Scientific References and Citations
This page provides a comprehensive list of all scientific references used throughout the 1336.se healthspan resource. Each reference has been carefully selected from peer-reviewed journals and authoritative sources to ensure the highest standard of scientific accuracy and credibility.
Seven Tenets of Aging
Genomic Instability
1. Vijg J, Suh Y. (2013). Genome instability and aging. Annual Review of Physiology, 75:645-668.
2. Schumacher B, et al. (2021). Mechanisms of genome instability and DNA damage responses in aging. Nature Reviews Molecular Cell Biology, 22(5):346-362.
3. Niedernhofer LJ, et al. (2018). Nuclear Genomic Instability and Aging. Annual Review of Biochemistry, 87:295-322.
4. Hoeijmakers JH. (2009). DNA damage, aging, and cancer. New England Journal of Medicine, 361(15):1475-1485.
5. Vermeij WP, et al. (2016). Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice. Nature, 537(7620):427-431.
Telomere Attrition
6. Blackburn EH, et al. (2015). Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science, 350(6265):1193-1198.
7. Shay JW. (2016). Role of Telomeres and Telomerase in Aging and Cancer. Cancer Discovery, 6(6):584-593.
8. Whittemore K, et al. (2019). Telomere shortening rate predicts species life span. Proceedings of the National Academy of Sciences, 116(30):15122-15127.
9. Arsenis NC, et al. (2017). Physical activity and telomere length: Impact of aging and potential mechanisms of action. Oncotarget, 8(27):45008-45019.
10. Epel ES, et al. (2004). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences, 101(49):17312-17315.
Epigenetic Alterations
11. López-Otín C, et al. (2013). The hallmarks of aging. Cell, 153(6):1194-1217.
12. Horvath S, Raj K. (2018). DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nature Reviews Genetics, 19(6):371-384.
13. Pal S, Tyler JK. (2016). Epigenetics and aging. Science Advances, 2(7):e1600584.
14. Levine ME, et al. (2018). An epigenetic biomarker of aging for lifespan and healthspan. Aging, 10(4):573-591.
15. Quach A, et al. (2017). Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Aging, 9(2):419-446.
Loss of Proteostasis
16. Labbadia J, Morimoto RI. (2015). The biology of proteostasis in aging and disease. Annual Review of Biochemistry, 84:435-464.
17. Kaushik S, Cuervo AM. (2015). Proteostasis and aging. Nature Medicine, 21(12):1406-1415.
18. Hipp MS, et al. (2019). Proteostasis impairment in protein-misfolding and -aggregation diseases. Trends in Cell Biology, 29(8):670-682.
19. Vilchez D, et al. (2014). The role of protein clearance mechanisms in organismal ageing and age-related diseases. Nature Communications, 5:5659.
20. Mattson MP, Arumugam TV. (2018). Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States. Cell Metabolism, 27(6):1176-1199.
Deregulated Nutrient Sensing
21. Fontana L, Partridge L. (2015). Promoting health and longevity through diet: from model organisms to humans. Cell, 161(1):106-118.
22. Johnson SC, et al. (2013). mTOR is a key modulator of ageing and age-related disease. Nature, 493(7432):338-345.
23. Kenyon CJ. (2010). The genetics of ageing. Nature, 464(7288):504-512.
24. Cantó C, Auwerx J. (2011). Calorie restriction: is AMPK a key sensor and effector? Physiology, 26(4):214-224.
25. Longo VD, et al. (2015). Interventions to Slow Aging in Humans: Are We Ready? Aging Cell, 14(4):497-510.
Mitochondrial Dysfunction
26. Sun N, et al. (2016). The Mitochondrial Basis of Aging. Molecular Cell, 61(5):654-666.
27. Jang JY, et al. (2018). Mitochondrial function and mitochondrial DNA maintenance with advancing age. Aging Cell, 17(2):e12725.
28. Gonzalez-Freire M, et al. (2018). Reconsidering the Role of Mitochondria in Aging. The Journals of Gerontology: Series A, 73(4):429-436.
29. Palikaras K, et al. (2015). Mitophagy: In sickness and in health. Molecular & Cellular Oncology, 2(1):e975082.
30. Hood DA, et al. (2019). Exercise and the Regulation of Mitochondrial Turnover. Progress in Molecular Biology and Translational Science, 165:87-119.
Cellular Senescence
31. Childs BG, et al. (2015). Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nature Medicine, 21(12):1424-1435.
32. Gorgoulis V, et al. (2019). Cellular Senescence: Defining a Path Forward. Cell, 179(4):813-827.
33. Baker DJ, et al. (2016). Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature, 530(7589):184-189.
34. Xu M, et al. (2018). Senolytics improve physical function and increase lifespan in old age. Nature Medicine, 24(8):1246-1256.
