Table 2.
Examples of common aging plasma proteins that can significantly extend life span in a vertebrate animal model when manipulated
| Protein | q‐value, age coefficient | Life span effect |
|---|---|---|
| AKT2 | 1.61E−16, 1.04E−03 | Mice deficient in Akt2 display a 9.1% increase in median survival and an improvement in myocardial contractile function (Ren et al., 2017) |
| GDF11 | 1.92E−02, −7.20E−04 | In killifish, levels of gdf11 decrease with age and treating aged animals with recombinant gdf11 lengthens mean life span by 8.3% (Zhou et al., 2019) |
| GDF15 | 1.71E−249, 5.26E−03 | The overexpression of human GDF15 in female mice extends median life span (19.5% for transgenic line 1377 and 12.9% for transgenic line 1398) and protects against weight gain and insulin insensitivity (Wang et al., 2014) |
| GHR | 7.56E−24, −1.53E−03 | Ghr −/− mice live longer (8.7%–28.2% increase in median life span depending on the sex and mouse strain), weigh less, and exhibit reduced levels of fasting glucose and insulin (Coschigano et al., 2003) |
| NAMPT | 5.39E−04, 1.12E−03 | Wheel‐running activity is enhanced and longevity is boosted (10.2% increase in median life span) in aged female mice treated with extracellular vesicles containing Nampt (Yoshida et al., 2019) |
| PAPPA | 9.29E−05, 8.09E−04 | The incidence of spontaneous tumors is reduced and life is prolonged (37.5% increase in mean life span) in mice lacking Pappa (Conover & Bale, 2007) |
| PLAU | 6.46E−11, 8.67E−04 | Overexpressing Plau in mice elongates median life span (36%, 16%, and 23% for 75th, 50th, and 25th percentile survivors, respectively), reduces food intake, and decreases body weight (Miskin & Masos, 1997) |
| PTEN | 2.41E−02, 4.06E−04 | Longevity is enhanced (12.4% increase in median life span), cancer incidence is decreased, and insulin sensitivity is improved in mice harboring additional copies of Pten (Ortega‐Molina et al., 2012) |
| SHC1 a | 7.18E−04, 8.53E−04 | Median life span is extended by 27.9% and oxidative stress resistance is enhanced in Shc1 −/− mice (Migliaccio et al., 1999) |
For each protein, the q‐value and age coefficient (measured in a human proteomic dataset derived from 4263 individuals aged 18–95 years) as well as the life span effect are included. Bolded words and numbers highlight the lifespan effect in response to a given intervention.
a
A follow‐up study assessed life span in Shc1 knockout mice at two different locations. At one location, Shc1 −/− mice on a 40% calorie restriction diet exhibited a survival benefit (median 70th percentile survival was increased by 8%). At the other site, no longevity benefit was observed in Shc1 knockout mice fed ad libitum (Ramsey et al., 2014).