Calorie restriction - Revision history

Dmitry Dzhagarov: /* Humans */

2024-07-28T18:46:29Z

Humans

← Older revision		Revision as of 18:46, 28 July 2024
Line 64:		Line 64:
	'''CALERIE trials'''		'''CALERIE trials'''

	The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) research network has produced one of the most rigorous clinical studies conducted in humans. Over a period of nine years, three pilot trials were conducted followed by a randomized study (CALERIE 2).<ref name=":1">Kraus, W. E., Bhapkar, M., Huffman, K. M., Pieper, C. F., Das, S. K., Redman, L. M., ... & CALERIE Investigators. (2019). 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial. ''The lancet Diabetes & endocrinology'', ''7''(9), 673-683.</ref><ref name=":2">Rickman, A. D., Williamson, D. A., Martin, C. K., Gilhooly, C. H., Stein, R. I., Bales, C. W., ... & Das, S. K. (2011). The CALERIE Study: design and methods of an innovative 25% caloric restriction intervention. ''Contemporary clinical trials'', ''32''(6), 874-881.</ref>		The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) research network has produced one of the most rigorous clinical studies conducted in humans. It started with clinical study involving 2 years of sustained 25% calorie restriction in men aged 21–50 years and women aged 21–47 years that aims to explore whether sustained calorie restriction can extend lifespan, improve metabolic health, and potentially delay the onset of age-related conditions. Two years of sustained CR in humans positively affected skeletal muscle quality, and impacted gene expression and splicing profiles of biological pathways affected by CR in model organisms, suggesting that attainable levels of CR in a lifestyle intervention can benefit muscle health in humans.<ref>Das, J. K., Banskota, N., Candia, J., Griswold, M. E., Orenduff, M., de Cabo, R., ... & Ferrucci, L. (2023). Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study. Aging cell, 22(12), e13963. PMID: 37823711 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10726900/ PMC10726900] DOI: 10.1111/acel.13963</ref> CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various [[Epigenetic clock\|DNAm clocks]] including PhenoAge and GrimAge.<ref>PMID: 37118425 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148951/ PMC10148951] DOI: 10.1038/s43587-022-00357-y</ref>

			Over a period of nine years, three pilot trials were conducted followed by a randomized study (CALERIE 2).<ref name=":1">Kraus, W. E., Bhapkar, M., Huffman, K. M., Pieper, C. F., Das, S. K., Redman, L. M., ... & CALERIE Investigators. (2019). 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial. ''The lancet Diabetes & endocrinology'', ''7''(9), 673-683.</ref><ref name=":2">Rickman, A. D., Williamson, D. A., Martin, C. K., Gilhooly, C. H., Stein, R. I., Bales, C. W., ... & Das, S. K. (2011). The CALERIE Study: design and methods of an innovative 25% caloric restriction intervention. ''Contemporary clinical trials'', ''32''(6), 874-881.</ref>
			(CALERIE™) 2 trial tested randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.0-27.9 kg/m2), to 25% CR or ad-libitum (AL) control (2:1) for 2 years to test effects of CR on telomere length (TL) attrition. TL was quantified in blood samples collected at baseline, 12-, and 24-months by quantitative PCR (absolute TL; aTL). No differences were observed when considering TL change across the study duration from baseline to 24-months.<ref>Hastings, W. J., Ye, Q., Wolf, S. E., Ryan, C. P., Das, S. K., Huffman, K. M., ... & Shalev, I. (2024). Effect of long‐term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis. Aging cell, e14149. PMID: 38504468 [https://doi.org/10.1111/acel.14149 DOI: 10.1111/acel.14149]</ref>

	During phase 1 of the trial, three differing degrees of CR (20%, 25%, and 30%) were tested in a variety of age groups with an overweight BMI status. The trial lasted for 6 – 12 months, and the studies were used to develop and advance the following Phase 2 trial.		During phase 1 of the trial, three differing degrees of CR (20%, 25%, and 30%) were tested in a variety of age groups with an overweight BMI status. The trial lasted for 6 – 12 months, and the studies were used to develop and advance the following Phase 2 trial.

