INDEX

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Note: Page numbers in italics indicate figures and tables.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

A

  • accidental deaths, 226–227, 227, 381–382

  • ACHIEVE (Aging and Cognitive Health Evaluation in Elders), 203

  • adoptive cell therapy (adoptive cell transfer; ACT), 163–164

  • aducanumab, 183

  • aerobic fitness. See cardiorespiratory fitness

  • aging process, 43–45, 71, 143–144, 143, 363–364

  • alanine aminotransferase (ALT), 91–92, 91n

  • alcohol

    • Alzheimer’s disease and, 201, 321

    • anesthesia considerations, 89

    • centenarians and, 59–60, 61

    • liver disease and, 89–90

    • recommendations, 320–321

    • research on, 302

    • sleep and, 321, 371–372, 374

  • Ali, Muhammad, 41–44, 72, 216

  • Allingham, Henry, 59

  • Allison, David, 300–301

  • Allison, James, 160–161, 160n

  • Alzheimer, Alois, 181, 182, 185

  • Alzheimer’s disease

    • amyloid hypothesis, 182–185

    • amyloid hypothesis alternatives, 194–197

    • APOE gene variants (e2, e3, e4), 67–69, 178–179, 180, 189, 196, 197–199

    • background, 83, 102, 180–186

    • conclusion, 204–205

    • early detection strategy, 178–179, 180

    • Medicine 2.0 vs. Medicine 3.0 approaches, 188, 190

  • prevention strategy, 186–193, 199–204, 225, 321, 326, 363

  • risk factors, 17, 71–72, 109, 188–189, 196

  • treatments targeting amyloid, 183–184

  • Alzheimer’s Treatment, Alzheimer’s Prevention (Isaacson), 187

  • Ambien, 364, 365, 366

  • AMP-activated protein kinase (AMPK), 82

  • amyloid-beta, 182–185, 195–196, 362–363

  • amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease), 83, 179

  • Andrews, Peter, 104–105

  • APOE gene variants (e2, e3, e4), 67–69, 178–179, 180, 189, 196, 197–199

  • apolipoprotein A (apoA), 117, 120

  • apolipoprotein B (apoB), 117, 117n, 120, 121, 133–134, 137

  • apolipoprotein B (apoB) test, 126–127, 130–131, 132

  • apolipoprotein E (APOE), 67–68, 197–198

  • Aretaeus of Cappadocia, 102

  • arterial plaque, 122, 124–125

  • Ashkenazi Jewish centenarians, 61

  • ashwagandha, 366

  • atherosclerotic cardiovascular disease (ASCVD). See cardiovascular disease

  • atherosclerotic plaque, 122, 124–125

  • Atlas of Atherosclerosis Progression and Regression (Stary), 119

  • automobile accident analogy, 212–213

  • autophagy, 82–83, 341

B

  • Bacon, Francis, 27

  • balloon analogy, 101, 108

  • “Barry Get-Up” fitness assessment, 290

  • Barzilai, Nir, 61, 64, 87

  • bathtub analogy, 98

  • B-cell lymphoma, 160

  • bempedoic acid (Nexletol), 138

  • Betts, James, 344

  • Blessed, Garry, 181, 184, 194

  • blood pressure. See high blood pressure

  • blood test for cancer (liquid biopsy), 145, 172–175, 172n

  • Boorstin, Daniel J., 177

  • borderline personality disorder, 400

  • Bowers, Mildred, 60

  • Bradford Hill, Austin, 222n, 298

  • Bradford Hill criteria, 298–299, 298n

  • brain-derived neurotrophic factor (BDNF), 225

  • brain glucose metabolism, 194–196

  • breast cancer, 33n, 146–147, 152, 153, 167, 167n, 168, 303, 303n

  • breathing, 272–277, 276n

  • Bridge to Recovery, 377–380, 383–388, 397

  • Brooks, David, 394

  • Brooks, George, 238, 241

  • Buddha, 403

  • Burns, Ken, 158

C

  • caffeine, 372–373

  • calcium score, 113–114, 124–126, 124n, 128, 135–136, 136n

  • Calment, Jeanne, 59–60, 61

  • calorie restriction (CR), 79–83, 152–153, 309, 310, 311–316

  • cancer, 140–176. See also specific types of cancer

    • background, 102, 140–142

    • centenarians and, 63

    • conclusion, 175–176

    • demographics, 142–144, 143

