| Dietary restriction by 1% yeast medium | Dietary restriction by be reducing yeast content in medium to 1% extends the lifespan [19968629]. | Fly | — | — | — |
| Dietary restriction on high-fat diet | Dietary restriction on a high-fat diet increases both mean and maximum lifespan by 36% compared to the high-fate diet control group [22509016]. | Mouse | +36 | — | +36 |
| DMSO treatment | Treatment with 0.5 and 2% DMSO increases lifespan by 24.4 and 23.0%, respectively. 0.5% DMSO does not affect progeny number or lifespan under thermal stress. Treatment with 0.5% DMSO enhances the mRNA levels of hsp-16.2, hsp-70, lys-7, old-1, and sod-5 by 2.5, 2.9, 1.3, 2.3, and 4.5-fold, respectively, as well as the protein level of lys-7 by 1.5-fold. Lifespan extension confered by DMSO depends on sir-2.1 and daf-16 but not on eat-2 or hsf-1 [20828537]. | Worm | +23.0 to +24.4 | — | — |
| Eleutherococcus senticosus treatment | Plant adaptogen Eleutherococcus senticosus (SHE-3; alias Acantopanax senticosus) increase stress resistance and mean lifespan in a dose-dependent manner. 250 microgram/ml SHE-3 signinifanclty increases lifespan between 10 and 20% 9 (P < 0.001), increase maximum lifepsan with 2-3 days and pospones the moment when the first individuals die. With higher concentrations, the effect is weakerm wheras at the highest concentrations (2500 microgram/mL) a lifespan shortenening effect of 15-25% (P < 0.001) occurs. Treatment with SHE-3 induces translocation of DAF-16 and activation of HSP-16 [18536978]. | Worm | +10 to +20 | — | — |
| Ganodermasides A treatment | Application of Ganodermasides A extends the replicative lifespan in K6001 strain by regulating UTH1 expression [20093034]. | Yeast | — | — | — |
| Ganodermasides B treatment | Application of Ganodermasides B extends the replicative lifespan in K6001 strain by regulating UTH1 expression [20093034]. | Yeast | — | — | — |
| Ganodermasides C treatment | Application of gonadermasides C significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 [21512225]. | Yeast | — | — | — |
| GGTI-298 treatment | Treatment with type 1 geranylgeranyl transferase inhibitor GGTI-298 increases lifespan [22737247]. | Fly | — | — | — |
| Gonadermasides D treatment | Application of gonadermasides D significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 [21512225]. | Yeast | — | — | — |
| Hesperidin treatment | Hesperidin derived from the Citrus genus extends replicative lifespan at doses of 5 and 10 microMolar. Hesperdin inihibts ROS and UTH1 gene expression, but increases Sir2 and SOD gene expression. UTH1 and SKN7 are involved in lifespan extension mediated by hesperidin [22484922]. | Yeast | — | — | — |
| High fat diet | Lifelong feeding of a high-fat diet markedly reduces lifespan of mice by about 20% for both mean and maximum lifespan [22509016]. | Mouse | -20 | — | -20 |
| High sugar low protein diet | A high sugar low protein diet increases the lifespan, but not resistance to acute oxidative stress [22672579]. | Fly | — | — | — |
| Icariin treatment | Icariin and its derivate icariside II extend lifespan. Animals treated with icariin have high levels of icariside II [22216122]. | Worm | — | — | — |
| Icariside II treatment | Icariside II and its derivate icarrin extend lifespan. Animals treated with icariin have high levels of icariside II. Icariside II also increases thermo and oxidative stress tolerance, slow locomotion decline in late adulthood and delay the onset of paralysis mediated by polyQ and ABeta(1-42) proteotoxicity. Lifespan extension by Icariside II is dependent on IIS, since daf-16(mu86) and daf-2(e1370) fails to sho exhibit lifespan extension upon icariside treatment. Incariside II treatment upregulates expression of DAF-16 targets in wild-type. HSF-1 has also a role in icariside II-dependent lifespan extension [22216122]. | Worm | — | — | — |
| Intermittent fasting | Intemittent fasting diet increases survivorship and improves insuli sensitivity of normal males, but fails to affect either parameter in GHRKO mice [19747233]. | Mouse | — | — | — |
| Jugelone treatment | High jugelone concentrations led to premature death. Low juglone concentrations are tolerated well and cause a prolongation of lifespan that is associated with increased expression of small heat-shock protein HSP-16.2, enhanced glutathione levels, and nuclear translocation of DAF-16. Silencing or deletion of daf-16 prevents jugelone-induced adaptations. RNA-interference for SIR-2.1 has the same effects as daf-16 deletion but does not affect nuclear accumulation of DAF-16. DAF-16- and SIR-2.1-dependent alterations in gene expression after challenge with reactive oxygene species lead to lifespan extension [19597959]. | Worm | — | — | — |
| L-proline supplementation | L-proline supplementation increases lifespan by 5.8 and 13.6% (mean and maximum lifespan) [22482728]. | Worm | +6 | — | +14 |
| L744832 treatment | Farnesyl inhibitor L744832 increases lifespan [22737247]. | Fly | — | — | — |
| LA treatment | LA confers a memory effect, by fixing the lifespan of previous feeding regimen. When animals are switched early in life (12 months) from DR to AL and supplemented with α-lipoic acid the DR typical lifespan extension is maintained, but switching early from AL supplemented with α-lipoic acid to DR blocks the lifespan extending effect [18486188].
LA exhibits the ability to compensate for age-related, long-term memory deficits in old rats [8309958].
| Rat | — | — | — |
| Low calorie diet with low-sugar content | A diet with low-calorie and low-sugar content increase the lifespan, but not resistance to acute oxiditive stress [22672579] | Fly | — | — | — |
| LY294002 treatment | Treatment of Drosophila imago with 5 micromolar LY294002 increases median (by 14%) and maximum (by 16-22%) lifespan (p<0.001) in females and males, respectively [22661237].
Low dose of LY294002 (5 microM) slightly increase the median and maximum lifespan [20017609]. | Fly | — | +14 | +16 to +22 |
| Malnutrition by 0.2% yeast medium | Reduction of the yeast concentration in the medium from 1 to 0.2% shortens the lifespan by invoking malnutrition [19968629]. | Fly | — | — | — |
| Melatonin supplementation | Melatonin administrated with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771]. | Mouse | 0 to +20 | — | — |
| Metformin treatment | Metformin treatment extends healthspan, slows lipofuscin accumulation, extends mean lifespan and prolongs healthful locomotory ability in a dose-dependent manner as well as reduces fecundity. AMPK and its activating kinase LKB1 are essential for these health benefits. Oxidative stress-responsive transcription factor SKN-1/Nrf2 is essential for metformin-confered healthspan too as it must be expressed in both neurons and intestines [20090912]. | Worm | — | — | — |
| Metformin treatment | In fruit fly feeding metformin to adult s results in robust AMPK activation and reduces lipid stores, but does not increase lifespan in either males or females. Administration of high concentration are even toxic [23077661].
| Fly | — | — | — |
GenAge
GenDR
