Factors

We need to know every factor which determines lifespan.

Lifespan factors often but not always originate from defined genetic elements. They are not just genes, by definition they can be anything for which a Classifications schema can be build for that is related to the regulation of lifespan, such entities may include Single-Nucleotide Polymorphism, transcript variants, proteins and their complexes, compounds (i.e. small molecules like metabolites and drugs), etc. A factor should be based on a defined molecular entity or genomic position and been classified. It shall be highly flexible and scalable Concept.

While individual lifespan factors within each species or precise defined molecular entities will be captured within the Lifespan App, Data Entries of the Data App may summarize for instance the relevance of each factor class (e.g. homologous group; chemical derivate of related structure and properties, etc.) as well as draw overall conclusions. o

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    Drug (8)  
  • symbol name observation species
    L-Theanine L-Theanine L-Theanine promotes paraquat resistance and extends lifespan of adult *C. elegans* [22422488].
    TSA Trichostatin A Histone deacetylase inhibitor Trichostatin A (TSA) extends the lifespan of *Drosophila melanogaster* by promoting the hsp22 gene transcription, and affecting the chromatin morphology at the locus of hsp22 gene along the polytene chromosome [15346199]. hsp70 and hsp22 RNA levels are higher in long-lived than in short-lived fly lines. The HDAC inhibitor TSA causes a higher expression of hsp22 and hsp70, and strikingly influences the lifespan in both long and short-lived lines, with variable degrees (up to 25%) [15695762]. Human
    DATS Diallyl Trisulfide DATS increases longevity apparently by enhancing skn-1. Treatment with 5-10 μM DATS increases lifespan even when treatment is started during young adulthood. DATS increases the lifespan of daf-2 and daf-16 mutants, but not that of eat-2 mutants. DATS treatment leads to the induction of the skn-1 target gene gst-4 and this induction is dependent on skn-1. DATS effect on lifespan is dependent on skn-1 activity in both intestine and ASI neurons [21296648].
    THC Tetrahydocurcumin Tetrahydocurcumin extends the lifespan and reduces oxidative stress in male and female fruit flies. THC extends lifespan of Drosophila and inhibits the oxidative stress response by regulating *FOXO* and *Sir2* [22156377]. In male mice supplementation with tetrahydrocurcumin beginning at the age of 13 month increases the mean lifespan by an average of 84 days, i.e. an increase of 11.7% [17516143]. Human
    2-MEA 2-Mercaptoethylanime hydrochloride Addition of 1% by weight 2-MEA to the diet of male LAF mice, started shortly after weaning, increases average lifespan by approximately 30%, but does not extend maximum lifespan [5723482; 11795501]. Addition of 2-MEA to the maternal diet of female mice increases the lifespan of male and female offspring by 15 and 8%, respectively [Harman & Eddy, 1979; 11795501]. Addition of 2-MEA of an antioxidant mixture containing ethoxyquin and 2-MEA to the diet of dietary restricted mice shortens lifespan approximately 20% [2394907]. References ---------------- Harman, D., and Eddy, D. E. (1979). Free radical theory of aging: beneficial effect of adding antioxidants to the maternal mouse diet on life span of offspring: possible explanation of the sex difference in longevity. Age 2, 109-22. House mouse
    2-ME 2-Mercaptoethanol Animals fed a diet supplemented with 2-mercaptoethanol (2-ME) exhibit an increased mean and maximum lifespan [6334792]. T-cell-dependent immune responses are higher in the 2-ME-fed mice compared to the controls when the animals are young. The accumulation of fluorescent products of lipid peroxidation damage is also delayed in the lymphocytes of the 2-ME-fed mice and tumor onset and incidence is reduced in these animals [6334792]. House mouse
    Diabenol 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]. House mouse
    Met Metformin In nematode 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]. In fruit fly feeding metformin to adult 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]. 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]. 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].
    CSODM Carboxyfullerene SOD mimetic Administration of a small-molecule synthetic enzyme superoxide dismutase mimetic to wild-type (i.e. non-transgenic; 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]. Carboxyfullerene SOD mimetic is an antioxidant with mitochondrial activity and nervous system penetration capability [17079053].
    C3 Tris-malonic acid derivate of the fullerene C60 molecule Tris-malonic acid derivate of the fullerene C60 molecule (C3) increases the lifespan of Sod2(-/-) mice by 300% [15451059].
    Oo Olive oil In rats oral treatment with Olive oil (at the age of 10 month for 7 months) increases mean, median and maximum lifespan by 41, 18 and 53%, respectively. Olive oil extends the lifespan with a probability of 0.99 [22498298]. In humans olive oil has positive effects on health and counteracts aging [11905662]. Its effect is suggested to be a function of the dose [19369055]. Fruit fly
    C60 [60]fullerene Oral administration of C60 dissolved in olive oil (0.8 mg/ml) at reiterated doses (1.7 mg/kg of body weight) for just about 7 months to rats not only does not entail chronic toxicity but it almost doubles the lifespan. The effects on lifespan is mainly due to the attenuation of age-associated increases in oxidative stress. Dissolved C60 is absorbed by the gastro-intestinal tract and eliminated in a few tens of hours [22498298]. C60-olive oil can increase the mean, median and maximum lifespan by 114, 91 and 74%. C60-olive oil extends the lifespan of animals with a probability of 0.999 and 0.995 with respect to water and olive oil treatments, respectively [22498298]. The GSSG/GSH ratio of animals treated by C60-olive oil is significantly less (about twice as less) as compared to controls [22498298]. C60 solutions have a characteristic purple color. C60 can cross the blood-brain barrier [21787853]. The elimination process follows a non-urinary route as it is mainly eliminated through the bile ducts [16351219; 21787853]. C60 reacts inside the liver cells with vitamin A following a Diels-Alder like reaction both in mice and rats [16351219].
