Table 1.

Common and tissue-specific changes in the healthy aging endothelium transcriptome landscape

	Transcriptional changes (up) ↑	Transcriptional changes (down) ↓	EC population changes	EC Turnover	Possible functional consequences	References
Brain	Signatures of: Angiogenesis, ECM organization, Glycolysis, Hypoxia, Inflammation, IFN-signaling, Krüppel-like factors, Oxidative stress, Proteostasis, Vasoprotection Transcriptional noise Vwf expression	Signatures of: Glycolysis and energy metabolism, cell–cell junctions Slc38a5 expression Aplnr expression	Mixed findings: either no change in EC subtype abundance, or a loss of capillary-venous ECs Slight increase in number of ECs with senescence signature Capillary ECs most susceptible to aging-associated DEGs	X	Increased BBB permeability Reduced blood flow Neuronal death	[16, 26–31, 39, 43, 123]
FRS	Signatures of: Angiogenesis (VEGF), Apoptosis, Cell cycle, Cellular survival, Immunoregulation, Senescence, Stress response SOX TF activity	Signatures of: DNA repair, Proteasome, Metabolism RGCC expression Cross-talk (Angiogenic, (HGF, ANGPTL, EDN)	FLNA + ACTG2 + Contractile EC population Potential decrease of capillary clusters Decrease in vascular and lymphatic ECs		Hampered blood flow and vascularization	[39, 97–100]
Heart	Signatures of: Atherosclerosis, Neuronal impairment (Sema3a), Senescence IL7 expression Transcriptional noise	Signatures of: Angiogenesis, ECM organization FOXO3A expression	Decreased abundance of capillary clusters Strong susceptibility to aging (coronary artery EC and capillary EC)	✓	Sympathetic denervation Potential reduction of vascular homeostasis and repair	[39, 73, 80–84, 127]
Kidney	Signatures of: Inflammation, IFN-signaling, Senescence (esp. glomerular ECs)		Decreased abundance of capillary clusters Glomerular ECs susceptible to aging-associated DEGs		Renal dysfunction, kidney disease	[39, 72, 80, 110, 136]
Lung	Signatures of: Inflammation, IFN-signaling, Senescence Expression of: Vwf, NFKB1, HIF1A, IL7, Il1b Cross-talk (ECs & immune cells) Transcriptional noise	Apln expression	Aging-associated changes mostly detected in capillaries	✓ (general capillary ECs)	Potential impairment of vascular repair after injury (IPF, COPD, COVID-19)	[67, 70–74, 77]
Muscle	Signatures of: Inflammation Immunoregulation (Rfx5, Nfat5)	Circadian rhythm regulation Angiogenic signatures	Increased abundance of CCL2+ veins Decreased abundance of capillary clusters Decreased abundance of arterial clusters		Vascular barrier integrity Potential impairment of skeletal muscle mass and function	[27, 39, 55, 56, 60]
Skin	Transcriptional noise	Signatures of: DNA repair Cross-talk (EC-fibroblast, NOTCH3-HES1 axis)	Decreased abundance of capillary clusters		Decreased repair potential, vascular stiffening	[93, 94]

Common transcriptomic changes shared between multiple tissues are indicated in bold

EC endothelial cell; ECM extracellular matrix; BBB blood–brain barrier; FRS female reproductive system; TF transcription factor; DEG differentially expressed gene; IPF idiopathic pulmonary fibrosis; COPD chronic obstructive pulmonary disorder; SASP senescence associated secretory phenotype