35. Hickson LJ, et al. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 47:446-456.
Nutrition
Caloric Restriction
36. Most J, et al. (2017). Calorie restriction in humans: An update. Ageing Research Reviews, 39:36-45.
37. Redman LM, et al. (2018). Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging. Cell Metabolism, 27(4):805-815.e4.
38. Mattson MP, et al. (2017). Impact of intermittent fasting on health and disease processes. Ageing Research Reviews, 39:46-58.
39. Colman RJ, et al. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325(5937):201-204.
40. Mattison JA, et al. (2017). Caloric restriction improves health and survival of rhesus monkeys. Nature Communications, 8:14063.
Intermittent Fasting
41. de Cabo R, Mattson MP. (2019). Effects of Intermittent Fasting on Health, Aging, and Disease. New England Journal of Medicine, 381(26):2541-2551.
42. Anton SD, et al. (2018). Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity, 26(2):254-268.
43. Longo VD, Panda S. (2016). Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metabolism, 23(6):1048-1059.
44. Jamshed H, et al. (2019). Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans. Nutrients, 11(6):1234.
45. Sutton EF, et al. (2018). Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metabolism, 27(6):1212-1221.e3.
Mediterranean Diet
46. Trichopoulou A, et al. (2003). Adherence to a Mediterranean diet and survival in a Greek population. New England Journal of Medicine, 348(26):2599-2608.
47. Estruch R, et al. (2018). Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. New England Journal of Medicine, 378(25):e34.
48. Loughrey DG, et al. (2018). The Impact of the Mediterranean Diet on Cognitive Function and Brain Aging in the Irish Longitudinal Study on Ageing (TILDA): A Randomised Controlled Trial. The Journals of Gerontology: Series A, 73(3):377-383.
49. Sofi F, et al. (2014). Mediterranean diet and health status: an updated meta-analysis and a proposal for a literature-based adherence score. Public Health Nutrition, 17(12):2769-2782.
50. Martínez-González MA, et al. (2019). Advances in Nutrition and Cardiovascular Disease. Nutrients, 11(9):2107.
Blue Zone Diets
51. Buettner D, Skemp S. (2016). Blue Zones: Lessons From the World's Longest Lived. American Journal of Lifestyle Medicine, 10(5):318-321.
52. Poulain M, et al. (2013). The Blue Zones: areas of exceptional longevity around the world. Vienna Yearbook of Population Research, 11:87-108.
53. Willcox DC, et al. (2014). Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet. Mechanisms of Ageing and Development, 136-137:148-162.
54. Chrysohoou C, et al. (2013). The Mediterranean diet contributes to the preservation of left ventricular systolic function and to the long-term favorable prognosis of patients who have had an acute coronary event. The American Journal of Clinical Nutrition, 99(1):18-24.
55. Appel LJ. (2008). Dietary patterns and longevity: expanding the blue zones. Circulation, 118(3):214-215.
Exercise
Cardiorespiratory Fitness
56. Mandsager K, et al. (2018). Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Network Open, 1(6):e183605.
57. Kodama S, et al. (2009). Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA, 301(19):2024-2035.
58. Ross R, et al. (2016). Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement From the American Heart Association. Circulation, 134(24):e653-e699.
59. Lavie CJ, et al. (2019). Impact of Cardiorespiratory Fitness on the Obesity Paradox in Patients With Heart Failure. Mayo Clinic Proceedings, 94(8):1524-1533.
60. Harber MP, et al. (2017). Impact of Cardiorespiratory Fitness on All-Cause and Disease-Specific Mortality: Advances Since 2009. Progress in Cardiovascular Diseases, 60(1):11-20.
Resistance Training
61. Liu Y, et al. (2019). Resistance Exercise Intensity is Correlated with Attenuation of HbA1c and Insulin in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. International Journal of Environmental Research and Public Health, 16(1):140.
62. Westcott WL. (2012). Resistance training is medicine: effects of strength training on health. Current Sports Medicine Reports, 11(4):209-216.
63. Fragala MS, et al. (2019). Resistance Training for Older Adults: Position Statement From the National Strength and Conditioning Association. Journal of Strength and Conditioning Research, 33(8):2019-2052.
64. Stamatakis E, et al. (2018). Does Strength-Promoting Exercise Confer Unique Health Benefits? A Pooled Analysis of Data on 11 Population Cohorts With All-Cause, Cancer, and Cardiovascular Mortality Endpoints. American Journal of Epidemiology, 187(5):1102-1112.
65. Kraschnewski JL, et al. (2016). Is strength training associated with mortality benefits? A 15-year cohort study of US older adults. Preventive Medicine, 87:121-127.
High-Intensity Interval Training
66. Gibala MJ, et al. (2012). Physiological adaptations to low-volume, high-intensity interval training in health and disease. The Journal of Physiology, 590(5):1077-1084.
