Cardiorespiratory fitness is an independent predictor of all-cause and cardiovascular mortality; improving it is broadly beneficial (Liu et al., J Clin Endocrinol Metab, 2025). No dedicated interventional-mortality trial retrieved.

Aerobic training improves cardiometabolic health but is inferior to resistance training for muscle mass (Lucio et al., Sci Rep, 2026). Specific “Zone 2” outcome trials not retrieved.

First-line for sarcopenia; superior to aerobic exercise for muscle mass, with moderate-certainty gains in strength and physical performance (Lucio et al., Sci Rep, 2026).

~25–40% of GLP-1/GIP weight loss is fat-free mass; relative muscle preservation is generally maintained but absolute lean loss is a concern—pair with resistance training/protein (Bhandarkar et al., Curr Opin Endocrinol Diabetes Obes, 2025; Beaudart et al., Drugs, 2026; Liu et al., J Clin Endocrinol Metab, 2025).

Large trials show reductions in MACE, all-cause mortality, HF hospitalization, renal decline, plus weight/glycemic benefit in diabetes and obesity (Nauck et al., Lancet, 2026; Valabhji et al., Lancet, 2026; ADA Standards of Care, 2026).

Insulin resistance/visceral adiposity drives cardiometabolic risk and cellular senescence (Forman et al., JACC, 2023). Optimal screening test/threshold not established in retrieved data.

Strong evidence in insulin-treated diabetes; use in metabolically healthy/prevention populations is not supported by retrieved outcome data.

Validated for body composition and bone density; central to trials of lean-mass change (Jobanputra et al., Diabetes Metab Res Rev, 2026). Not an outcome-altering “test” by itself.

Visceral adiposity is mechanistically linked to inflammation, senescence and CVD risk (Forman et al., JACC, 2023).

Endorsed as a functional aging/mortality-associated measure in geroscience frameworks (Campisi et al., Nature, 2019).

Adequate protein plus resistance training mitigates lean-mass loss and frailty, especially during weight loss (Forman et al., JACC, 2023; Lucio et al., Sci Rep, 2026).

Widely used adjunct to resistance training; dedicated longevity/outcome source not retrieved.

Improves body composition, insulin sensitivity, lipids and inflammation; benefits often overlap with caloric reduction, long-term/mortality data lacking (Minari & Pisani, J Nutr, 2026; Wu et al., Front Med, 2025).

Most robust lifespan/healthspan intervention in animals; CALERIE shows improved cardiometabolic and aging markers in humans, but controversial in non-obese older adults (Forman et al., JACC, 2023; Mihaylova et al., Cell Metab, 2023).

Improve metabolic surrogates; long-term human outcome data limited (Mihaylova et al., Cell Metab, 2023).

No dedicated longevity-outcome source retrieved; evidence strongest for select epilepsy/metabolic uses, not general healthspan.

RCT (PREDIMED, CORDIOPREV) and large meta-analyses show ~30% reduction in major CV events and lower CV mortality (Volpe et al., Nutrition, 2026; Pagidipati et al., Nat Rev Cardiol, 2025; Guasch-Ferré & Willett, J Intern Med, 2021).

Most accurate atherogenic-particle marker; superior to LDL-C/non-HDL-C for risk prediction and residual risk, more reliably measured (Sniderman et al., JAMA Cardiol, 2022; De Oliveira-Gomes et al., Circulation, 2024; Galimberti et al., Pharmacol Res, 2023).

Genetically determined, causal, independent ASCVD/aortic-stenosis risk factor; measure once in every adult (Mora & Kronenberg, JAMA, 2025; 2026 ACC/AHA Dyslipidemia Guideline; 2025 ESC/EAS Focused Update). Targeted therapy still investigational.

Preferred test to refine statin decisions in borderline/intermediate-risk adults; CAC=0 reclassifies to low risk (“power of zero”) (Glynn/Khan/Greenland, JAMA, 2025; Grundy & Stone, Am J Med, 2021; Greenland et al., JACC, 2018).