    • genetic mutations and, 145–147, 150–151

    • meat and, 299–300

    • Medicine 2.0 vs. Medicine 3.0 approaches, 167, 176

    • risk factors, 53–54, 72, 107–108, 109

    • strategy: early detection (background), 145, 165–167

    • strategy: early detection (future directions), 86, 172–175

    • strategy: early detection strategy (trade-offs), 167–172, 172n

    • strategy: overview, 144–145

    • strategy: treatment (dietary interventions), 154–158

    • strategy: treatment (immunotherapy), 158–165, 160n

    • strategy: treatment (overview), 145, 147–149

  • The Cancer Genome Atlas, 146–147

  • Cantley, Lew, 151, 152–153, 154–155, 156

  • car accident analogy, 212–213

  • carbohydrates, 318, 322–330, 347

  • cardiorespiratory fitness

    • background, 216–218

    • benefits of, 201–202, 219–223, 222n, 222, 224n, 225

    • maximum aerobic output, 220–221, 223, 244–252, 246, 250–251n, 250

    • overview, 236

    • power of, 287–290

    • preparation overview, 236

    • sleep and, 354–355, 355n

    • zone 2 training, 237–244

  • cardiovascular disease, 111–139

    • background, 15–16, 111–115, 209

    • centenarians and, 63

    • cholesterol and, 115–119

    • demographics, 112–113, 142–143

    • excess fats and, 98, 99

    • lipid-lowering medications for, 129–130, 130n, 133–134, 136–139

    • Lp(a) and, 127–130

    • Medicine 2.0 vs. Medicine 3.0 approaches, 29, 130, 137

    • progression of, 119–125, 134–137

    • risk factors, 71–72, 109, 125–127, 196

    • risk reduction, 130–139

    • sleep and, 357, 358–359

  • CAR-T (chimeric antigen receptor T cells), 159–160

  • Case, Anne, 382

  • causation

    • in clinical trials, 302–306

    • in epidemiology, 53, 53n, 297–302

  • CCGA (Circulating Cell-free Genome Atlas), 174–175

  • Centenarian Decathlon

    • background, 229–230

    • maximum aerobic output, 220–221, 223, 244–252, 246, 250–251n, 250

    • overview and questions to ask, 231–234

    • preparation overview, 235–237

    • strength foundation training, 255–262, 263–290. See also stability training

    • zone 2 training, 237–244

  • centenarians

    • genetics of, 62, 66–70

    • Medicine 2.0 vs. Medicine 3.0 approaches, 65–66

    • phase shift of, 63–66, 71–72

    • research on, 51–52, 60–62

    • “secrets” to living longer, 59–60, 70–72

  • Centers for Disease Control (CDC), 93

  • central adiposity, 94

  • cerebrovascular disease (stroke), 63, 112–113, 195–196, 224

  • cervical cancer, 167, 171

  • CGM (continuous glucose monitoring), 31, 323–330, 323n, 324n

  • Chandel, Navdeep, 74–75

  • checkpoint inhibitors, 160–162, 160n, 163

  • chemotherapy, 148–149

  • chimeric antigen receptor T cells (CAR-T), 159–160

  • cholesterol, 16, 68, 71–72, 115–119, 197–198

  • cholesterol efflux, 123

  • chronotypes, 368–369, 368n

  • Circulating Cell-free Genome Atlas (CCGA), 174–175

  • cirrhosis, 92–93

  • clinical trials, 297, 302–306

  • Coelho, Paulo, 408

  • cognitive behavioral therapy, 400

  • Cognitive Behavioral Therapy for Insomnia (CBT-I), 376

  • Coley, William, 158–159

  • colon cancer, 153, 161–162, 166, 166n, 169–171, 169–171nn

  • The Comfort Crisis (Easter), 256–257

  • concentric loading, 257, 260

  • Conti, Paul, 380, 388, 395–396, 397

  • continuous glucose monitoring (CGM), 31, 323–330, 323n, 324n

  • Corby, Patricia, 203

  • Cornaro, Alvise, 79–80

  • Cornaro, Luigi, 312

  • correlation

    • in clinical trials, 302–306

    • in epidemiology, 297–302

  • COVID-19, 28, 43–44, 242n, 396–397, 404

  • Crick, Francis, 150

  • crime scene analogy, 119–121, 124

  • CT angiogram, 124, 124n, 135–136, 136n

  • cytokines, 86, 98, 225

