| Gonadermasides D treatment | Application of gonadermasides D significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 [21512225]. | Yeast | — | — | — |
| Ganodermasides C treatment | Application of gonadermasides C significantly increases the replicative lifespan in the K6001 strain by regulating UTH1 [21512225]. | Yeast | — | — | — |
| 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 | — | — | — |
| Oligomycin treatment | Oligomycin (a specific inhibitor of complex V) feeding exends lifespan on ad libitum and prevents an increase in longevity under DR (started in the adulthood) in males [19968629]. | Fly | — | — | — |
| Trehalose treatment | Treatment with trehalose reduces neurodegeneration in a transgenic mouse model of taupathy (human mutant P301S tau mouse. Neuronal survival is evaluated by trehalose. Trehalose induces autophagy in the brain, where the number of neurons containing tau inclusions is significantly reduced as well as the amount of insoluble tau protein and the protein levels of p62. However, trehalose fails to activate autophagy in the spinal cord, where it has no impact on the level of sarkosyl-insoluble tau. Trehalose has also no effect on the motor impairment of human mutant P301S tau transgenic mice [22689910]. | Mouse | — | — | — |
| Methionine restriction | A diet with reduced methionine content extends lifespan and increases body fat [15924568]. | Mouse | — | — | — |
| D-chiro-inositol supplementation | D-chiro-inositol supplementation to the diet extends adult longevity in both male and female animals. 20 microMolar dose of D-chiro-inositol extends median lifespan by 16.7 (p < 0.001) for males and 13% (p < 0.001) for females. Lifespan extension by D-chrio-inositol is accompanied by protection against oxidative and starvation stresses, improvement in health span, and not reduction in fecundity. Nuclear localization of foxo increases in D-chiro-inositol-fed animals [22843669].
| Fly | — | +13 to +16.7 | — |
| Pinitol supplementation | Pinitol (a 3-methoxy analogue of D-chiro-inositol) supplementation to the diet. For both males and females, a 20 microMolar dose of pinitol significantly extends median lifespan by 13% (p < 0.05) and 12.5% (p < 0.05), respectively. Lifespan extension by pinitol is accompanied by protection against oxidative and starvation stresses, improvement in health span, and no reduction in fecundity. Pinitol increases organismal lifespan of both in dietary restriction and ad libitum conditions. Nuclear localization of foxo increases in pinitol-fed animals. Pinitol treatment significantly activates JNK and S6K, but not AKT [22843669]. | Fly | — | +12.5 to +13 | — |
| Mianserin Treatment | Mianserin a serotonin receptor antagonist (used as antidepressant in humans), can increase C. elegans lifespan when given only during adulthood. Lifespan extension is reduced or abolished by mutations that affect serontonin synthesis or serotonin reuptakte at synapses [14,16]. It requires a serontonin receptor and an octopamine receptor which are both inhibited by Mianserin. Mianserin plus DR increase lifespan only by 4% more than DR alone and totally failed to extend lifepan in eat-2(ad1116) mutants. However, mianserin does not appear to reduce food intake [14]. On average, mianserin increases lifespan by 31% by an optimal dose of 50 micromolar, but had little or no effect when given at 250 micromolar. Mianserin failes to increase the lifepsna of mutants lacking serotonin synthesis enzyme TPH-1 and causes a lifespan increase of only 13% in mutant lacking serontin reuptake transporter MOD-5. Mianserin does not increase lifepan of SER-4 or SER-4 mutants. Mianserin increases lifespan by31% when given throughout adulthood, but it only result in 10% lifespan extension when it was gieven beginning at adult day 5. Mianserin also failed to increase lifespan in liquid lifespan assay and in animals grown on solid agarose plates lacking ill-defined component of commoly used agar plates (agar and Bacto peptone). Mianserin increases lifespan of animlas grown at 20 but not at 25 degree Celsius [19686215]. | Worm | — | — | — |
| Resveratrol supplementation | Resveratrol significantly extends the lifespan [12939617]. | Yeast | — | — | — |
| Resveratrol supplementation | Resveratrol supplementation prolongs the lifespan [15254550; 17460219], but not in any case [17875315]. | Worm | — | — | — |
| Resveratrol supplementation | Supplementation with resveratrol extends the lifespan [15254550], but not in always [17875315]. | Fly | — | — | — |
| Resveratrol supplementation | A maximum dose of resveratrol increases the median lifespan by 56% [16461283]. | Fish | — | +56 | — |
| Resveratrol supplementation | Resveratrol conteracts the detrimental effects of a high-fat diet in mice an decreases the risk of death by 30% and thereby reverting it to the level of normal diet. It also partially corrected a subset of the abnormal gene expression profile and insulin as well as glucose metabolism [17086191].
Although resveratrol has a range of beneficial effects in elderly mice, it does not increase the longevity of *ad libitum* fed mice when started midlife [18599363]. Even at high doses and when started in young adulthood reseveratrol supplementation does not increase lifespan on a normal diet [17578509; 20974732].
| Mouse | — | — | — |
| DDS treatment | Treatment with DDS either for the entire lifetime or only during the adult period after the L4 stage extends significantly increases mean and maximum lifespan [20974969]
DDS causes the delay of aging, reduces lipofuscin accumulation and decreases the level of a mitochondrial complex as well as lowers oxygen consumption and enhances oxidative stress resistance [20974969].