Strong for symptomatic chest-pain evaluation; role as an asymptomatic-screening/longevity tool not supported by retrieved outcome data.

Lp(a)-associated risk is independent of hs-CRP; hs-CRP adds inflammatory-risk information but is a weaker reclassifier than CAC (Small et al., JAMA Cardiol, 2024; Glynn/Khan/Greenland, JAMA, 2025).

Intensive BP control reduces CV events (guideline consensus). No dedicated trial source retrieved in this search.

LDL/apoB lowering causally reduces ASCVD with no clear lower threshold; PCSK9i (FOURIER, ODYSSEY) and bempedoic acid reduce events, including statin-intolerant patients (Preiss et al., JACC, 2020; Ruhela et al., Coron Artery Dis, 2025; FDA labels: Repatha, Praluent, Nexletol).

Associated with vascular risk but lowering it has not reduced events in trials; low-value routine test. No dedicated source retrieved.

High specificity and improving PPV, but the randomized NHS-Galleri trial did not reduce late-stage cancer incidence; no mortality benefit yet, not FDA-approved/guideline-endorsed (Sasieni et al., NEJM, 2026; Bermúdez-Guzmán, JAMA Intern Med, 2026; Hoffman et al., Cancer, 2025; Robbins, NEJM, 2024).

No dedicated outcome source retrieved; high false-positive/incidentaloma burden, no mortality evidence as a screening tool.

Colorectal screening reduces CRC mortality; blood-based tests are emerging adjuncts still requiring validation (Shaukat et al., AGA Clinical Practice Update, 2025).

Guideline-endorsed for high-risk smokers with proven mortality benefit (general consensus; dedicated trial source not retrieved here).

Established value in high-risk/familial settings for guiding surveillance and prevention; population-wide use less supported. No dedicated source retrieved.

p-tau217 approaches CSF/PET accuracy for amyloid status and tracks progression; incorporated into 2024 NIA-AA research criteria (Ashton et al., Nat Med, 2022; Llibre-Guerra et al., Nat Rev Neurol, 2025; Álvarez-Sánchez et al., Sci Rep, 2025).

Strongest sporadic-AD genetic risk factor; lowers the p-tau217 threshold for tau spread in allele-dose manner, informing screening/treatment timing (Steward et al., Brain, 2026).

Cognitive reserve is protective; direct causal training-to-dementia-prevention evidence is limited. No dedicated source retrieved.

Hearing loss is a leading modifiable dementia risk factor; hearing-aid use is associated with ~17–19% lower dementia/cognitive-decline risk, though the ACHIEVE RCT showed benefit mainly in higher-risk subgroups (Yeo et al., JAMA Neurol, 2023; Cribb et al., Neurology, 2026).

Both insufficient and disordered sleep raise MCI/dementia risk, plausibly via impaired amyloid clearance (Mayer et al., Front Neurosci, 2024).

Sleep-disordered breathing is linked to vascular dementia; CPAP may improve cognition (Mayer et al., Front Neurosci, 2024).

Mechanistic link between sleep, glymphatic amyloid/tau clearance and neurodegeneration (Mayer et al., Front Neurosci, 2024).

Approved for early symptomatic AD (biomarker-confirmed); prevention trials in asymptomatic amyloid-positive individuals ongoing (Llibre-Guerra et al., Nat Rev Neurol, 2025).

Longevity interventions measurably lower epigenetic age; pharmacologic agents (anti-TNF, metformin) show larger/more reproducible effects than supplements (Sehgal et al., Nat Med, 2026).

Aging biomarker of uncertain clinical utility; no dedicated intervention-outcome source retrieved.

Extend healthspan in model organisms; human data limited and mixed, and NR showed no lifespan benefit in the NIA ITP (Espinoza et al., J Gerontol A, 2023; Kritchevsky & Cummings, JAMA, 2025; Guarente et al., Cell Metab, 2024).

Pleiotropic aging pathways and observational mortality benefit in diabetes; geroprotective claim being tested (TAME, VA-IMPACT), not proven in non-diabetics (Forman et al., JACC, 2023; Hu et al., Diabetes Metab Res Rev, 2026; Espinoza et al., J Gerontol A, 2023).