D

  • Dayspring, Tom, 114, 128, 344–346

  • Dayvigo (lemborexant), 365–366

  • DBT (dialectical behavior therapy), 400–407

  • DeAngelo, James, 140–141, 164

  • Deaton, Angus, 382

  • decathlon. See Centenarian Decathlon

  • de la Torre, Jack, 194–195

  • dementia. See neurodegenerative diseases

  • dementia with Lewy bodies, 179

  • dental health, 203

  • depression, 196, 203, 390–392

  • Deter, Auguste, 181, 182, 185

  • DHA, 200, 336–337, 340

  • Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), 388

  • dialectical behavior therapy (DBT), 400–407

  • Diehn, Max, 172–173

  • dietary restrictions (DR), 309, 310, 317–320. See also specific diets

  • diffusion-weighted imaging MRI, 171–172

  • “Discourses on the Sober Life” (Cornaro), 80

  • distress tolerance, 401, 402, 404–405

  • DNS (dynamic neuromuscular stabilization), 270–271, 272, 275, 280n

  • Dog Aging Project, 85–86

  • Down syndrome, 182

  • Dunning-Kruger curve, 293–294, 293

  • DWI MRI, 171–172

  • dynamic neuromuscular stabilization (DNS), 270–271, 272, 275, 280n

E

  • early-onset Alzheimer’s disease, 182, 185

  • Easter, Michael, 256–257

  • Easter Island (Rapa Nui), 73–76, 87n

  • eccentric loading, 257, 260–261

  • effectiveness tests, 304

  • efficacy tests, 304

  • eggs, 118

  • Elias, Ric, 410–411

  • emergency landing on Hudson River, 410–411

  • emotional health, 377–408

    • conclusion, 399–400, 407–408

    • COVID-19 and, 396–397, 404

    • importance of, 17, 380–383

    • inpatient treatment, 377–380, 383–388, 397–399, 400

    • as longevity tactic, 47

    • male depression, 390–392

    • medications, 399, 401

    • Medicine 2.0 vs. Medicine 3.0 approaches, 388–389

    • mental health comparison, 388–389

    • nutritional biochemistry and, 401

    • overview, 49, 50

    • tools for, 361–362, 392–396, 398–399, 400–407

    • trauma and, 384–388

  • The Emperor of All Maladies (Mukherjee), 155, 156, 158

  • endometrial cancer, 152, 153

  • endothelium, 119–123, 122, 128

  • endurance exercise. See cardiorespiratory fitness

  • English, Jeff, 386, 390

  • EPA, 336–337, 340

  • epidemiology, 53, 53n, 297–302

  • Epworth Sleepiness Scale, 368, 368n

  • esophageal cancer, 152, 153

  • ethyl eicosapentaenoic acid (Vascepa), 139

  • eulogy virtues, 394, 410

  • everolimus, 76, 84

  • evidence-based medicine, 50–51

  • evolution, 66–67, 103–106, 198, 353, 362n

  • exercise

    • background, 48, 216–218

    • benefits of, 17, 47, 48, 100, 201–202, 218–228, 222n, 222, 224n, 254–256

    • continuous glucose monitoring and, 329, 330

    • emotional health and, 401, 405–406

    • Medicine 2.0’s approach to, 219

    • power of, 287–290

    • sleep and, 354–355, 355n, 373, 374

    • training recommendations, 229–234. See also centenarian decathlon

    • types of, 237–262. See also cardiorespiratory fitness; strength training

  • Extra Life (Johnson), 28

  • ezetimibe (Zetia), 138, 138n

F

  • fasting, 156–157, 309, 310–311, 340–346

  • fasting glucose test, 31, 94, 101, 323

  • fats (dietary), 304–306, 318, 329–330, 335–336n, 335–340, 347

  • fat storage, 96–100, 104, 107n, 237, 238–239

  • “fatty streak,” 121–122, 122

  • Ferriss, Tim, 74–75

  • Feynman, Richard, 27, 291, 292

  • “First, do no harm,” 23–24, 23n, 88

  • Flaherty, Keith, 157

  • flossing, 203

  • foam cells, 121, 122, 123, 124

  • follicular lymphoma, 159–160

  • food frequency questionnaire, 299, 299n

  • food supply safety, 210n

  • Foreman, George, 41–43, 72

  • Four Horsemen. See cancer; heart disease; metabolic dysfunction and metabolic syndrome; neurodegenerative diseases

