Skip to main content
. 2020 Oct 8;19(11):e13256. doi: 10.1111/acel.13256

Table 1.

20 examples of common aging plasma proteins with highly intriguing links to aging and/or disease

Protein q‐value, age coefficient Intriguing connections to aging and/or disease
ADAMTS5 7.69E−65, 1.88E−03

  • Mice lacking Adamts5 are protected from cartilage destruction following joint instability induced by surgery (Glasson et al., 2005)

  • ADAMTS5 is overexpressed in osteoarthritic cartilage from mice and humans (Lin et al., 2009)

  • Wwp2 promotes the maintenance of cartilage homeostasis via the suppression of Adamts5 in mice (Mokuda et al., 2019)
BDNF 2.78E−30, 2.84E−03

  • Treating Huntington's disease mice with human mesenchymal stem cells that overexpress BDNF extends life span and increases neurogenesis‐like activity (Pollock et al., 2016)

  • Exercise elevates BDNF levels and induces adult hippocampal neurogenesis in Alzheimer's disease mice (S. H. Choi et al., 2018)

  • In a zebrafish model of Alzheimer's disease, BDNF enhances neurogenesis and neural stem cell plasticity (Bhattarai et al., 2020)
CCL11 8.87E−94, 3.34E−03

  • In a cohort of non‐diabetic women, plasma levels of CCL11 are associated with central obesity and are reduced in response to an exercise program (Choi et al., 2007)

  • Injecting recombinant Ccl11 into young mice reduces neurogenesis and impairs both memory and learning (Villeda et al., 2011)

  • Administering recombinant Ccl11 to young mice results in synaptic loss and increased microglial reactivity (Das et al., 2019)
CGA.FSHB 2.89E−320, 1.64E−02

  • Long‐lived mice deficient in growth hormone receptor exhibit decreased plasma levels of follicle‐stimulating hormone (V. Chandrashekar et al., 2007)

  • Bone loss is mitigated in ovariectomized mice treated with an antibody specific to the β‐subunit of follicle‐stimulating hormone (Zhu et al., 2012)

  • An antibody specific to the β‐subunit of follicle‐stimulating hormone decreases body fat, stimulates brown adipose tissue, and promotes thermogenesis in mice (Liu et al., 2017)
FGA.FGB.FGG 8.38E−11, 7.25E−04

  • Treating mice with fibrinogen causes demyelination via the induction of adaptive immune responses and the recruitment of peripheral macrophages (Ryu et al., 2015)

  • Inhibiting fibrin with the monoclonal antibody 5B8 attenuates neurodegeneration and innate immunity in mouse models of multiple sclerosis and Alzheimer's disease (Ryu et al., 2018)

  • In Alzheimer's disease mice, genetically deleting a binding motif in fibrinogen reduces neuroinflammation and cognitive decline (Merlini et al., 2019)
IL15RA 1.31E−43, 1.57E−03

  • Mice lacking Il15ra have a higher body temperature, consume more oxygen, and are leaner despite increased food intake (He et al., 2010)

  • Fast skeletal muscles in Il15ra −/− mice are more resistant to fatigue and have a greater exercise capacity (Pistilli et al., 2011)

  • Il15ra −/− mice are protected from diet‐induced obesity and exhibit enhanced fatty acid oxidation (Loro et al., 2015)
IL6 4.13E−05, 7.16E−04

  • The ability to ward off bacterial or viral infection is impaired in Il6 knockout mice (Kopf et al., 1994)

  • Genetically disrupting Il6 in mice impairs liver regeneration and causes liver failure (Cressman et al., 1996)

  • Transgenic mice overexpressing human IL6 are substantially smaller and have reduced levels of circulating Igf1 (De Benedetti et al., 1997)
LIFR 5.43E−08, −6.27E−04

  • Increasing the expression of LIFR in malignant cells suppresses tumor metastasis in mice (D. Chen et al., 2012)

  • Inoculating mice with breast cancer cells lacking LIFR promotes bone destruction (R. W. Johnson et al., 2016)

  • Mouse Lifr contains separate protein domains that either maintain stem cell self‐renewal or induce differentiation (X. J. Wang et al., 2017)
LILRB2 9.22E−21, 1.07E−03

  • The genetic deletion of Lilrb3 (mouse ortholog of human LILRB2) protects mice from Aβ‐induced memory impairment (Kim et al., 2013)

  • Small molecule inhibitors targeting the binding site of LILRB2 disrupt LILRB2‐Aβ interactions and reduce Aβ cytotoxicity (Cao et al., 2018)

  • The anti‐tumor effects of T‐cell immune checkpoint inhibitors are enhanced by the blockade of LILRB2 (Chen et al., 2018)
MMP12 2.53E−92, 3.64E−03

  • A single nucleotide polymorphism in MMP12 is associated with a reduced risk of chronic obstructive pulmonary disease (Hunninghake et al., 2009)

  • Large artery atherosclerosis is associated with a genetic variant in the MMP12 locus and this gene is overexpressed in carotid plaques (Traylor et al., 2014)

