Table 1.
        Interventions Extending Mean and/or Maximal Lifespan in Wild-Type Mice Fed Normal Chow
,Max Lifespan,Mean Lifespan,Main Mechanism of Action
Dietary Interventions
Calorie restriction,yes,yes,↓ nutrient-sensing pathways
Intermittent fasting,yes,yes,↓ nutrient-sensing pathways
Protein restriction,no,yes,↓ nutrient-sensing pathways
Methionine restriction,yes,yes,↓ nutrient-sensing pathways
Tryptophan restriction,yes,yes,↓ nutrient -sensing pathways
Physical Exercise Interventions
Endurance exercise,no,yes,↑ insulin sensitivity; ↑ AMPK ?
Genetic Interventions
Ames and Snell dwarf,yes,yes,↓ nutrient-sensing pathways
GH receptor KO,yes,yes,↓ nutrient-sensing pathways
IGF-1 R KO,yes (in F),yes (in F),↓ nutrient-sensing pathways
Klotho TG,yes (in M),yes,↓ nutrient-sensing pathways
Fat Insulin Receptor KO,yes,yes,↓ nutrient-sensing pathways
Insulin Receptor Substrate 1 KO,yes (only F),yes (only F),↓ nutrient-sensing pathways
Brain IRS-2 KO,yes,yes,↓ nutrient-sensing pathways
PAPP-A KO,yes,yes,↓ nutrient-sensing pathways
Ribosomal S6 protein kinase-1 KO,yes (only F),yes (only F),↓ nutrient-sensing pathways
FGF-21TG,yes,yes,↓ nutrient-sensing pathways
miR-17TG,?,yes,↓ nutrient-sensing pathways
DGAT1KO,yes (only F),yes (only F),↓ nutrient-sensing pathways
p66shc KO,yes,yes,↓ growth factor-mediated signaling
ATG5 TG,yes,yes,↑ autophagy
Type 5 Adenylyl Cyclase KO,yes,yes,↓ β-adrenergic signaling
Angiotensin II type 1 receptor KO,yes,yes,↓ angiotensin receptor signaling
Catalase targeted to mitochondria TG,yes,yes,↓ oxidative stress (mitochondrial)
Ink4/Arf-TG/TG,no,yes,↓ mitogenic over-stimulation and cell proliferation
C/EBP β/β,yes,yes,↑ mitochondrial biogenesis in white fat cells
Mclk1KO,yes,yes,↓ age-dependent loss of mitochondrial function
Hcrt-UCP2 TG,no,yes,?; ↓ core body temperature
Macrophage migration inhibitory factor KO,yes,yes,↓ inflammation; ↓ insulin pathway
E-DNIκB TG,?,yes,↓ inflammation; ↓ insulin pathway
PKA RIIβ KO,yes,yes,↓ IGF signaling?
RasGRF1 KO,yes,yes,↓ nutrient-sensing pathways
Sirt6 TG,yes (only M),yes (only M),↓ nutrient-sensing pathways (IGF)
Brain-specific Sirt1 TG,yes (only F),yes,↑ mitochondrial function via Sirt1/Nkx2-1/Ox2r
TRPV1 pain receptor KO,yes (only F),yes,modulation of CRTC1/CREB activity
Pharmacological Interventions
Rapamycin,yes,yes,↓ nutrient-sensing pathways (mTOR)
Acarbose,yes,yes,↓ IGF signaling and ↑ FGF-21
Metformin,no,yes,↓ nutrient-sensing pathways (AMPK)
Aspirin,no,yes (only M),↓ inflammation
Nordihydroguaiaretic acid,no,yes (only M),↓ inflammation and oxidative stress
Green tea extract,no,yes (only F),↓ oxidative stress
17α-Estradiol (non-feminizing estrogen),no,yes (only M),? non-genomic actions
Methylene Blue,no,yes (only F),↑ mitochondrial function
Metoprolol,no,yes (in M),↓ β-adrenergic receptor signaling
Nebivolol,no,yes (in M),↓ β-adrenergic receptor signaling