Regardless of the precise underlying molecular mechanisms, the fundamental defining manifestation of ageing is an overall decline in the functional capacity of various organs to maintain baseline tissue homeostasis and to respond adequately to physiological needs under stress3,5. In many aged tissues, these declines are gradual and modest in middle years but accelerate rapidly late in life and become particularly apparent under conditions that challenge the organism to overcome various stressors with a robust physiological or regenerative response. At the anatomical and physiological levels, diminished tissue cellularity and inadequate regenerative responses seem to be intimately linked to many of the classic age-associated medical maladies, such as muscle atrophy, anaemia, feeble immune responses and impaired wound healing (Box 1).