DDS-conferred lifespan extension is independent of daf-16 and DR (eat-2 mutants) [20974969].
| Worm | — | — | — |
| concA treatment | The specific V-ATPase inhibitor concanatmycin A (concA) blocks VMA1 or VPH2 overexpression mutations ability to produce normal, tubular mitochondria. Treatment of young cells causes vacuolar acidity and loss of mitochondrial depolarization. Loss of ΔΨ is followed by mitochondrial fragmentation and aggregation that resembles mitochondrial phenotypes present in aged cells [23172144]. | Yeast | — | — | — |
| Carboxyfullerene SOD mimetic treatment | Administration of a small-molecule synthetic enzyme superoxide dismutase mimetic to wild-type (i.e. non-transgenicm non-senescence accelerated) mice starting at middle age significantly extends lifespan and reduces age-associated oxidative stress and mitochondrial radical production. Treatment also improves performance on Morris water maze learning and memory task and therefore rescues age-related cognitive impairment [17079053]. | — | — | — | — |
| Vitamin C treatment | Treatment with 1 mM vitamin C has no effect on lifespan of wild-type, but significantly shortens the lifespan of both isp-1 and muo-6 mutants [21151885].
Supplementation with vitamin C normalizes the median lifespan of wnr-1 and mir-124 mutants, which both exhibit premature aging [23075628]. | Worm | — | — | — |
| 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 | — | — | — |
| Metformin treatment | Chronic treatment of female transgenic HER-2/neu mice with metformin slightly decreases food consumption but fails to reduce body weight or temperature, slows down age-related rise in blood glucose and triglycerides level, as well as the age-related switch-off of estrous function, prolongs mean lifespan by 8% (p < 0.05), the mean lifespan of last 10% survivors by 13.1% and maximum lifespan by 1 month. Metformin treatment significantly decreases incidence and size of mammary adenocarcinomas and increases the mean latency of the tumors [16125352].
Chronic treatment of female outbred SHR mice with metformin slightly modified food consumption but decreases the body weight after the age of 20 months, slows down the age-related switch-off of estrous function, increases mean lifespan by 37.8% mean lifespan of the last 10% survivor by 20.8%, and maximum lifespan by 2.8 month (+10.3%). Treatment with metformin fails to influence blood estradiol concentration and spontaneous tumor incidence in female SHR mice [18728386].
In female SHR mice, metformin increases lifespan lifespan and postpones tumors when started at young and middle but not at old age. Chronic treatment of female outbred SHR mice with metformin started at the age of 3, 9 or 15 months decreases body temperature and postpones age-related switch-off of estrous function. Treatment with metformin started at the age of 3 months increases mean lifespan by 14% and maximum lifespan by 1 month. Treatment started at the age of 9 months insignificantly increases lifespan by only 6%, whereas the treatment started at the age of 15 months fails to increase lifespan. The mean lifespan of tumor-free mice increases by 21% (started at 3 months), by 7% (started at 9 months) and in contrast is reduced by 13% (started at 15 months). If started at 3 and 9 months, metformin delays the first tumors by 22% and 25%, correspondingly [21386129].
Transgenic FVB/N female mice carrying HER-2/neu mammary cancer gene receiving metformin with drinking water 5 days a week starting from the age of 2 months exhibit a slight reduced food consumption without change in water consumption and dynamics of weight gain. Their mean lifespan increases by 8% in 10% of the long-lived mice it is prolonged y 13.1% and the maximum lifespan is prolonged by 1 month. The total incidence of mammary adenocarcinoma and their multiplicity does not change under the effect of metformin, while the latency of tumor development increases and the mean diameter of tumors decreases [16224592].
Chronic treatment of inbred 129/Sv mice with metformin slightly modifies food consumption but fails to influence the dynamics of body weight, decreases by 13.4% the mean lifespan of make mice and slightly increases the mean lifespan of female mice (by 4.4%). Metformin treatment fails to influence tumor incidence in male 129/Sv mice, decreases by 3.5 times the incidence of malignant neoplasms in female mice while somehowwhat stimulate formation of benign vascualr tumors in the latter [21164223]. | Mouse | — | — | — |
| Metformin treatment | In rats metformine treatment reduces body weight significantly (despite similar food intake) but fails to significantly extend the lifespan at any quantile (25th, 50th, 75th, or 90th), overall or maximum lifespan (p > 0.05) [20304770]. | Rat | — | — | — |
| Diabenol treatment | In female NMRI and transgenic HER-2/neu mice supplementation of diabenol with drinking water 5 times a week since the age of 2 months, increases survival and inhibits spontaneous carcinogenesis.
In NMRI diabenol does not influence body weight gain dynamics, food and water consumption, but slowed down age-related disturbances in estrous function and increases the lifespan of all and 10% most long-living ones. Diabenol treatment in NMRI mice also inhibits spontaneous tumor incidence (mammary and lymphomas mainly) and increases mammary tumor latency. Diabenol treatment slows down age-related changes in estrous function in HER-2/neu mice, but fails to influence survival and slightly inhibited the incidence and decrease the size of mammary adenocarcinoma metastasis into the lung [15754958]. | Mouse | — | — | — |
| 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 | — | — | — |
GenAge
GenDR