Dmitry Dzhagarov: /* Underlying biological mechanisms */

2023-12-14T07:21:13Z

Underlying biological mechanisms

← Older revision		Revision as of 07:21, 14 December 2023
Line 77:		Line 77:

	== Underlying biological mechanisms ==		== Underlying biological mechanisms ==
			[[File:The two primary molecular regulators of lifespan.jpg\|thumb\|The two primary molecular regulators of lifespan in case of food shortage or its pharmacological imitation. According to an article by Packer M.<ref>Packer, M. (2020). Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure. European Heart Journal, 41(39), 3856-3861. PMID: 32460327 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599035/ PMC7599035] DOI: 10.1093/eurheartj/ehaa360</ref>]]
	Consuming extra calories can lead to cellular glycotoxicity and lipotoxicity, which causes inflammation and oxidative stress and thus increases the risk of age-related diseases (e.g. cancer, diabetes, cardiovascular disorders).<ref name=":0" /> Some proposed health benefits of CR include preservation of cognition, protection of colon health and reduced risk of arthritis, amongst others.		Consuming extra calories can lead to cellular glycotoxicity and lipotoxicity, which causes inflammation and oxidative stress and thus increases the risk of age-related diseases (e.g. cancer, diabetes, cardiovascular disorders).<ref name=":0" /> Some proposed health benefits of CR include preservation of cognition, protection of colon health and reduced risk of arthritis, amongst others.

Andrea: category change

2022-12-28T08:48:41Z

category change

← Older revision		Revision as of 08:48, 28 December 2022
Line 155:		Line 155:
	== References ==		== References ==
	<references />		<references />
	~~[[Category:Pillar Articles]]~~
	[[Category:Main list]]		[[Category:Main list]]
	[[Category:Lifespan interventions]]		[[Category:Lifespan interventions]]
			[[Category:Fundamentals]]

Andrea: category change

2022-12-27T11:59:48Z

category change

← Older revision		Revision as of 11:59, 27 December 2022
Line 156:		Line 156:
	<references />		<references />
	[[Category:Pillar Articles]]		[[Category:Pillar Articles]]
	[[Category:~~Longevity~~]]		[[Category:Main list]]
			[[Category:Lifespan interventions]]

Dmitry Dzhagarov: /* Controversies of calorie restriction research */

2022-12-24T19:13:48Z

Controversies of calorie restriction research

← Older revision		Revision as of 19:13, 24 December 2022
Line 151:		Line 151:

	Similar to non-human primates, the effects of CR on lifespan remain controversial in humans. However, what seems clear from obesity studies is that eating too much results in poor health and decreased longevity.<ref>Pifferi, F., Terrien, J., Marchal, J., Dal-Pan, A., Djelti, F., Hardy, I., Chahory, S., Cordonnier, N., Desquilbet, L., Hurion, M. and Zahariev, A., 2018. Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates. ''Communications biology'', ''1''(1), pp.1-8.</ref>		Similar to non-human primates, the effects of CR on lifespan remain controversial in humans. However, what seems clear from obesity studies is that eating too much results in poor health and decreased longevity.<ref>Pifferi, F., Terrien, J., Marchal, J., Dal-Pan, A., Djelti, F., Hardy, I., Chahory, S., Cordonnier, N., Desquilbet, L., Hurion, M. and Zahariev, A., 2018. Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates. ''Communications biology'', ''1''(1), pp.1-8.</ref>


			== References ==
	<references />		<references />
			[[Category:Pillar Articles]]
	[[Category:Longevity]]		[[Category:Longevity]]

Dmitry Dzhagarov: /* CR and Intermittent Fasting */

2022-12-05T10:27:25Z

CR and Intermittent Fasting

← Older revision		Revision as of 10:27, 5 December 2022
Line 126:		Line 126:
	Intermittent fasting (IF) has attained popular interest in recent years for its various potential health benefits, including for treating disease and extending lifespan.<ref>Lee, M. B., Hill, C. M., Bitto, A., & Kaeberlein, M. (2021). Antiaging diets: Separating fact from fiction. ''Science'', ''374''(6570), eabe7365.		Intermittent fasting (IF) has attained popular interest in recent years for its various potential health benefits, including for treating disease and extending lifespan.<ref>Lee, M. B., Hill, C. M., Bitto, A., & Kaeberlein, M. (2021). Antiaging diets: Separating fact from fiction. ''Science'', ''374''(6570), eabe7365.