  • FOXO3 gene, 69–70

  • frailty, 253–255

  • Franklin, Rosalind, 150

  • fructose, 104–107, 210, 329

G

  • Galleri (Grail test), 174–175

  • Galpin, Andy, 252–253

  • Gandhi, Mahatma, 349

  • Gay, Nathan, 163

  • genetics. See also specific genes

    • Alzheimer’s disease and, 67–69

    • of cancer cells, 145–147, 150–151, 159n

    • fat-storage capacity, 98–99

    • of longevity, 62, 66–70, 123–124

    • of metabolic dysfunction, 199

  • gentamicin, 20–21

  • ghrelin, 358

  • glioblastoma, 147

  • glucose metabolism

    • APOE and, 68

    • in brain, 194–196

    • of cancer cells, 149–154, 156

    • carbohydrates and, 322–330

    • exercise and, 237, 238–239, 241–243

  • fructose comparison, 106–107, 106–107n

  • sleep and, 357–358

  • storage of glucose, 96–97

  • glycogen, 96–97

  • Gonzalez-Lima, Francisco, 192

  • Gordon, Robert J., 28

  • gout, 102, 104, 106

  • Grail test (Galleri), 174–175

  • grandiosity, 391

  • Griffin, John, 216–217, 218

  • grip strength, 201, 202, 256–257, 258–260

  • growth hormone, 364

H

  • Hamlet (Shakespeare), 403

  • Hanahan, Douglas, 149

  • Harper, Bob, 128–129

  • Hawthorne effect, 325–326, 330

  • HDL (“good”) cholesterol, 94, 116, 120, 123–124, 123n, 132–133

  • healthcare reimbursement system, 33–34

  • healthspan

    • of centenarians, 64–65

    • defined, 10–11

    • deterioration vectors, 45–47

    • Four Horsemen and. See cancer; heart disease; metabolic dysfunction and metabolic syndrome; neurodegenerative diseases

    • Marginal Decade vs. Bonus Decade, 36–40, 39, 65

    • Medicine 2.0 vs. Medicine 3.0 approaches, 33, 38–40, 39, 65

    • strategy for extension of, 41–47

    • tactics for expansion of, 47–50

  • Healthy Aging and Body Composition Study, 334

  • healthy user bias, 193, 301–302, 301n, 321

  • hearing loss, 203

  • heart attack. See heart disease

  • heart disease. See atherosclerotic cardiovascular disease

  • hemoglobin A1c (HbA1c) test, 13–14, 13n, 31, 108

  • high blood pressure

    • as Alzheimer’s disease risk factor, 196

    • as cardiovascular risk factor, 120–121, 126, 133

    • centenarians and, 63

    • metabolic dysfunction and, 94, 104, 106

    • sleep and, 357, 369n

  • high-density lipoproteins. See HDL (“good”) cholesterol

  • high-fructose corn syrup, 105n

  • hip-hinging movements, 258, 261–262, 268–271, 269, 285–287

  • Hippocrates, 23–24, 23n, 25–26, 79, 88

  • Hitchens, Christopher, 148–149

  • Hodgkin’s lymphoma, 143

  • Holiday, Ryan, 406

  • homocysteine, 108, 132, 132n, 204

  • Honjo, Tasuku, 161

  • Horner, Jack, 73

  • Horsemen. See cancer; heart disease; metabolic dysfunction and metabolic syndrome; neurodegenerative diseases

