Healthy Aging: The Evidence by Area

Endpoint: Major cardiovascular events (PREDIMED)

Endpoint: Cardiovascular death, heart attack and stroke in people with cardiovascular disease or type 2 diabetes

Endpoint: Cardiovascular death, heart-failure hospitalization and kidney-failure progression

Endpoint: Systolic and diastolic blood pressure (DASH, DASH-Sodium)

Endpoint: Systolic and diastolic blood pressure (Cochrane meta-analysis)

Endpoint: Blood pressure in people drinking more than two drinks a day

Endpoint: Total and LDL Low-density lipoprotein cholesterol, the cholesterol fraction most closely tied to plaque in the arteries. cholesterol

Endpoint: LDL cholesterol

Endpoint: LDL cholesterol

Endpoint: Blood pressure reduction (validated surrogate)

Endpoint: Resting systolic blood pressure

Endpoint: Cardiovascular events and cardiovascular mortality

Endpoint: All-cause mortality and hospitalization in heart failure (Q-SYMBIO)

Endpoint: Disability-free survival in healthy adults aged 70 and over

Endpoint: Chronic disease in healthy postmenopausal women, including breast cancer, stroke and blood clots

Endpoint: Objectively measured muscle size and strength

Endpoint: VO2max, objectively measured

Endpoint: VO2max, objectively measured

Endpoint: Strength recorded by an instrument (one-repetition maximum or dynamometer), a functional endpoint

Endpoint: Strength (one-repetition maximum) gained during resistance training, healthy adults

Endpoint: Falls in older adults

Endpoint: Cardiorespiratory fitness (measured VO2max) in inactive adults

Endpoint: Muscle strength / hypertrophy (objective, low-certainty)

Endpoint: Response and remission in treatment-resistant major depression on blinded clinician-rated scales (HAM-D, MADRS)

Endpoint: Postoperative cognitive dysfunction in older adults having major surgery, on the Montreal Cognitive Assessment

Endpoint: Depression scores, response and remission in winter seasonal depression and non-seasonal major depression on clinician-rated scales (SIGH-SAD, HAM-D, MADRS)

Endpoint: Self-reported anxiety, depression and pain

Endpoint: Depression symptom scales (HAM-D and similar)

Endpoint: Cognitive symptoms in mild to moderate dementia

Endpoint: Self-reported anxiety

Endpoint: Self-rated hearing-related quality of life and everyday communication in adults with mild to moderate hearing loss

Endpoint: Objectively measured daytime wakefulness in moderate to severe obstructive sleep apnea

Endpoint: Alertness and cognitive performance on objective tests (reaction time, attention lapses, sleep latency, task scores) in the 1 to 3 hours after a nap

Endpoint: Insomnia: sleep onset, time awake after sleep onset and sleep efficiency, from sleep diaries

Endpoint: Apnea severity, daytime sleepiness and blood pressure in obstructive sleep apnea

Endpoint: Apnea severity and daytime sleepiness in implanted adults who cannot use CPAP

Endpoint: Self-reported sleep quality

Endpoint: Daytime sleepiness and apnea-hypopnea index after two to four months of daily mouth and throat exercises

Endpoint: Sleep onset timing in delayed sleep phase disorder (B) and jet lag symptoms after flights across five or more time zones (B). In ordinary adult insomnia the effect on sleep onset is a few minutes and the adult-only pooled analysis is null, so that use is C. The antioxidant claim rests on no randomized clinical trial and carries no letter.

Endpoint: Apnea-hypopnea index in obstructive sleep apnea with obesity; onset of type 2 diabetes in prediabetes

Endpoint: Body weight and HbA1c

Endpoint: HbA1c, fasting glucose and LDL cholesterol in type 2 diabetes and dyslipidemia

Endpoint: Fasting glucose and HbA1c

Endpoint: Glycemic markers (blood sugar)

Endpoint: LDL cholesterol (and HbA1c in type 2 diabetes)

Endpoint: Short-term energy intake and body weight

Endpoint: Blood pressure against an unrestricted diet, adults without diabetes

Endpoint: Muscle and mitochondrial gains from exercise training in healthy older adults

Endpoint: Colorectal cancer mortality (hard endpoint An outcome that matters directly to a person and is counted without judgment, such as death, heart attack, stroke or fracture.), graded separately by test

Endpoint: All-cause, cardiovascular and cancer mortality in adults unselected for disease

Endpoint: Incidence of late-stage (III and IV) cancer at diagnosis, a stage-shift surrogate for cancer mortality

Endpoint: Cancer mortality or all-cause mortality in asymptomatic screened adults

Endpoint: Muscle insulin sensitivity in prediabetic postmenopausal women, which is the use the Grade C rests on. Blood NAD+ Nicotinamide adenine dinucleotide, a molecule cells use in energy metabolism. Its level falls with age in some tissues. concentration is also Grade C and is a mechanistic marker, not an outcome. Longevity, healthspan and mortality are Grade D: no human trial has tested them.

Endpoint: Six-minute walk in peripheral artery disease; blood NAD+; cognition and insulin sensitivity tested without benefit; early Parkinson disease tested with harm found

Endpoint: Metabolic markers and pace of aging in healthy non-obese adults

Endpoint: DNA methylation age, an epigenetic clock A test that estimates biological age from chemical marks on DNA (DNA methylation).

Endpoint: Visceral adiposity and physical function (chair-stand repetitions) in older adults

Endpoint: No randomized trial of fisetin as a senolytic A compound intended to clear senescent cells: older cells that have stopped dividing but remain in tissue. for aging has reported results. Small randomized trials exist in other uses, including a null placebo-controlled crossover in Gulf War illness. Route 1: animal senolytic data only.

Endpoint: No randomized trial of spermidine on lifespan or mortality has been run. A 12-month randomized trial in older adults with subjective cognitive decline (SmartAge) found no effect on memory. Route 1: animal lifespan data plus observational epidemiology.