	Chicago</ref><ref name=":10">Longo, V. D., Di Tano, M., Mattson, M. P., & Guidi, N. (2021). Intermittent and periodic fasting, longevity and disease. ''Nature aging'', ''1''(1), 47-59.</ref> Some preclinical evidence shows that certain IF regimens can prevent the onset of many age-related diseases. However, IF is not always associated with benefits in healthspan and may increase or decrease lifespan.<ref name=":10" /> It has been proposed that at least part of the lifespan extending effect of CR in humans is related to fasting, and in rodents fasting is required for a CR diet to protect from frailty and extend lifespan.<ref name=":10" /><ref>Pak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., ... & Lamming, D. W. (2021). Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice. ''Nature metabolism'', ''3''(10), 1327-1341.</ref> In rodent models, the evidence for IF preventing cancer development or growth is ambiguous, with studies showing no effect or potential harm with IF. More studies are required to better understand IF, both for preclinical and clinical research.<ref>Clifton, K. K., Ma, C. X., Fontana, L., & Peterson, L. L. (2021). Intermittent fasting in the prevention and treatment of cancer. ''CA: a cancer journal for clinicians'', ''71''(6), 527-546.</ref>		Chicago</ref><ref name=":10">Longo, V. D., Di Tano, M., Mattson, M. P., & Guidi, N. (2021). Intermittent and periodic fasting, longevity and disease. ''Nature aging'', ''1''(1), 47-59.</ref> Some preclinical evidence shows that certain IF regimens can prevent the onset of many age-related diseases. However, IF is not always associated with benefits in healthspan and may increase or decrease lifespan.<ref name=":10" /> It has been proposed that at least part of the lifespan extending effect of CR in humans is related to fasting, and in rodents fasting is required for a CR diet to protect from [[frailty]] and extend lifespan.<ref name=":10" /><ref>Pak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., ... & Lamming, D. W. (2021). Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice. ''Nature metabolism'', ''3''(10), 1327-1341.</ref> In rodent models, the evidence for IF preventing cancer development or growth is ambiguous, with studies showing no effect or potential harm with IF. More studies are required to better understand IF, both for preclinical and clinical research.<ref>Clifton, K. K., Ma, C. X., Fontana, L., & Peterson, L. L. (2021). Intermittent fasting in the prevention and treatment of cancer. ''CA: a cancer journal for clinicians'', ''71''(6), 527-546.</ref>

	A recent study in China randomized 139 obese adults to either calorie restriction alone or to calorie restriction with time-restricted eating (a 16-hour intermittent fast and a 8-hour period for eating).<ref>Liu, D., Huang, Y., Huang, C., Yang, S., Wei, X., & Zhang, P. et al. (2022). Calorie Restriction with or without Time-Restricted Eating in Weight Loss. ''New England Journal Of Medicine'', ''386''(16), 1495-1504. doi: 10.1056/nejmoa2114833</ref> After one year, both groups had lost 7-10% of body weight and showed healthier markers for blood sugar, blood fat levels and insulin sensitivity. Importantly, there was no statistically significant difference between both groups, suggesting calorie restriction is responsible for the health-associated benefits and that intermittent fasting has no added benefits to CR diets.		A recent study in China randomized 139 obese adults to either calorie restriction alone or to calorie restriction with time-restricted eating (a 16-hour intermittent fast and a 8-hour period for eating).<ref>Liu, D., Huang, Y., Huang, C., Yang, S., Wei, X., & Zhang, P. et al. (2022). Calorie Restriction with or without Time-Restricted Eating in Weight Loss. ''New England Journal Of Medicine'', ''386''(16), 1495-1504. doi: 10.1056/nejmoa2114833</ref> After one year, both groups had lost 7-10% of body weight and showed healthier markers for blood sugar, blood fat levels and insulin sensitivity. Importantly, there was no statistically significant difference between both groups, suggesting calorie restriction is responsible for the health-associated benefits and that intermittent fasting has no added benefits to CR diets.

