Most older individuals develop inflammageing, a condition characterized by elevated
levels of blood inflammatory markers that carries high susceptibility to chronic morbidity,
disability, frailty, and premature death. Potential mechanisms of inflammageing include
genetic susceptibility, central obesity, increased gut permeability, changes to microbiota
composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress
caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections.
Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials
suggest that this association is causal. Inflammageing is also a risk factor for chronic
kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but
whether modulating inflammation beneficially affects the clinical course of non-CVD
health problems is controversial. This uncertainty is an important issue to address
because older patients with CVD are often affected by multimorbidity and frailty -
which affect clinical manifestations, prognosis, and response to treatment - and are
associated with inflammation by mechanisms similar to those in CVD. The hypothesis
that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors,
increasing catabolism, and interfering with homeostatic signalling is supported by
mechanistic studies but requires confirmation in humans. Whether early modulation
of inflammageing prevents or delays the onset of cardiovascular frailty should be
tested in clinical trials.