysis to quantify the effect of heat shock exposure on longevity. Contrary to our expectations, heat shock did not measurably increase longevity in the overall meta-analysis, although we observed much heterogeneity among studies. Thus, we explored the relative contributions of different experimental variables (i.e. moderators). Higher temperatures, longer durations of heat shock exposure, increased shock repeat and less time between repeat shocks, all decreased the likelihood of a life-extending effect, as would be expected when a hormetic response crosses the threshold to being a damaging exposure. We conclude that there is limited evidence that mild heat stress is a universal way of promoting longevity at the whole-organism level. Life extension via heat-induced hormesis is likely to be constrained to a narrow parameter window of experimental conditions.

[pmid37709054-5] Calabrese EJ et al.: Hormesis defines the limits of lifespan. Ageing Res Rev 2023. (PMID 37709054) [PubMed] [DOI] This commentary provides a novel synthesis of how biological systems adapt to a broad spectrum of environmental and age-related stresses that are underlying causes of numerous degenerative diseases and debilitating effects of aging. It proposes that the most fundamental, evolutionary-based integrative strategy to sustain and protect health is based on the concept of hormesis. This concept integrates anti-oxidant, anti-inflammatory and cellular repair responses at all levels of biological organization (i.e., cell, organ and organism) within the framework of biphasic dose responses that describe the quantitative limits of biological plasticity in all cells and organisms from bacteria and plants to humans. A major feature of the hormetic concept is that low levels of biological, chemical, physical and psychological stress upregulate adaptive responses that not only precondition, repair and restore normal functions to damaged tissues/organs but modestly overcompensate, reducing ongoing background damage, thereby enhancing health beyond that in control groups, lacking the low level "beneficial" stress. Higher doses of such stress often become counterproductive and eventually harmful. Hormesis is active throughout the life-cycle and can be diminished by aging processes affecting the onset and severity of debilitating conditions/diseases, especially in elderly subjects. The most significant feature of the hormetic dose response is that the limits of biological plasticity for adaptive processes are less than twice that of control group responses, with most, at maximum, being 30-60 % greater than control group values. Yet, these modest increases can make the difference between health or disease and living or dying. The quantitative features of these adaptive hormetic dose responses are also independent of mechanism. These features of the hormetic dose response determine the capacity to which systems can adapt/be protected, the extent to which biological performance (e.g., memory, resistance to injury/disease, wound healing, hair growth or lifespan) can be enhanced/extended and the extent to which synergistic interactions may occur. Hormesis defines the quantitative rules within which adaptive processes operate and is central to evolution and biology and should become transformational for experimental concepts and study design strategies, public health practices and a vast range of therapeutic strategies and interventions.

[pmid31954863-6] Berry R & López-Martínez G: A dose of experimental hormesis: When mild stress protects and improves animal performance. Comp Biochem Physiol A Mol Integr Physiol 2020. (PMID 31954863) [PubMed] [DOI] [Full text] The adaptive response characterized by a biphasic curve is known as hormesis. In a hormesis framework, exposure to low doses leads to protective and beneficial responses while exposures to high doses are damaging and detrimental. Comparative physiologists have studied hormesis for over a century, but our understanding of hormesis is fragmented due to rifts in consensus and taxonomic-specific terminology. Hormesis has been and is currently known by multiple names; preconditioning, conditioning, pretreatment, cross tolerance, adaptive homeostasis, and rapid stress hardening (mostly low temperature: rapid cold hardening). These are the most common names used to describe adaptive stress responses in animals. These responses are mechanistically similar, while having stress-specific responses, but they all can fall under the umbrella of hormesis. Here we review how hormesis studies have revealed animal performance benefits in response to changes in oxygen, temperature, ionizing radiation, heavy metals, pesticides, dehydration, gravity, and crowding. And how almost universally, hormetic responses are characterized by increases in performance that include either increases in reproduction, longevity, or both. And while the field can benefit from additional mechanistic work, we know that many of these responses are rooted in increases of antioxidants and oxidative stress protective mechanisms; including heat shock proteins. There is a clear, yet not fully elucidated, overlap between hormesis and the preparation for oxidative stress theory; which predicts part of the responses associated with hormesis. We discuss this, and the need for additional work into animal hormetic effects particularly focusing on the cost of hormesis.

[pmid37118550-7] Lee HJ et al.: Cold temperature extends longevity and prevents disease-related protein aggregation through PA28γ-induced proteasomes. Nat Aging 2023. (PMID 37118550) [PubMed] [DOI] [Full text] Aging is a primary risk factor for neurodegenerative disorders that involve protein aggregation. Because lowering body temperature is one of the most effective mechanisms to extend longevity in both poikilotherms and homeotherms, a better understanding of cold-induced changes can lead to converging modifiers of pathological protein aggregation. Here, we find that cold temperature (15 °C) selectively induces the trypsin-like activity of the proteasome in Caenorhabditis elegans through PSME-3, the worm orthologue of human PA28γ/PSME3. This proteasome activator is required for cold-induced longevity and ameliorates age-related deficits in protein degradation. Moreover, cold-induced PA28γ/PSME-3 diminishes protein aggregation in C. elegans models of age-related diseases such as Huntington's and amyotrophic lateral sclerosis. Notably, exposure of human cells to moderate cold temperature (36 °C) also activates trypsin-like activity through PA28γ/PSME3, reducing disease-related protein aggregation and neurodegeneration. Together, our findings reveal a beneficial role of cold temperature that crosses evolutionary boundaries with potential implications for multi-disease prevention.

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