	===== 5. How long should CR interventions last? =====		===== 5. How long should CR interventions last? =====

Rapacurious: /* CR and Intermittent Fasting */

2022-08-14T15:36:20Z

CR and Intermittent Fasting

← Older revision		Revision as of 15:36, 14 August 2022
Line 126:		Line 126:
	Intermittent fasting (IF) has attained popular interest in recent years for its various potential health benefits, including for treating disease and extending lifespan.<ref>Lee, M. B., Hill, C. M., Bitto, A., & Kaeberlein, M. (2021). Antiaging diets: Separating fact from fiction. ''Science'', ''374''(6570), eabe7365.		Intermittent fasting (IF) has attained popular interest in recent years for its various potential health benefits, including for treating disease and extending lifespan.<ref>Lee, M. B., Hill, C. M., Bitto, A., & Kaeberlein, M. (2021). Antiaging diets: Separating fact from fiction. ''Science'', ''374''(6570), eabe7365.

	Chicago</ref><ref name=":10">Longo, V. D., Di Tano, M., Mattson, M. P., & Guidi, N. (2021). Intermittent and periodic fasting, longevity and disease. ''Nature aging'', ''1''(1), 47-59.</ref> Some preclinical evidence shows that certain IF regimens can prevent the onset of many age-related diseases. However, IF is not always associated with benefits in healthspan and may increase or decrease lifespan.<ref name=":10" /> It has been proposed that at least part of the lifespan extending effect of CR is related to fasting.<ref name=":10" /><ref>Pak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., ... & Lamming, D. W. (2021). Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice. ''Nature metabolism'', ''3''(10), 1327-1341.</ref> In rodent models, the evidence for IF preventing cancer development or growth is ambiguous, with studies showing no effect or potential harm with IF. More studies are required to better understand IF, both for preclinical and clinical research.<ref>Clifton, K. K., Ma, C. X., Fontana, L., & Peterson, L. L. (2021). Intermittent fasting in the prevention and treatment of cancer. ''CA: a cancer journal for clinicians'', ''71''(6), 527-546.</ref>		Chicago</ref><ref name=":10">Longo, V. D., Di Tano, M., Mattson, M. P., & Guidi, N. (2021). Intermittent and periodic fasting, longevity and disease. ''Nature aging'', ''1''(1), 47-59.</ref> Some preclinical evidence shows that certain IF regimens can prevent the onset of many age-related diseases. However, IF is not always associated with benefits in healthspan and may increase or decrease lifespan.<ref name=":10" /> It has been proposed that at least part of the lifespan extending effect of CR in humans is related to fasting, and in rodents fasting is required for a CR diet to protect from frailty and extend lifespan.<ref name=":10" /><ref>Pak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., ... & Lamming, D. W. (2021). Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice. ''Nature metabolism'', ''3''(10), 1327-1341.</ref> In rodent models, the evidence for IF preventing cancer development or growth is ambiguous, with studies showing no effect or potential harm with IF. More studies are required to better understand IF, both for preclinical and clinical research.<ref>Clifton, K. K., Ma, C. X., Fontana, L., & Peterson, L. L. (2021). Intermittent fasting in the prevention and treatment of cancer. ''CA: a cancer journal for clinicians'', ''71''(6), 527-546.</ref>

	A recent study in China randomized 139 obese adults to either calorie restriction alone or to calorie restriction with time-restricted eating (a 16-hour intermittent fast and a 8-hour period for eating).<ref>Liu, D., Huang, Y., Huang, C., Yang, S., Wei, X., & Zhang, P. et al. (2022). Calorie Restriction with or without Time-Restricted Eating in Weight Loss. ''New England Journal Of Medicine'', ''386''(16), 1495-1504. doi: 10.1056/nejmoa2114833</ref> After one year, both groups had lost 7-10% of body weight and showed healthier markers for blood sugar, blood fat levels and insulin sensitivity. Importantly, there was no statistically significant difference between both groups, suggesting calorie restriction is responsible for the health-associated benefits and that intermittent fasting has no added benefits to CR diets.		A recent study in China randomized 139 obese adults to either calorie restriction alone or to calorie restriction with time-restricted eating (a 16-hour intermittent fast and a 8-hour period for eating).<ref>Liu, D., Huang, Y., Huang, C., Yang, S., Wei, X., & Zhang, P. et al. (2022). Calorie Restriction with or without Time-Restricted Eating in Weight Loss. ''New England Journal Of Medicine'', ''386''(16), 1495-1504. doi: 10.1056/nejmoa2114833</ref> After one year, both groups had lost 7-10% of body weight and showed healthier markers for blood sugar, blood fat levels and insulin sensitivity. Importantly, there was no statistically significant difference between both groups, suggesting calorie restriction is responsible for the health-associated benefits and that intermittent fasting has no added benefits to CR diets.