  • In mice deficient in Ldlr, the deletion of Mmp12 protects male mice from both arterial stiffness and atherosclerosis (Liu et al., 2019)
NAB1 1.14E−26, −2.01E−03

  • NAB1 is upregulated in human heart failure and mice overexpressing Nab1 are protected from induced hypertrophy (Buitrago et al., 2005)

  • In dogs with moderate heart failure, treatment with rosuvastatin reduces the expression of NAB1 in left ventricular tissue (Zaca et al., 2012)

  • A single nucleotide polymorphism in NAB1 is associated with systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and idiopathic inflammatory myopathies (Acosta‐Herrera et al., 2019)
NTN1 2.09E−50, 2.32E−03

  • Overexpressing Ntn1 in the mouse gut suppresses intestinal cell apoptosis and promotes tumor development (Mazelin et al., 2004)

  • In mice lacking the low‐density lipoprotein receptor, deleting Ntn1 in macrophages attenuates atherosclerosis (van Gils et al., 2012)

  • In a mouse model of obesity, the hematopoietic deletion of Ntn1 enhances insulin sensitivity and decreases inflammation (Ramkhelawon et al., 2014)
PAK4 2.47E−04, 9.28E−04

  • Knocking down PAK4 in ovarian cancer cells prior to inoculation impedes tumor growth and dissemination in nude mice (Siu et al., 2010)

  • Overexpressing or depleting Pak4 in mice promotes or delays mammary cancer, respectively (Costa et al., 2019)

  • Growth is suppressed and invasive potential is decreased by the inhibition of PAK4 in human bladder cancer cells (D. S. Chandrashekar et al., 2020)
PLA2G2A 1.56E−03, 7.11E−04

  • The size and multiplicity of intestinal tumors are reduced in mice overexpressing Pla2g2a (Cormier et al., 1997)

  • The expression of PLA2G2A is positively correlated with survival in patients with gastric adenocarcinoma (Leung et al., 2002)

  • In Muc2 −/− mice, the transgenic expression of Pla2g2a suppresses intestinal tumorigenesis (Fijneman et al., 2008)
PLXNB2 9.33E−40, 1.17E−03

  • Inhibiting PLXNB2 suppresses the development of xenograft tumors in mice (Yu et al., 2017)

  • Inhibiting PLXNB2 makes prostate cancer stem cells more sensitive to chemotherapy (Li et al., 2020)

  • Motor sensory recovery following spinal cord injury is impaired in mice lacking Plxnb2 in myeloid cells (X. Zhou et al., 2020)
POMC 1.53E−07, 9.34E−04

  • Mutations in POMC cause early‐onset obesity and adrenal insufficiency in humans (Krude et al., 1998)

  • Blocking the expression of Pomc in hypothalamic neurons causes hyperphagia and obesity in mice (Bumaschny et al., 2012)

  • In obese patients with defects in POMC, treatment with a melanocortin‐4 receptor agonist reduces hunger and induces weight loss (Kuhnen et al., 2016)
PRKAA1.PRKAB1.PRKAG1 4.11E−02, 3.24E−04

  • Worms constitutively expressing aakg‐2 (worm ortholog of PRKAG1) are more resistant to oxidative stress and live longer (Greer et al., 2007)

  • Ampk elevates cellular NAD+ levels and enhances the activity of Sirt1 in mouse skeletal muscle (Canto et al., 2009)

  • Overexpressing AMPKα (fly ortholog of PRKAA1) in neurons induces autophagy and extends life span in Drosophila (Ulgherait et al., 2014)
RBM3 6.61E−20, 2.21E−03

  • Cold stress increases the expression level of RBM3 in multiple different human cell lines (Danno et al., 1997)

  • Overexpressing Rbm3 prevents neuronal loss and prolongs survival in Alzheimer's disease mice (Peretti et al., 2015)

  • In response to hypoxic ischemia, Rbm3 promotes the proliferation of neural stem/progenitor cells in the subgranular zone (X. Zhu et al., 2019)
SIRT5 9.61E−10, 8.53E−04

  • Creating a Sirt5 deficiency in Parkinson's disease mice exacerbates motor deficits and dopaminergic degeneration (Liu et al., 2015)

  • Knocking out Sirt5 in mice leads to the development of hypertrophic cardiomyopathy (Sadhukhan et al., 2016)

  • Mice deficient in Sirt5 exhibit cold intolerance and a reduced browning capacity in white adipose tissue (Shuai et al., 2019)
UFM1 2.51E−03, 5.82E−04

  • Deletion mutations that affect the ufm‐1 cascade result in reduced fecundity and life span in worms (Hertel et al., 2013)

  • RNAi knockdown against Ufm1 decreases life span and causes locomotive defects in fruit flies (Duan et al., 2016)

  • A homozygous mutation in UFM1 causes early‐onset encephalopathy with progressive microcephaly in humans (Nahorski et al., 2018)

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 three relevant connections to aging and/or disease are provided.