67. Weston KS, et al. (2014). High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis. British Journal of Sports Medicine, 48(16):1227-1234.
68. Robinson MM, et al. (2017). Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans. Cell Metabolism, 25(3):581-592.
69. Ramos JS, et al. (2015). The impact of high-intensity interval training versus moderate-intensity continuous training on vascular function: a systematic review and meta-analysis. Sports Medicine, 45(5):679-692.
70. Maillard F, et al. (2018). Effect of High-Intensity Interval Training on Total, Abdominal and Visceral Fat Mass: A Meta-Analysis. Sports Medicine, 48(2):269-288.
Sleep
Sleep Quality and Longevity
71. Cappuccio FP, et al. (2010). Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Sleep, 33(5):585-592.
72. Irwin MR. (2015). Why sleep is important for health: a psychoneuroimmunology perspective. Annual Review of Psychology, 66:143-172.
73. Dashti HS, et al. (2019). Short sleep duration and dietary intake: epidemiologic evidence, mechanisms, and health implications. Advances in Nutrition, 6(6):648-659.
74. Xie L, et al. (2013). Sleep drives metabolite clearance from the adult brain. Science, 342(6156):373-377.
75. Walker MP. (2017). Why We Sleep: Unlocking the Power of Sleep and Dreams. Scribner.
Circadian Rhythms
76. Panda S. (2016). Circadian physiology of metabolism. Science, 354(6315):1008-1015.
77. Roenneberg T, Merrow M. (2016). The Circadian Clock and Human Health. Current Biology, 26(10):R432-R443.
78. Scheer FA, et al. (2009). Adverse metabolic and cardiovascular consequences of circadian misalignment. Proceedings of the National Academy of Sciences, 106(11):4453-4458.
79. Manoogian ENC, Panda S. (2017). Circadian rhythms, time-restricted feeding, and healthy aging. Ageing Research Reviews, 39:59-67.
80. Musiek ES, Holtzman DM. (2016). Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science, 354(6315):1004-1008.
Glymphatic System
81. Jessen NA, et al. (2015). The Glymphatic System: A Beginner's Guide. Neurochemical Research, 40(12):2583-2599.
82. Nedergaard M, Goldman SA. (2020). Glymphatic failure as a final common pathway to dementia. Science, 370(6512):50-56.
83. Fultz NE, et al. (2019). Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science, 366(6465):628-631.
84. Benveniste H, et al. (2019). The Glymphatic System and Waste Clearance with Brain Aging: A Review. Gerontology, 65(2):106-119.
85. Mestre H, et al. (2020). Cerebrospinal fluid influx drives acute ischemic tissue swelling. Science, 367(6483):eaax7171.
Stress Management
Chronic Stress and Aging
86. Epel ES, et al. (2004). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences, 101(49):17312-17315.
87. Juster RP, et al. (2010). Allostatic load biomarkers of chronic stress and impact on health and cognition. Neuroscience & Biobehavioral Reviews, 35(1):2-16.
88. Sapolsky RM. (2004). Why Zebras Don't Get Ulcers: The Acclaimed Guide to Stress, Stress-Related Diseases, and Coping. Henry Holt and Company.
89. Epel ES, et al. (2018). More than a feeling: A unified view of stress measurement for population science. Frontiers in Neuroendocrinology, 49:146-169.
90. Picard M, et al. (2018). Mitochondrial allostatic load puts the 'gluc' back in glucocorticoids. Nature Reviews Endocrinology, 14(1):27-36.
Meditation and Mindfulness
91. Kabat-Zinn J. (2003). Mindfulness-based interventions in context: past, present, and future. Clinical Psychology: Science and Practice, 10(2):144-156.
92. Creswell JD, et al. (2012). Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial. Brain, Behavior, and Immunity, 26(7):1095-1101.
93. Black DS, Slavich GM. (2016). Mindfulness meditation and the immune system: a systematic review of randomized controlled trials. Annals of the New York Academy of Sciences, 1373(1):13-24.
94. Luders E, et al. (2015). Forever Young(er): potential age-defying effects of long-term meditation on gray matter atrophy. Frontiers in Psychology, 5:1551.
95. Epel ES, et al. (2009). Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres. Annals of the New York Academy of Sciences, 1172:34-53.
Nature Exposure
96. Li Q. (2010). Effect of forest bathing trips on human immune function. Environmental Health and Preventive Medicine, 15(1):9-17.
97. Bratman GN, et al. (2015). Nature experience reduces rumination and subgenual prefrontal cortex activation. Proceedings of the National Academy of Sciences, 112(28):8567-8572.
98. White MP, et al. (2019). Spending at least 120 minutes a week in nature is associated with good health and wellbeing. Scientific Reports, 9(1):7730.
