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
    ttll-9 Tubulin Tyrosine Ligase Like Knockdown of ttll-9 throughout the entire life increases the lifespan by 3% [23698443]. Nematode
    RPL6A Ribosomal Protein of the Large subunit 6A Deletion of RPL6A decrease mean replicative lifespan by 25% in the alpha strain [18340043; 18423200], but increases mean replicative lifespan by 40% in the remade strain. Its deletion non-significantly increases mean replicative lifespan in the ORF collection [22377630]. Budding yeast
    PMR1 High affinity Ca2+/Mn2+ P-type ATPase required for Ca2+ and Mn2+ transport into Golgi; involved in Ca2+ dependent protein sorting and processing; mutations in human homolog ATP2C1 cause acantholytic skin condition Hailey-Hailey disease Deletion of PMR1 increses the replicative lifespan by 40% in the alpha strain and by 15% in the a strain. Overexpression of PMR1 extends the lifespan [21918615]. Budding yeast
    NDE1 NADH Dehydrogenase, External 1 Overexpression of NDE1 and NDE2 increases intracellular NAD/NADH ratio by lowering NADH concentration and increases replicative lifespan by 20-25%. This lifespan extension is non-additive 0.5% glucose restriction [14724176]. Deletion of NDE1 extends chronological lifespan [16436509]. Budding yeast
    old-1 Overexpression Longevity Determinant Overexpression of old-1 in transgenic animals increases mean and maximum lifespan by 40-100% (average 65%) and 97%, respectively. old-1 overexpression of increases stress resistance (to heat by 20% and ultraviolet irradiation by 33%) without altering development or fertility. Effects of old-1 on lifespan and stress resistance is under regulation of daf-16 [9768365]. old-1 mRNA levels are upregulated in response to stress and in daf-2 as well as age-1 mutant backgrounds [11591319]. old-1 expression is downregulated in daf-2 mutants [12845331]. old-1 RNAi in an rrf-3 mutant background slightly extends lifespan [12845331]. old-1 is expressed in the anterior region of the worm, in neuronal, hypodermal and pharyngeal tissues as well in the proximal region in the male gonad. Its expression is detectable in young adults and appears to increase as animals age and in response to heat, starvation, or UV irradiation. Nematode
    SSD1 Suppressor of SIT4 Deletion 1 Overexpression of SSD1 (addition of a SSD1-V allele) increases replicative lifespan by 50%, independently of SIR2 and SIR2 further extends the lifespan, although SIR2 is necessary for SSD1-V cells to attain maximal lifespan [15126388]. SSD1-V also dramatically increases chronological lifespan with lifespan twice as long as ssd1-d cells [19570907]. Deletion of SSD1 increases replicative lifespan by 50% [Li et al., 2009]. Addition of SSD1-V allele to an ssd1-d strain suppresses the short lifespan of an MPT5 deletion mutant [11805047] and extend wild-type lifespan [Kaeberlein and Guarente, unpublished]. SSD1-V slightly extends the lifespan of swi4 and ccr4 mutant strains and suppresses the temperature sensitive growth phenotype of mpt5, ccr3, swi4, and swi6 single mutants [11805047]. SSD1-V also suppresses the synthetic lethality caused by deletion of MPT5 in combination with a mutation in SWI4, SWI6, or CCR4 [11805047]. SSD1-V suppresses mutations that affect cell wall stability [1545797; 8386319], RNA polymerase III activity [8510644], RNA splicing [10446233], and PKA activity [1848673; 8200529]. Budding yeast
    ins-1 INSulin related Increased dosage of ins-1 under its own promoter as well as a heat shock promoter increases lifespan by 25% and is also able to increase the lifespan of daf-2 mutants [11274053]. ins-1 RNAi increases lifespan by 20%. ins-1 is differentially transcribed in daf-16 and daf-2 animals [12845331]. Overexpression of ins-1 also causes an increase in dauer formation and can enhance the dauer formation of daf-2 mutants [11274053]. Nematode
    • 7 factors
    Factors are an extension of GenAge and GenDR.

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