Ageing as developmental decay: insights from p16INK4a

Lung tissue gene-expression signature for the ageing lung in COPD

“…The most abundant biological processes among the genes downregulated with age comprise development of the respiratory system and cell-cell contacts. The observations on developmental pathways are in line with the theory that ageing might be a result of developmental decay, stating that ageing occurs as a consequence of alterations in developmental pathways 16. For pathways related to cell-cell contacts, it has been shown that the permeability of the intestinal epithelium decreases with age in humans17 and decreased expression of tight junction molecules has been observed in aged rats 18.…”

Forging a signature of in vivo senescence

“…The closest thing to a testable prediction that requires measurement of in vivo senescence is in the area of mammalian ageing research. Subscribers to the senescence theory of ageing contend that at least some features of organismal ageing may stem from a progressive accumulation of senescent cells in tissues over a lifetime [156][157][158][159][160] , with the expectation that their enumeration in vivo might predict physiological age and longevity. Likewise, this model holds that 'senolytic' agents that are selectively toxic to senescent cells could trigger their clearance and reverse some aspects of ageing 161 .…”

“…Many aspects of mammalian ageing reflect a functional decline in the ability to maintain tissue homeo stasis and integrity, coupled with diminished responses to physiological demands under conditions of stress [156][157][158][159][160] . Ageassociated declines of functional reserves include the loss of replicative capacity in cells with self-renewal potential (particularly stem and progenitor cells) as well as increased age-dependent secretion of pro-inflammatory cytokines that could exacerbate potentially deleterious inflammatory responses and contribute to tissue injury.…”

Cellular aging dynamics after acute malaria infection: A 12‐month longitudinal study

“…In addition, shorter telomere length and reduced expression of telomerase regulatory genes have been reported in experimental malaria studies in birds (Asghar et al., 2016; Videvall, Cornwallis, Palinauskas, Valkiunas, & Hellgren, 2015). Besides being a valuable cellular senescence marker, CDKN2A has also been suggested to regulate telomerase activity in stem cells, where overexpression of CDKN2A suppresses hTERT (which encodes the catalytic unit of telomerase) (Martin, Beach, & Gil, 2014). Our results also suggest a negative correlation between CDKN2A and telomerase (hTERT) expression.…”