Most consistent lifespan extender in NIA ITP mice; human trials (e.g., PEARL) target aging biomarkers; immunosuppression/dosing concerns (Kritchevsky & Cummings, JAMA, 2025; Partridge et al., Nat Rev Drug Discov, 2020; Chen et al., Front Aging, 2025).

Improve healthspan in rodents; human trials in progress with inconsistent epigenetic-age effects so far (Chaib et al., Nat Med, 2022; Espinoza et al., J Gerontol A, 2023; Sehgal et al., Nat Med, 2026).

Extends lifespan in ITP mice (notably males); human geroprotection unproven (Kritchevsky & Cummings, JAMA, 2025; Campisi et al., Nature, 2019).

Reduce HF hospitalization, CV death and renal progression in diabetes/HF/CKD (ADA Standards of Care, 2026; FDA labels: Jardiance, Farxiga, Invokana). General-healthspan use unproven.

Autophagy-inducing geroprotector in animals; early human trials only (Partridge et al., Nat Rev Drug Discov, 2020; Guarente et al., Cell Metab, 2024).

Enhances mitophagy with early human muscle-function signals; longevity outcomes unproven. No dedicated primary trial retrieved.

SRT compounds extend rodent lifespan in some studies; human geroprotection not established (Campisi et al., Nature, 2019).

Preclinical aging-modulation interest; robust human longevity data not retrieved.

Core nutrient-sensing/energy pathway targeted by metformin and exercise (Hu et al., Diabetes Metab Res Rev, 2026; Forman et al., JACC, 2023).

Fundamental aging mechanism modulated by fasting, spermidine, mTOR inhibition (Mihaylova et al., Cell Metab, 2023; Forman et al., JACC, 2023).

Central aging hallmark; marketed mito supplements did not extend lifespan in the ITP (Kritchevsky & Cummings, JAMA, 2025).

Recognized aging hallmark targeted indirectly by mTOR/autophagy interventions (Forman et al., JACC, 2023).

No validated human anti-aging outcome data retrieved; largely investigational.

Promising rejuvenation in animal models; no human data (Chen et al., Front Aging, 2025).

Systemic-milieu “young blood/klotho” concept is preclinical; human anti-aging evidence not retrieved (Chaib et al., Nat Med, 2022).

α-Klotho overexpression extends healthspan/lifespan in mice; human application experimental (Chaib et al., Nat Med, 2022).

No validated longevity-outcome source retrieved; largely unregulated/experimental.

Not supported for healthy aging; risk of adverse metabolic/neoplastic effects. No supportive longevity source retrieved.

In postmenopausal women, limited to HSDD via transdermal route; compounded/pellet forms discouraged (Pilnik et al., ALEG Position Statement, Climacteric, 2025; Lara et al., Cochrane, 2025). Male TRT evidence not retrieved here.

Effective for vasomotor/genitourinary symptoms; androgen add-on evidence limited (Lara et al., Cochrane, 2025).

Systemic DHEA not recommended for sexual/menopausal symptoms (Grade A against); vaginal DHEA approved only for genitourinary syndrome (Pilnik et al., Climacteric, 2025; Lara et al., Cochrane, 2025).

No dedicated healthspan source retrieved; treat overt disease, avoid treating euthyroid “optimization.”

Symptom-directed hormonal/non-hormonal care; androgen benefit in perimenopause is insufficiently supported (Lara et al., Cochrane, 2025).

Chronic low-grade inflammation is a core aging driver; anti-inflammatory/anti-TNF interventions lower epigenetic age (Sehgal et al., Nat Med, 2026; Campisi et al., Nature, 2019).

Established aging hallmark; targeted therapies investigational (Campisi et al., Nature, 2019).

Modifiable via diet (e.g., Mediterranean) with plausible cardiometabolic links; causal outcome data developing (Hernández-Cacho et al., Curr Atheroscler Rep, 2026).

Associated with systemic/CV risk; no dedicated causal-outcome source retrieved.