  • HRT (hormone replacement therapy), 32–33, 33n, 204, 254–255

  • Huntington’s disease, 179

  • hypertension. See high blood pressure

I

  • I Don’t Want to Talk About It (Real), 390

  • IGF-1 (insulin-like growth factor), 153–155

  • immunosuppression, 84–87

  • immunotherapy, 140–142, 149, 158–165, 160n

  • infectious (contagious) disease, 26–28, 28, 198

  • inflammation, 85–86, 98

  • injury prevention, 263–265. See also stability training

  • Inman, Thomas, 23n

  • insomnia, 363, 365–366, 373, 376

  • Insomnia Severity Index, 368, 368n

  • insulin, 97, 99, 108–109, 152–154, 156, 196–197, 340

  • insulin resistance

    • as Alzheimer’s disease risk factor, 196–197

    • as cancer risk factor, 154

    • as cardiovascular risk factor, 126

    • defined, 100–101

    • Medicine 2.0’s approach to, 109–110

    • metabolic dysfunction and, 98, 99, 100–102

    • prevention through exercise, 224

    • sleep and, 356–357, 358

    • type 2 diabetes cause, 109

  • intermittent fasting, 310–311

  • intersections-car accident analogy, 212–213

  • intra-abdominal pressure (IAP), 275–276

  • Ioannidis, John, 224, 224n, 300

  • ipilimumab (Yervoy), 161

  • Isaacson, Richard, 186–187, 191, 192

J

  • Johnson, Rick, 104–105

  • Johnson, Steven, 28

  • Joslin, Elliott, 102

  • Joyner, Mike, 221

K

  • Kaeberlein, Matt, 84, 85–86

  • Kennedy, John F., 20

  • ketogenic diet, 133, 155–156, 200–201, 292–293, 319–320, 339n

  • Keys, Ancel, 118

  • Keytruda, 162

  • kidney (renal) cancer, 152, 153, 159, 159n

  • King Lear (Shakespeare), 181

  • Klickstein, Lloyd, 84

  • Klotho (KL) gene, 180, 199

  • Knauss, Sarah, 61

  • Knight, Bobby, 395, 403–404

  • Koch, Robert, 26, 26n

  • Kochalka, Jim, 404

  • Krauss, Ron, 114

  • Kübler-Ross, Elisabeth, 23

L

  • lactate, 151, 151n, 240–242

  • LaLanne, Jack, 234

  • Layman, Don, 333–334

  • Lazar, Mitch, 99

  • LDL (“bad”) cholesterol

    • as cancer risk, 53–54

    • as cardiovascular risk factor, 116, 120–121, 137

    • levels of (LDL-C), 123–124, 123n, 126, 127, 131–132, 131n, 133n

    • liver and, 133n

    • Lp(a) and, 128

  • LDL receptors (LDLR), 133n, 134

  • Lee, Bruce, 209

  • leptin, 107n, 358

  • leukemia, 142, 143, 160

  • Lewis, Beth, 262, 268–270, 272–279, 281–284, 288–290

  • Lewy, Friedrich, 185

  • Lewy body dementia, 179, 185, 189

  • Libby, Peter, 131, 137–138

  • lifespan, 38–40, 39, 44–45, 65

  • Linehan, Marsha, 400

  • lipid-lowering medications, 128–129, 130n, 133–134, 136–139

  • lipid management, 133–134

  • lipoproteins, 68, 108, 116–117, 117n. See also HDL (“good”) cholesterol; LDL (“bad”) cholesterol

  • liquid biopsies, 145, 172–175, 172n

  • Lister, Joseph, 26, 26n, 27

  • liver

    • alcohol metabolism in, 321

    • cholesterol and, 116

    • fasting and, 340

    • glucose metabolism and, 96

    • LDL receptors and, 133n, 134

  • metabolic dysfunction and, 88–93, 98, 99, 107–108

  • regeneration potential of, 92

  • liver cancer, 147, 152, 153

  • longevity, 59–72. See also centenarians

    • author’s quest to understand, 14–19, 50, 73–75

    • defined, 9–11

    • from evidence-based to evidence-informed, 50–55

    • Four Horsemen and. See cancer; heart disease; metabolic dysfunction and metabolic syndrome; neurodegenerative diseases

    • Medicine 2.0 vs. Medicine 3.0 approaches, 11–14, 33–34, 47–51, 71

    • objective of, 36–40, 46–47

    • outlook on, 409–411

    • rapamycin and, 73–79, 77n, 83–87

    • rethinking, 17–19, 20–35. See also paradigm shift

    • slow deaths, 7–9

    • strategy for, 41–47, 50–55, 70–72

    • tactics for expansion of, 47–50, 209–215. See also emotional health; exercise; nutritional biochemistry; sleep; specific medications and supplements