    Mincoycline In Drosophila melongaster treatment with minocycline (0.87mM) prolongs mean, median and maximum lifespan of wild-type (Oregon strain) of both genders. In females mincocycline extend mean and maximum lifespan by 57 and 78%, respectively. In males minocycline results in a mean and maximum lifespan extension by 114 and 28%, respectively [23185716].
    DDS 4,4'-diaminodiphenylsulfone In nematode treatment with DDS extends the lifespan [20974969]. DDS causes the delay of aging and decreases the level of a mitochondrial complex as well as lowers oxygen consumption and enhances oxidative stress resistance [20974969]. Pyruvate kinase is bound and inhibited by DDS in vitro and in vivo [20974969]. Hansen disease patients in Korea, who usually have taken DDS for several decades, have a longer lifespan in spite of their socioeconomic disadvantages [19084552]. House mouse
    NAS N-acetyl-serotonin N-acetyl-serotonin (a melatonin precursor) administrated in mice with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771].
    MEL Melatonin Melatonin administrated to mice with drinking water increases anti-oxidant capacity of the brain and prolongs the mean lifespan by 20% of males but not females [11462771].
    Res Resveratrol Resveratrol significantly extends the lifespan of yeast [12939617]. Resveratrol supplementation prolongs the lifespan of nematodes [15254550; 17460219], but not in any case [17875315]. In fruit flies supplementation with resveratrol extends the lifespan [15254550], but not in always [17875315]. In Nothobranchius furzeri a maximum dose of resveratrol increases the median lifespan by 56% [16461283]. 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 range a 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].
    Laz Lazarillo Extracellular forms of Laz have autocrine and paracrine protecting effects for oxidative stress-challanged Drosophila S2 cells. Local effects of GPI-linked Laz inside and outside the nervous system promote survival upon different stress forms, and extend lifespan and healthspan of the flies in a cell-type dependent manner. Ectopic enhancement of Laz expression increases mean, median, and maximum lifespan. Laz overexpression (via the use of a ubiquitous da-GAL4 driver) increases median lifepan by 28.3% (p < 0.0005). Overexpression of Laz specifically in muscles and brain (via GAL4109(2)80 driver) increases median lifespan by 43.5%. Laz overxpression in dopaminergic and serotenergic neurons and epidermis increases median lifespan bt 31.4% (p < 0.0005) [22846641]. Fruit fly
    DCI D-chiro-inositol In fruit flies, 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].
    Pinitol In fruit flies, 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].
    CS Cynomorium songaricum In fruit fly, the yang-tonifying herbal medicine cynomorium songaricum Repr. (CS) supplementation to the diet extends both the mean and the maximum lifespan of adult females, but insignificantly that of males. In females, maximum lifespan (determined by the 90th survival percentile) is increased by up to 11.4% with 10 mg/mL CS and 5.7% with both 20 and 30 mg/mL Cs. Mean lifespan is significantly extended by 15, 18 and 11% upon treatment with 10, 20, and 30 mg/mL CS, respectively (all P <0.001). Increased lifespan by CS is correlated with higher resistance to oxidative stress and starvation and lower lipid hydroxyperoxids levels as well as accompanied by beneficial effects, such as improved mating readiness, increased fecundity, and suppresion of age-related learning impairment in aged animals [22844336].
    Tyrosol In nematodes treatment with tyrosol (250 microMolar) extends mean, median, and maximum, lifespan by 21, 21, and 11% [22824366].
    Spd Spermidine Administration of spermidine extends lifespan of yeast, flies and worms and human immune cells. In yeast spermidine treatment triggers deacetylation of H3 through inhibition of histone acetylatranserfases, suppresses oxidative stress and necrosis. Altered acetylation of the chromatin results in upregulation of various autophagy-related genes and triggers autophagy [19801973]. In nematodes treatment with 0.2 mM spermidine extends mean and maximum lifespan of wild-type by 16 and 13% significantly (<0.005) as well as the mean and maximum lifespan in sir-2.1(ok434) by 12 and 11% significantly (<0.01).
    TRE Trehalose In nematodes treatment with trehalose starting from the young-adult stage extends the mean lifespan by over 30% without any side effects. Trehalose treatment starting even from the old-adult stage shortly thereafter retards the age-associated decline in survivorship and extends the remaining lifespan by 60%. Lifespan extension by trehalose lowers the age-independent vulnerability. Trehalose increases reproductive span and retards the age-associated decrease in pharyngeal-pumping rate and the accumulation of lipofuscin autofluorescence as well as enhances thermotolerance and reduces polyglutamine. The lifespan extending effect of trehalose is abolished in daf-2 mutants [20477758]. Trehalose is suggested to act as a stress protectant against heat, cold, desiccation, anoxia, and oxidation [20477758]. 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].
    Beau I beauveriolide I In budding yeast treatment with beauveriolide I (20 microgram/mL) extends chronological lifespan in BY4741 by around 50% [22790951].
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    • 25 of 55 factors
    Factors are an extension of GenAge and GenDR.

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