RZV/LZV prevent herpes zoster (moderate-certainty); RSV vaccines recommended for all ≥75 and high-risk 60–74, ~75% effective against hospitalization (Gomes et al., Cochrane, 2023; ACIP/Britton et al., MMWR, 2024; Del Riccio et al., Drugs Aging, 2026).

No validated human outcome data retrieved.

Finnish cohort data link frequent sauna use to lower CV and all-cause mortality in dose-response fashion; mechanisms include reduced arterial stiffness/BP (Laukkanen et al., BMC Med, 2018; Laukkanen & Kunutsor, Prog Cardiovasc Dis, 2019; Nagai & Tanaka, Int J Environ Res Public Health, 2026).

No robust human outcome source retrieved; benefits largely anecdotal/mechanistic.

Studied for epigenetic-age effects with inconsistent results; no longevity outcome evidence (Sehgal et al., Nat Med, 2026).

No validated longevity/systemic-outcome source retrieved.

Growing concern; causal human outcome data limited. No dedicated source retrieved.

Overt toxicity is well defined; “burden testing” in asymptomatic adults not outcome-supported. No source retrieved.

Air pollution is an established CV/respiratory and dementia risk factor (general consensus; dedicated source not retrieved here).

Reducing alcohol lowers CV and injury risk; alcohol plus sauna raises arrhythmia/sudden-death risk (Szafraniec et al., Sci Rep, 2025; Laukkanen & Kunutsor, Prog Cardiovasc Dis, 2019).

Robust association between social engagement and lower mortality/dementia; also a hearing-loss→dementia pathway (Cribb et al., Neurology, 2026).

Observational/ecological; no dedicated causal source retrieved.

Autonomic marker; sauna and lifestyle stabilize autonomic function (Laukkanen et al., BMC Med, 2018). Outcome-level HRV-intervention data limited.

Symptomatic/stress benefits; no dedicated hard-outcome source retrieved.

DEXA-guided diagnosis and treatment reduce fracture risk (guideline consensus); GLP-1 fracture-risk signals still inconclusive (Beaudart et al., Drugs, 2026).

Exercise (resistance/multicomponent) improves performance and reduces fall-related risk (Lucio et al., Sci Rep, 2026).

Gait speed/mobility are validated aging outcomes and intervention targets (Campisi et al., Nature, 2019).

Frailty/multimorbidity are central geroscience trial endpoints and risk stratifiers (Campisi et al., Nature, 2019; Espinoza et al., J Gerontol A, 2023).

No robust longevity/functional-outcome source retrieved; efficacy remains debated.

Useful for activity/sleep/AF detection; direct outcome-improvement evidence for consumer devices not retrieved.

Improving risk stratification (e.g., ASCVD); clinical-utility/outcome data still developing. No dedicated source retrieved.

Value clearest for monogenic/hereditary risk; population screening utility unproven. No dedicated source retrieved.

Organ/aging “clocks” under active development (Kritchevsky & Cummings, JAMA, 2025). Clinical utility not established.

Research-stage aging/risk biomarker discovery; not clinically actionable yet. No dedicated source retrieved.

ML models can integrate markers such as Lp(a) for short-term ASCVD prediction (Ward et al., JACC Adv, 2025). Prospective outcome validation ongoing.

Promising research tools within geroscience; not validated for individual clinical decisions (Kritchevsky & Cummings, JAMA, 2025).

No dedicated systemic-outcome source retrieved; photoprotection is standard preventive care.

AREDS-type supplementation slows advanced AMD (established consensus; dedicated source not retrieved here).

Cystatin C improves GFR estimation and risk prediction (established consensus; dedicated source not retrieved here).

Metabolic driver of CV/hepatic risk; semaglutide is FDA-approved for MASH with F2–F3 fibrosis, and incretins regress steatosis (FDA label: Wegovy; Nauck et al., Lancet, 2026).

Aligns with the geroscience hypothesis—targeting shared aging mechanisms to compress morbidity; framework-level rather than a single validated intervention (Kritchevsky & Cummings, JAMA, 2025; Espinoza et al., J Gerontol A, 2023).