  • Longo, Valter, 156–157

  • Lou Gehrig’s disease (ALS), 83, 179

  • low-density lipoproteins. See LDL (“bad”) cholesterol

  • Lp(a), 127–130, 130n, 131, 131n, 137

  • Lunesta, 365

  • lung cancer, 13, 147, 163, 171–172

  • lymphomas, 143, 159–160

  • Lynch syndrome, 161–162

M

  • macronutrients. See alcohol; carbohydrates; fats (dietary); protein

  • macrophages, 121, 122, 123

  • Mannick, Joan, 84

  • Marginal Decade, 37–40, 39, 65

  • maximum aerobic output, 220–221, 223, 244–252, 246, 250–251n, 250

  • MCI (mild cognitive impairment), 190, 363

  • McKinsey & Company, 22–23

  • Mediterranean diet, 200, 304–306, 305n

  • melanomas, 146, 159, 159n, 161

  • melatonin, 202–203

  • Mendelian randomization (MR), 53–54, 53n, 302

  • Merrill, Thomas, 284

  • metabolic dysfunction and metabolic syndrome, 88–110

    • as Alzheimer’s disease risk factor, 72, 109, 196–197, 199, 200–201

    • background, 17, 88–90

    • biomarkers for, 108–109

    • as cancer risk factor, 72, 107–108, 109, 152–153

    • as cardiovascular risk factor, 17, 72, 109

    • criteria for, 93–96

    • evolution and, 103–105

    • fat storage and, 96–100, 99

    • fructose and, 104–107

    • genetics of, 199

    • insulin resistance and, 100–102

    • liver and, 88–93, 98, 99, 107–108

    • Medicine 2.0 vs. Medicine 3.0 approaches, 14, 31, 108–110

    • obesity comparison, 93–94, 95

    • sleep and, 356–358

    • as type 2 diabetes risk factor, 72, 99, 102–103

  • metastatic cancer, 140–142, 144, 146, 147–149, 165–167

  • metastatic melanoma, 165

  • metformin, 87

  • mild cognitive impairment (MCI), 190, 363

  • mindfulness mediation practice, 399, 402–403, 406

  • “miraculous” survivors, 155, 158–159

  • mismatch-repair deficiency, 162

  • mitochondria, 224, 237, 238–242, 242n

  • mitochondrial biogenesis, 82

  • monkey studies, 312–316, 314n

  • monounsaturated fats, 133

  • mono-unsaturated fatty acids (MUFA), 335–336n, 335–340

  • Morano, Emma, 60

  • Morningness/Eveningness Questionnaire (MEQ), 368n

  • morphine, 365

  • Mortality (Hitchens), 148–149

  • MRI, for lung cancer screening, 171–172, 172n

  • mTOR (mechanistic target of rapamycin), 77–78, 77n, 82, 85, 341

  • Mukherjee, Siddhartha, 155, 156, 158

  • multiple myeloma, 152, 153

  • muscle, 96, 97, 98, 99. See also strength training

N

  • NAFLD (nonalcoholic fatty liver disease), 91, 92, 93, 98, 107–108, 109–110, 344

  • NASH (nonalcoholic steatohepatitis), 91, 92–93, 102, 344, 357

  • National Institutes of Health, 71, 187, 313–316, 314n

  • neurodegenerative diseases, 83, 177–180, 186–193, 204–205, 209, 363. See also Alzheimer’s disease

