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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  • symbol name observation species
    Chromosome 4 epithelial cell adhesion molecule Human
    IL6 interleukin 6 (interferon, beta 2) Human
    Mir669c microRNA 669c Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging [18561983]. House mouse
    miR-214 microRNA 214 Expression increases with age in mouse liver. The miRNA downregulates detoxification and regeneration genes, which may contribute to aging [18561983]. House mouse
    Mir34a microRNA mir-34a Increases in aging rat liver, which suppresses the expression of such proteins as Sirt1 and Mgst1, resulting in dysfunction of oxidative stress defense and regulation [21216258] Norway rat
    Mir93 microRNA mir-93 Increases in Aging rat Liver, which suppresses the expression of such proteins as Sirt1 and Mgst1, resulting in dysfunction of oxidative stress defense and regulation [21216258] Norway rat
    Mir27a MicroRNA 27a In Ames dwarf mice (which displays delayed Aging), Mir27a expression is significantly higher than in control mice. Mir27a may be responsible for delayed Aging in dwarf mice: it suppresses the expression of ODC1 and SRM, which in turn suppresses polyamine synthesis in dwarf mice liver. Part of the ability of dwarf mice to suppress or avoid tumor or Cancer growth may be attributed to the decreased Polyamine biosynthesis. [19878148] House mouse
    H2S Hydrogen Sulfide Hydrogen sulfide (H2S) is a colorless, poisonousness, flammable gas with the characteristic foul odor of rotten eggs. A few breath of air containing high levels H2S can cause death, while lower long-term exposure can cause eye irritation, headache, and fatigue. The human body produces small amounts of hydrogen sulfide and uses it as signaling molecule. It has a variety of physiological effects. For instance, it relaxes the vascular endothelium and smooth muscle cells, which is important to maintaining clean arteries as one ages. It is an important signaling molecule because of its significant effects on the cardiovascular and nervous systems. Hydrogen sulfide appears to slow aging by inhibiting free-radical reactions via the activation of SIRT1 and probably through its Interactions with Klotho. Klotho seems to be upregulated by hydrogen sulfide and extends lifespan via a number of different pathways, some of which promote production of endogenous antioxidants. H2S produced in the kidneys has direct angiotension-converting enzyme (ACE) inhibiting activity. It is therefore an ACE inhibitor, just like certain drugs that mitigate high blood pressure. Plasma hydrogen sulfide declines with age and is lower in spontaneously hypertensive rats. A lack of hydrogen peroxide is in general implicated in cardiovascular disease. Declining hydrogen sulfide levels also underline neurological health. Endogenous hydrogen sulfide is lower in animal model of Parkinson disease and depressed in the brains of patients with Alzheimer's disease. Hydrogen sulfide may also protective in animal models as well as humans against cancer [23297346].
    EXO1 exonuclease 1 The rs1776180 C allele in the promoter of EXO1 is significantly enriched in female Germans centenarians and this can be replicated in 445 female French centenarians. The C allele leads to the loss of binding site for the basic helix-loop-helix transcription factor E47, resulting in higher EXO1 expression [19698732].EXO1 was found to be associated with longevity [19698732]. EXO1 was not found to be associated with longevity [23770741]. Human
    tert telomerase reverse transcriptase First-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescence cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is rescued in tp53(-/-)tert(-/-) mutants, underscoring p53 as mediator of telomerase deficiency and consequent telomere instability [http://denigma.de/url/3p]. Zebrafish
    GH1 Growth hormone 1 Transgenic mice overexpressing bovine GH1 are bigger than controls and display early onset of pathological changes in the kidneys such glomerulosis and glomerulonephritis as well as signs of premature aging such as a shortened lifespan, increased astrogliosis, shortened reproductive lifepsan and early onset of age-related changes in cognitive function, hypothalamic neurotransmitter turnover, and plasma corticosterone levels [14583653]. Cattle
    Germline Sterilization prolongs lifespan, in species from insect to humans. In hermaphrodite C. elegans, removing sperm and egg-producing cells extends lifespan by 50%. Removing those cells triggers a reaction in the surrounding tissue. The signal is send out in the form of a steroid hormone, that turns on a molecular switch, which switches them into a kind of survival mode. Specifically, remaining gonadal cells trigger production of a steroid hormone dafachronic acid. Dafachronic acid activates miRNAs, which work as tiny molecular switch causing changes in gene expression that promote longevity. The same steroid hormone-miRNA switch is part of the developmental clock. The loss of the germ cells ultimately causes the worm to use developmental timers to put in motion a lifespan-prolonging programme [23239738].
