mSALT: mammalian Signatures of Aging and Longevity Traits

mSALT is a platform for investigation of associations between mammalian gene expression and traits of aging and longevity within and across species.

To cite the use of this app in your publications, please reference:
Tyshkovskiy A, Ma S, Shindyapina AV, Tikhonov S, Lee SG, Bozaykut P, Castro JP, Seluanov A, Schork NJ, Gorbunova V, Dmitriev SE, Miller RA, Gladyshev VN (2023). Distinct longevity mechanisms across and within species and their association with aging. Cell. 2023;186(13):2929-2949.e20. doi:10.1016/j.cell.2023.05.002

mSALT includes three instruments to visualize longevity and aging associations:

1. Summary barplot

This instrument allows to investigate how expression of individual genes is associated with various signatures of (i) aging, (ii) maximum lifespan across species and (iii) lifespan extension in mice. For every gene of interest, it demonstrates aggregated normalized slope coefficient or log fold change (logFC), which reflects the direction and size of association with the corresponding signature. Red asterisk denotes if the signature exhibits significant association with the expression of chosen gene.

The description of all shown signatures is provided below:

Species: Brain ML, Kidney ML and Liver ML - the association between maximum lifespan (ML) of mammalian species and gene expression in brain, kidney and liver, respectively;
Species: Brain MLres, Kidney MLres and Liver MLres - the association between maximum lifespan adjusted for adult body weight (MLres) of mammalian species and gene expression in brain, kidney and liver, respectively;
Interventions: Median lifespan and Maximum lifespan - the association between the size of intervention lifespan-extending effect on mouse median and maximum lifespan, respectively, and gene expression in liver;
Interventions: CR, GH deficiency and Rapamycin - the effect of caloric restriction (CR), growth-hormone (GH) deficiency (including Ames dwarf, Snell dwarf, Laron and Little mice) and rapamycin, respectively, on gene expression in mouse liver;
Interventions: Common - the effect of various longevity interventions in mice on gene expression in liver;
Aging: Brain, Muscle and Liver - the association of gene expression in brain, muscle and liver, respectively, with aging across humans, rats and mice (multi-species signatures);
Aging: Human, Rat and Mouse - the association of gene expression in humans, rats and mice, respectively, with aging across 17 various tissues (multi-tissue signatures);
Aging: Global - the association of gene expression across humans, rats and mice across 17 various tissues (multi-species multi-tissue signature).

The following options are available for this tool:

Display signatures: defines if gene expression association should be demonstrated for signatures of long-lived species (expression in various organs of mammals vs their maximum lifespan), lifespan-extending interventions (expression in liver of mice subjected to longevity interventions vs lifespan-extending effect) or aging (age-related gene expression changes in various organs of human, mouse and rat).
Adjusted p-value threshold (default: 0.05): sets threshold for Benjamini-Hochberg adjusted p-value corresponding to the null hypothesis that expression of a certain gene has neither positive nor negative association with the corresponding signature (its slope/logFC is equal to 0). Red asterisk denotes signatures with adjusted p-value < current threshold.

2. Long-lived species

A. Association with lifespan across species

This instrument demonstrates how normalized gene expression is associated with maximum lifespan or female time to maturity (in log scale) across 41 mammalian species. Each dot represents mean expression of the chosen gene for a single species, and errorbars are standard errors (SE).

The following options are available for this tool:

Tissue: defines the tissue where gene expression is measured for each species.
Trait: defines the longevity trait of interest. Options include maximum lifespan (ML), maximum lifespan adjusted for adult body weight of the species (MLres), female time to maturity (FTM), and female time to maturity adjusted for adult body weight of the species (FTMres). All specified traits are displayed in log scale.
Draw regression line: specifies if the regression line demonstrating the association between gene expression and longevity trait should be added. Possible options for regression model include simple linear regression model (Linear) and phylogenetic regression model, which adjusts for evolutionary relationships between analyzed species (Phylogenetic). The corresponding regression equation and R squared can be added via Add regression equation option.
Color samples by: defines if individual points should be colored based on taxonomic order of the species (Order) or source of the data (GEO ID) (Source).

3. Lifespan-extending interventions

A. Effect of individual interventions

This instrument demonstrates the aggregated expression fold change (logFC) for a particular gene in mouse liver in response to different lifespan- and healthspan-extending interventions. Red asterisk denotes interventions, which significantly affect the expression of the chosen gene.

The following options are available for this tool:

Only significant longevity effect: defines if the barplot should include datasets corresponding to all treatments (No) or only interventions and experimental conditions, which have been shown to produce statistically significant extension of lifespan in Mus musculus model (Yes).
Adjusted p-value threshold (default: 0.05): sets threshold for Benjamini-Hochberg adjusted p-value corresponding to the null hypothesis that expression of a certain gene is neither up- nor downregulated in response to a corresponding intervention (its aggregated logFC is equal to 0). Red asterisk denotes interventions with adjusted p-value < current threshold.

B. Association with lifespan extension effect

This instrument allows to discover positive or negative associations between hepatic expression change of individual gene and the effect of longevity interventions on mouse lifespan. Each dot corresponds to a single dataset and represents mean logFC of the gene in response to a particular treatment. Errorbars are standard errors (SE).

The following options are available for this tool:

Trait: defines the quantitative metric shown on the x-axis. Available estimates for the size of lifespan extension effect include change of Maximum lifespan (log ratio of average lifespans of 10% most long-lived animals in the intervention and control cohorts) and Median lifespan (logarithm of ratio between median lifespans in the intervention and control cohorts). All values are obtained from published survival data for Mus musculus model.
Only significant longevity effect: defines if plot should include datasets corresponding to all treatments (No) or only interventions and experimental conditions, which have been shown to produce statistically significant extension of lifespan in Mus musculus model (Yes).
Subset by sex: defines if datasets corresponding to Both sexes, Only males or Only females should be included.
Color samples by: defines if individual points should be colored based on Type of intervention, Source (Pubmed ID) or Sex.
Draw regression line: specifies if the linear regression line corresponding to the association between gene expression and lifespan extension effect should be added (Linear). The corresponding regression equation and R squared can be added via Add regression equation option.
Shape samples by: defines if individual points should be shaped based on Sex.