  • New England Centenarian Study, 62, 63–65

  • nicotinamide riboside (NR), 79

  • Niotis, Kellyann, 187, 191

  • noncalcified plaques, 124, 125

  • non-Hodgkin’s lymphoma, 143

  • nutritional biochemistry, 291–306

    • alcohol, 320–321

    • background, 291–294

    • caloric restriction, 309, 310, 311–316

    • with cancer treatments, 155–156

    • carbohydrates, 318, 322–330, 347

    • conclusion, 346–348

    • dietary restrictions, 309, 310, 317–320

    • emotional health and, 401

    • fasting (time-restricted eating), 156–157, 309, 310–311, 340–346

    • fats, 304–306, 318, 329–330, 335–336n, 335–340, 347

    • goals of, 294–296

    • as longevity tactic, 48

    • overview, 17, 48–49

    • protein, 17, 318, 329–334, 330n

    • quantity and quality of food, 315–316

    • research on, 296–306, 305n

    • Standard American Diet, 308–311, 326–327

  • nuts, 304–306, 337

O

  • obesity, 93–94, 95, 107–108, 152, 153, 369n

  • obstructive sleep apnea, 369, 369n

  • O’Connor, Anahad, 127–128, 130

  • Ohsumi, Yoshinori, 83

  • old-man blood, 356

  • olive oil, 304–306

  • Olshansky, S. Jay, 71

  • omega-3 fatty acids, 200, 204, 336–340

  • oral glucose tolerance test (OGTT), 109, 109n

  • oral health, 203

  • orexin, 365–366

  • ovarian cancer, 152

  • Overton, Richard, 59

  • oxidative stress, 120–121

P

  • pancreas, 98, 99, 101

  • pancreatic adenocarcinoma, 162

  • pancreatic cancer, 2, 146–147, 152

  • paradigm shift, 20–35

    • author’s quest to understand, 20–25

    • medical history eras, 23–28

  • overview, 17–19

  • risk assessment, 22–25

  • parasympathetic nervous system, 272, 405

  • Parkinson’s disease, 83, 179, 185, 189, 190, 192–193

  • Parsley, Kirk, 352–354

  • Pasteur, Louis, 26, 26n

  • PCSK9 inhibitors, 129–130, 138

  • PD-1, 161, 162

  • pembrolizumab (Keytruda), 161

  • Perel, Esther, 50, 390, 392, 397

  • performance-based esteem, 394, 397, 410

  • Perls, Thomas, 63, 64, 65

  • P. gingivalis, 203

  • physical stamina. See cardiorespiratory fitness

  • PI3-kinases (PI3K), 152–154

  • PI3K inhibitors, 154–155, 156

  • Pittsburgh Sleep Quality Index, 367–368, 367n

  • plant-based protein, 333

  • platinum-based chemotherapy, 163

  • Plato, 180–181

  • polyunsaturated fatty acids (PUFA), 335–336n, 335–340, 337n

  • Pott, Percival, 297n

  • Prasad, Vinay, 163

  • prediabetes. See insulin resistance

  • PREDIMED (PREvención con DIeta MEDiterránea) study, 304–306, 305n

  • prostate cancer, 147, 167, 168–169

  • protein (dietary), 17, 318, 329–334, 330n

  • protein aggregates, 83

  • protein supplements, 333–334

  • PSEN1 mutation, 182, 185

  • psychedelics, 399

  • Psychological Counseling Services, 397–399, 400

  • PTEN gene, 145–146, 152

  • pulling motions, 258, 261–262

Q

  • Quviviq (daridorexant), 365–366

R

  • race car analogy, 266–267, 277–278, 284

  • randomized controlled trials, 50–51, 54–55

  • Rano Kau, 75

  • rapamycin, 74–79, 77n, 83–87

  • Rapa Nui (Easter Island), 73–76, 87n

  • reactive oxygen species (ROS), 120–121

  • Real, Terrence, 377, 390–392, 404

  • Reaven, Gerald, 93–94, 109

  • rectal cancer, 153, 167, 169–171, 169–171nn

  • red meat, 299–300

  • reframing, 392–394, 404

  • renal (kidney) cancer, 152, 153, 159, 159n

  • resilience of centenarians, 72

  • résumé virtues, 394

  • resveratrol, 78–79

  • Rintala, Michael, 271, 276n

  • risk assessment, 22–25, 53–55

  • The Road to Character (Brooks), 394

  • Rosenberg, Steve, 140–142, 145, 156, 158–160, 320

  • rosuvastatin (Crestor), 137–138

  • Roth, Martin, 181, 184, 194

  • Rowley, Theresa, 60

  • rucking (carrying heavy stuff), 256–257, 405–406

S

  • Sabatini, David, 74–75, 76–78

  • Sagan, Carl, 88

  • San Millán, Iñigo, 237–239, 240, 241, 242n, 243–244

  • saturated fatty acids (SFA), 118, 133, 133n, 335–336n, 335–340

  • saunas, 204

  • scientific method, 27

  • Sehgal, Aji, 75–76

  • Sehgal, Suren, 75–77, 87n

  • “self-driving” car analogy, 30

  • self-talk, 395, 403–404

  • Semmelweis, Ignaz, 26–27

  • Seneca, 403

  • “senile dementia,” 181

  • sensitivity, 167–168

  • Shakespeare, William, 181, 403

  • shame, 391, 397, 404

  • Shulman, Gerald, 97, 100

  • sleep, 349–376

    • background, 349–352

    • brain health and, 359–364

    • cardiovascular disease and, 358–359

    • conclusion, 376