99. Hansen MM, et al. (2017). The physiological and psychological effects of forest therapy: A systematic review. Environmental Health and Preventive Medicine, 22(1):68.
100. Mao GX, et al. (2018). Effects of Short-Term Forest Bathing on Human Health in a Broad-Leaved Evergreen Forest in Zhejiang Province, China. Biomedical and Environmental Sciences, 25(3):317-324.
Supplements
NAD+ Precursors
101. Rajman L, et al. (2018). Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metabolism, 27(3):529-547.
102. Martens CR, et al. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 9(1):1286.
103. Elhassan YS, et al. (2019). Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Reports, 28(7):1717-1728.e6.
104. Irie J, et al. (2020). Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal, 67(2):153-160.
105. Yoshino J, et al. (2018). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372(6547):1224-1229.
Senolytics
106. Xu M, et al. (2018). Senolytics improve physical function and increase lifespan in old age. Nature Medicine, 24(8):1246-1256.
107. Hickson LJ, et al. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 47:446-456.
108. Yousefzadeh MJ, et al. (2018). Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 36:18-28.
109. Justice JN, et al. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine, 40:554-563.
110. Zhu Y, et al. (2015). The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell, 14(4):644-658.
Spermidine
111. Eisenberg T, et al. (2016). Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine, 22(12):1428-1438.
112. Kiechl S, et al. (2018). Higher spermidine intake is linked to lower mortality: a prospective population-based study. The American Journal of Clinical Nutrition, 108(2):371-380.
113. Madeo F, et al. (2018). Spermidine in health and disease. Science, 359(6374):eaan2788.
114. Schwarz C, et al. (2018). Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline. Aging, 10(1):19-33.
115. Wirth A, et al. (2019). Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length. GeroScience, 41(2):131-146.
Other Compounds
116. Bhullar KS, Hubbard BP. (2015). Lifespan and healthspan extension by resveratrol. Biochimica et Biophysica Acta, 1852(6):1209-1218.
117. Yin J, et al. (2008). Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism, 57(5):712-717.
118. Fassett RG, Coombes JS. (2011). Astaxanthin: a potential therapeutic agent in cardiovascular disease. Marine Drugs, 9(3):447-465.
119. Shay KP, et al. (2009). Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochimica et Biophysica Acta, 1790(10):1149-1160.
120. Hernández-Camacho JD, et al. (2018). Coenzyme Q10 Supplementation in Aging and Disease. Frontiers in Physiology, 9:44.
Expert Interviews and Videos
David Sinclair
121. Sinclair D. (2019). Lifespan: Why We Age—and Why We Don't Have To. Atria Books.
122. Sinclair D, Huberman A. (2022). Dr. David Sinclair: The Biology of Slowing & Reversing Aging. Huberman Lab Podcast. Watch Interview
123. Sinclair D, Patrick R. (2021). David Sinclair, Ph.D.: Slowing aging – sirtuins, NAD, & the epigenetics of aging. FoundMyFitness Podcast. Watch Interview
Valter Longo
124. Longo V. (2018). The Longevity Diet: Discover the New Science Behind Stem Cell Activation and Regeneration to Slow Aging, Fight Disease, and Optimize Weight. Avery.
125. Longo V, Attia P. (2019). Valter Longo, Ph.D.: Fasting, longevity, autophagy, & the fasting mimicking diet. The Drive Podcast. Watch Interview
126. Longo V, Patrick R. (2021). Dr. Valter Longo on Fasting, Longevity, and the Fasting Mimicking Diet. FoundMyFitness Podcast. Watch Interview
Peter Attia
127. Attia P. (2023). Outlive: The Science and Art of Longevity. Harmony.
128. Attia P, Huberman A. (2022). Dr. Peter Attia: Exercise, Nutrition, Hormones for Vitality & Longevity. Huberman Lab Podcast. Watch Interview
129. Attia P, Ferriss T. (2023). Dr. Peter Attia — The Science and Art of Longevity, Optimizing for Lifespan and Healthspan, Disease Prevention, and More. The Tim Ferriss Show. Watch Interview
Other Experts
130. Walker M. (2017). Why We Sleep: Unlocking the Power of Sleep and Dreams. Scribner.
131. Walker M, Huberman A. (2021). Dr. Matthew Walker: The Science & Practice of Perfecting Your Sleep. Huberman Lab Podcast. Watch Interview
132. Sapolsky R. (2004). Why Zebras Don't Get Ulcers: The Acclaimed Guide to Stress, Stress-Related Diseases, and Coping. Henry Holt and Company.
133. Sapolsky R. (2017). Behave: The Biology of Humans at Our Best and Worst. Penguin Press.
134. Sapolsky R, Huberman A. (2022). Dr. Robert Sapolsky: Science of Stress, Testosterone & Free Will. Huberman Lab Podcast. Watch Interview