Andrea: /* Added links to new articles on PR and IF */

2022-08-11T11:48:39Z

Added links to new articles on PR and IF

← Older revision		Revision as of 11:48, 11 August 2022
Line 122:		Line 122:

	====== CR and Intermittent Fasting ======		====== CR and Intermittent Fasting ======
			''See the full article on [[fasting]].''

	Intermittent fasting (IF) has attained popular interest in recent years for its various potential health benefits, including for treating disease and extending lifespan.<ref>Lee, M. B., Hill, C. M., Bitto, A., & Kaeberlein, M. (2021). Antiaging diets: Separating fact from fiction. ''Science'', ''374''(6570), eabe7365.		Intermittent fasting (IF) has attained popular interest in recent years for its various potential health benefits, including for treating disease and extending lifespan.<ref>Lee, M. B., Hill, C. M., Bitto, A., & Kaeberlein, M. (2021). Antiaging diets: Separating fact from fiction. ''Science'', ''374''(6570), eabe7365.

Line 135:		Line 137:

	===== 7. Is diet composition important in CR? =====		===== 7. Is diet composition important in CR? =====
			''See the full article on [[protein restriction]].''

	Diet composition in CR is likely to be important. As mentioned previously, there is a general agreement that CR should reduce the total amount of calories ingested whilst avoiding malnutrition (ie. without reducing protein or macronutrient intake), in order to maximise health benefits.<ref name=":19" /><ref name=":20" /> In fact, an exhaustive review of literature suggested that most commonly adopted CR protocols led to malnutrition in rodents, which they argue might have added to the observed discrepancies in survival curves across CR interventions.<ref>Cerqueira, F., & Kowaltowski, A. (2010). Commonly adopted caloric restriction protocols often involve malnutrition. ''Ageing Research Reviews'', ''9''(4), 424-430. doi: 10.1016/j.arr.2010.05.002</ref>		Diet composition in CR is likely to be important. As mentioned previously, there is a general agreement that CR should reduce the total amount of calories ingested whilst avoiding malnutrition (ie. without reducing protein or macronutrient intake), in order to maximise health benefits.<ref name=":19" /><ref name=":20" /> In fact, an exhaustive review of literature suggested that most commonly adopted CR protocols led to malnutrition in rodents, which they argue might have added to the observed discrepancies in survival curves across CR interventions.<ref>Cerqueira, F., & Kowaltowski, A. (2010). Commonly adopted caloric restriction protocols often involve malnutrition. ''Ageing Research Reviews'', ''9''(4), 424-430. doi: 10.1016/j.arr.2010.05.002</ref>