    CCL2 chemokine (C-C motif) ligand 2 CCL2 levels in plasma increase with age and it is part of the senescence-associated secretory phenotype [19648977]. Human
    CCL2 chemokine (C-C motif) ligand 2 CCL2 levels are evaluated in old unpaired and young heterochronic (with old animals) paired mice [21886162]. House mouse
    CCL11 chemokine (C-C motif) ligand 11 CCL11 exhibits an age-related increase in the plasma and cerebrospinal fluid from healthy human individuals between 20 and 90 years [21886162]. Human
    CCL11 chemokine (C-C motif) ligand 11 CCL11 is an age-related systemic factor associated with decreased neurogenesis. Relative levels of CCL11 increase in the plasma during aging an in young mice during Heterochronic Parabiosis [21886162]. House mouse
    BUB1B budding uninhibited by benzimidazoles 1 homolog beta (yeast) Mutations in BUB1B are associated with mosaic variegated aneuplody, a rare human syndrome characterized by aneuplodization, tumour predisposition and several progeroid traits, including short lifespan, growth and mental retardation, cataracts and facial dysmorphisms [16411201; 15475955; 20651707]. Human
    MIR21 MIRN21; hsa-mir-21; miR-21; miRNA21 MIR21 is the most highly expressed microRNA gene in octogenarians and centenarians. MIR21 expression is higher under cardiovascular diseases and lower in centenarian offspring. MIR21 is correlated with C-reactive protein and fibrinogen levels. TGF-βR2 mRNA, a MIR21 target, exhibits the highest expression in leukocytes form a subset of octogenarians. MIR-21 may be a biomarker of inflammation [23041385]. Human
    ELOVL2 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 2 In breast, kidney and lung tissues the makers cg23606718 and cg16867657 were commonly differentially methylated with age and both have been annotated to ELOVL2 [23177740], which is linked to photoaging response in human skin [20514327]. Human
    GTPBP10 GTP-binding protein 10 (putative) Age-related differential methylation of the genetic marker rs42663, which is missense mutation in GTPBP10 is statistically significant association with age and aging rate. GTPB10 associates with cg27367526 in STEAP2 [23177740]. Human
    JAKMIP3 Janus kinase and microtubule interacting protein 3 Age-related differential methylation of the genetic marker rs2818384 which is synonymous to the mutation in JAKMIP3 is statistically significant association with age and aging rate. JAKMIP3 has a *cis* association with the aging differential methylated marker cg05652533 [23177740]. Copy-number variants of JAKMIP3 are associated with glioblastoma [Xiong et al. 2010]. Xiong, M., Dong, H., Siu, H., Peng, G., Wang, Y., and Jin, L. (2010). Genome-Wide Association Studies of Copy Number Variation in Glioblastoma. Proceedings of the 4th International Conference on Bioinformatics and Biomedical Engineering (iCBBE), 1–4. Human
    NEK4 NIMA (never in mitosis gene a)-related kinase 4 Age-related differential methylation of the genetic marker rs2230534 which is synonymous to the mutation in NEK4 is statistically significant association with age and aging rate [23177740]. Human
    KLF14 Kruppel-like factor 14 Six aging differentially methylated markers lay within KLF14 [23177740]. Human
    SST Somastatin Two with age-related differential methylation markers lay within Somastatin (SST) [23177740] which declines with age and is linked to Alzheimer's disease [15778722]. Human
    MDB4 methyl-CpG binding domain protein 4 Methylation marker cg27193080 is significantly associated with age and its methylation fraction is influenced by the SNP variantrs140692. Both the SNP and the methylation marker map to the MBD4, with the SNP in an intron and the methylation marker just upstream of the coding region [23177740]. Human
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    • 25 of 99 factors
    Factors are an extension of GenAge and GenDR.

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