Graphical Abstract.

Schematic diagram summarizes dysfunctional key mechanisms and phenotypical features of cardiac ageing that are rescued by LAV-BPIFB4. Cardiac ageing is characterized by abnormal ribosomal biogenesis, DNA damage and senescence, and imbalance of inflammation and angiogenesis (red symbols and arrows). Left panel: Dysfunctional mechanisms rescued by LAV-BPIFB4 (green arrows). (i) Ribosomal biogenesis: LAV-BPIFB4 promotes rRNA transcription and ribosomal biogenesis. (ii) Senescence: LAV-BPIFB4 reduces the frequency of the Ki67^neg and gH2AX^pos antigenic phenotype and senescence markers SAβG, p16lnk4A and H3. (iii) Angiogenesis: LAV-BPIFB4 synergically works with NCL to induce vascular cell network formation. Right panel: LAV-BPIFB4 in carriers and effects of LAV-BPIFB4 supplementation to senescent vascular cells and aged mice. The LAV-BPIFB4 genotype is associated with partially preserved pericyte coverage. LAV-BPIFB4 supplementation rescues human pericytes in vitro and improves myocardial vascular density and cardiac function in aged mice.