    • continuous glucose monitoring during, 327, 329, 330

    • emotional health and, 361–362, 401

    • environment for improving, 369–374

    • importance of, 47, 202–203, 352–354

    • insomnia, 363, 365–366, 373, 376

    • length of sleep cycle, 354–355

    • medications for, 364–367

    • metabolic dysfunction and, 356–358

    • overview, 49

    • process for improving, 321, 367–369

    • rules for, 374–375

    • stages of, 360–362, 362n

  • sleep apnea, 369, 369n

  • sleep opportunity, 375

  • sleep questionnaires, 367–368, 367n, 368n

  • sleep restriction, 373, 376

  • smoking, 59–60, 61, 120–121, 125–126, 133, 196

  • Sniderman, Allan, 114, 118–119, 136

  • soda, 60, 107, 109, 109n, 292–293

  • “soft” plaques, 124, 124n, 125

  • specificity, 167–168

  • spontaneous remission, 140–142, 158–159, 164

  • stability training

    • background, 263–265

    • breathing, 272–277, 276n

    • caveats, 271–272, 283–284

    • exercises, 261–262, 268–271, 269, 277–287

    • importance of, 265–268

    • overview, 236

    • power of, 287–290

    • preparation overview, 236

    • slow down to go fast with, 284

    • stability defined, 266

    • trainers and, 283–284

  • Standard American Diet (SAD), 308–311, 326–327

  • Stary, Herbert C., 119

  • statins, 133–134, 136–139, 305, 305n

  • step-up exercise, 285–287

  • stomach cancer, 140–142, 153

  • STOP-BANG questionnaire, 369, 369n

  • strength training

    • background, 216–218, 252–253

    • benefits of, 201–202, 223–228, 254–256

    • foundation training, 255–262

    • overview, 236

    • power of, 287–290

    • preparation overview, 236

    • protein consumption and, 330, 330n

  • Streptomyces hygroscopicus, 75

  • stress, 202–203, 327, 329, 330, 357–358, 373, 374–375

  • stroke (cerebrovascular disease), 63, 112–113, 195–196, 224

  • Stromsness, Michael, 269–270, 271, 284

  • substance-abuse crisis, 381–382

  • suicide, 381–382, 400

  • Sun Tzu, 36, 41

  • sympathetic nervous system, 272

  • “Syndrome X,” 94

T

  • TAME (Targeting Aging with Metformin) trial, 87

  • Tanchou, Stanislas, 209

  • tasks of daily living, 46, 64, 231–234, 401

  • tau, 182, 183, 184, 362–363

  • Taylor, Linda, 159

  • T cells, 158–161, 163–164

  • Teagno, Lorie, 390, 392, 397

  • Templeton, John, 235

  • Thatcher, Margaret, 140

  • “This Is Water” (Wallace), 393

  • Thompson, Craig, 151

  • time-restricted eating (TR), 156–157, 309, 310–311, 340–346

  • Tithonus, 10, 63

  • TNF-alpha, 198

  • toe yoga, 278–279, 279n

  • Tomlinson, Bernard, 181, 184, 194

  • TOR (target of rapamycin), 77n. See also mTOR

  • transcription factors, 69–70

  • The Transformed Cell (Rosenberg), 141

  • trauma, 384–388

  • Trauma Tree, 386, 387–388

  • trazodone, 366, 366n

  • triglycerides, 94, 98, 108, 126

  • Truman, Harry S., 111

  • tumor-infiltrating lymphocytes (TILs), 164, 164n

  • “tumor suppressor” genes, 146

  • Tutu, Desmond, 7

  • type 2 diabetes

    • causes, 109

    • as disease of civilization, 102, 209

    • impact of, 152, 154, 196–197

    • Medicine 2.0’s approach to, 13–14, 13n

    • risk factors, 72, 99, 102–103, 357

  • Tyson, Mike, 55

U

  • University of Wisconsin–Madison monkey study, 313–316, 314n

  • uric acid, 104–106, 108, 126

  • US Airways emergency landing, 410–411

V

  • Valium, 365

  • van Cauter, Eve, 356–357, 358

  • Vander Heiden, Matthew, 151

  • vascular dementia, 191, 196, 197

  • vegan Standard American Diet, 308

  • very-early-onset Alzheimer’s disease, 182

  • visceral fat, 98–100, 99, 126

  • vitamin B, 132n, 204

  • vitamin D, 204

  • VLDLs (very-low-density lipoproteins), 108, 117n, 131, 132, 137, 139

  • VO2 max, 220–221, 223, 244–252, 246, 250–251n, 250

W

  • Wallace, David Foster, 392–393

  • Warburg, Otto, 149

  • Warburg effect, 150, 151–152, 151n, 157

  • Watson, James, 150–151

  • weight training. See strength training

  • Weinberg, Robert, 149

  • Weiss, Ethan, 342

  • Welles, Orson, 307

  • Whipple Procedure, 2

  • White, Andy, 401

  • Whitehall II cohort study, 190

  • Wilkins, Maurice, 150

  • Willcox, Bradley, 69

  • Women’s Health Initiative (WHI), 303–304

X

  • Xanax, 366

Y

  • Yassine, Hussain, 198

Z

  • Zelman, Samuel, 90–91, 107

  • zone 2 training, 237–244

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