	Some scientists have proposed that protein restriction (PR) in particular is responsible for the benefits observed in CR.<ref>Simpson, S., & Raubenheimer, D. (2007). Caloric Restriction and Aging Revisited: The Need for a Geometric Analysis of the Nutritional Bases of Aging. ''The Journals Of Gerontology Series A: Biological Sciences And Medical Sciences'', ''62''(7), 707-713. doi: 10.1093/gerona/62.7.707</ref><ref>Raubenheimer, D., Simpson, S., & Tait, A. (2012). Match and mismatch: conservation physiology, nutritional ecology and the timescales of biological adaptation. ''Philosophical Transactions Of The Royal Society B: Biological Sciences'', ''367''(1596), 1628-1646. doi: 10.1098/rstb.2012.0007</ref> However, more recent studies reviewing all published data since the early 1930s until 2016 concluded that lifespan extension in rodents is due to CR alone and not due to a reduction of protein or any other macronutrients.<ref>Speakman, J., Mitchell, S., & Mazidi, M. (2016). Calories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone. ''Experimental Gerontology'', ''86'', 28-38. doi: 10.1016/j.exger.2016.03.011</ref><ref>Pamplona, R., & Barja, G. (2006). Mitochondrial oxidative stress, aging and caloric restriction: The protein and methionine connection. ''Biochimica Et Biophysica Acta (BBA) - Bioenergetics'', ''1757''(5-6), 496-508. doi: 10.1016/j.bbabio.2006.01.009</ref>		Some scientists have proposed that [[protein restriction]] (PR) in particular is responsible for the benefits observed in CR.<ref>Simpson, S., & Raubenheimer, D. (2007). Caloric Restriction and Aging Revisited: The Need for a Geometric Analysis of the Nutritional Bases of Aging. ''The Journals Of Gerontology Series A: Biological Sciences And Medical Sciences'', ''62''(7), 707-713. doi: 10.1093/gerona/62.7.707</ref><ref>Raubenheimer, D., Simpson, S., & Tait, A. (2012). Match and mismatch: conservation physiology, nutritional ecology and the timescales of biological adaptation. ''Philosophical Transactions Of The Royal Society B: Biological Sciences'', ''367''(1596), 1628-1646. doi: 10.1098/rstb.2012.0007</ref> However, more recent studies reviewing all published data since the early 1930s until 2016 concluded that lifespan extension in rodents is due to CR alone and not due to a reduction of protein or any other macronutrients.<ref>Speakman, J., Mitchell, S., & Mazidi, M. (2016). Calories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone. ''Experimental Gerontology'', ''86'', 28-38. doi: 10.1016/j.exger.2016.03.011</ref><ref>Pamplona, R., & Barja, G. (2006). Mitochondrial oxidative stress, aging and caloric restriction: The protein and methionine connection. ''Biochimica Et Biophysica Acta (BBA) - Bioenergetics'', ''1757''(5-6), 496-508. doi: 10.1016/j.bbabio.2006.01.009</ref>

	== Controversies of calorie restriction research ==		== Controversies of calorie restriction research ==

Andrea: /* Finished adding final edits to article */

2022-07-23T19:49:44Z

Finished adding final edits to article

Show changes

Andrea: /* Humans */

2022-07-23T16:07:39Z

Humans

← Older revision		Revision as of 16:07, 23 July 2022
Line 54:		Line 54:
	'''The population of Okinawa'''		'''The population of Okinawa'''

	Studies into certain populations known for their exceptional longevity, such as in Okinawa - a small island of Japan - have provided some insights into potential lifestyle determinants of longevity. Okinawans have long been recognized as one of the ~~most long~~-lived populations on the planet, and this is typically attributed to their diet (fish and vegetables). However, more recently, some attention in the scientific community has deviated from the contents of Okinawan’s diets and focused, instead, on their caloric deficits. Six generations of Okinawans aged 65+ were studied; their diet composition, energy intake and expenditure, and survival patterns were analyzed, among many other factors. The results lent support to the wide-ranging health benefits of caloric restriction in humans. Some researchers have speculated that the introduction of Westernized diets may in part explain recent decreases in Okinawan population lifespan.<ref name=":0" />		Studies into certain populations known for their exceptional longevity, such as in Okinawa - a small island of Japan - have provided some insights into potential lifestyle determinants of longevity. Okinawans have long been recognized as one of the longest-lived populations on the planet, and this is typically attributed to their diet (fish and vegetables). However, more recently, some attention in the scientific community has deviated from the contents of Okinawan’s diets and focused, instead, on their caloric deficits. Six generations of Okinawans aged 65+ were studied; their diet composition, energy intake and expenditure, and survival patterns were analyzed, among many other factors. The results lent support to the wide-ranging health benefits of caloric restriction in humans. Some researchers have speculated that the introduction of Westernized diets may in part explain recent decreases in Okinawan population lifespan.<ref name=":0" />

	'''Biosphere-II'''		'''Biosphere-II'''