Deficit accumulation as an explanation for ageing and frailty – from the subcellular to the substantial

Prof Kenneth Rockwood is Director of Geriatric Medicine Research at Dalhousie University, Canada and serves on the International Advisory Panel of Age and Ageing journal.

Prof Susan Howlett is  also at Dalhousie, University, Canada in the Department of Pharmacology.

A lot happens at the molecular and cellular levels as we age. A recent review in Cell  identified nine hallmarks of ageing, including genomic instability, mitochondrial dysfunction, cellular senescence and stem cell exhaustion.  These, of course, are intrinsically inter-related; the DNA damage that underlies the hallmark genomic instability accelerates with telomere shortening (another hallmark) and is associated with altered protein homeostasis (another hallmark still). This molecular and cellular deficit accumulation is now widely understood as the basis of how we age.