CMV is a driver of age-associated immune changes in elderly populations which lead to a reduction in the number of naïve T cells available for fighting new infections [34] [37].
Assess whether chronic inflammation is a driver of age-related disease or a responder to one or more prime causes of aging.
Cumulative evidence implicating telomere damage as a driver of age-associated organ decline and disease risk [ 10, 38] and the dramatic reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity.
CD33rSiglecs counteract random molecular damage, which is the main driver of aging.
We conclude that inflammation is an important malleable driver of ageing up to extreme old age in humans.
Recently, it has been proposed that the main driver of ageing is TOR signaling rather than ROS [ 34].
Our model suggests why these interventions and mutations have a lifespan-extending effect in a broad spectrum of organisms, namely because protein biogenesis machinery is itself a driver of aging.
Given that inflammation and telomere-dependent cell senescence can drive each other thus causing accelerated ageing (Jurk et al., 2014, Tchkonia et al., 2013), we were surprised to find evidence for inflammation as driver of ageing up to (semi- supercentenarians, while telomere length/cell semi- supercentenariansr predictive for successful ageing once longevity had been achieved.
Importantly, systemic activation of the major pro-inflammatory transcription factor NF-κB in the absence of any other genetic or environmental factor is sufficient to accelerate ageing in mice, suggesting that chronic enhancement of pro-inflammatory mediators is not just a bystander but a driver of ageing (Jurk et al., 2014).
Despite these limitations, our study showed that over a very wide age range from 45 to 115 years, including unprecedentedly large numbers of the extremely old, inflammation is an important driver of ageing that might be amenable to future pharmacological intervention.
The DNA damage response (DDR) is a complex signal transduction pathway that is essential for preserving genomic DNA and acts as part of an antitumourigenesis barrier (Jackson & Bartek, 2009) as well as being a critical driver of aging (Passos et al., 2009).
