There are studies suggesting that senescence in microglia causes them to function abnormally and that the destructive roles of activated microglia in the aged neurodegenerative brain may result from age-associated microglia senescence, causing a failure of the aged microglia to respond correctly to stimuli [147, 148] and eventually promoting neurodegeneration [149] (Figure 1 ). The most prominent and also the initially identified feature of microglial senescence is the morphological alteration described as "dystrophy" [150] . Characteristics of "dystrophic" microglia observed in the aged brain include de-ramification (the loss of finely branched cytoplasmic processes), cytoplasmic beading/ spheroid formation, shortened and twisted cytoplasmic processes, and instances of partial or complete cytoplasmic fragmentation [150] . Such dystrophic microglia were prevalent and extensively distributed in the brain of older human subjects [150, 151] , whereas normally ramified microglial morphology with only rare instances of dystrophic microglia is observed in the young brain [148] . These observations provide initial evidence for the age-associated changes in microglia in the healthy elderly brain. Telomere shortening, a marker of aging, has also been demonstrated in microglia in the aged brain in Flanary's study, who reported that microglial cells in rats exhibit significant telomere shortening and a reduction in telomerase activity during normal aging [152] . More importantly, microglial senescence is also manifested by functional alterations, such as an altered inflammatory profile, increased immunophenotypic expression, and the switch from neuroprotective Luo and Chen Translational Neurodegeneration 2012, 1:9 Page 5 of 13 http://www.translationalneurodegeneration.com/content/1/1/9 in the young brain to neurotoxic in the aged brain upon activation [147] . Also, the timing of microglial proliferation and presentation in the injured aged brain is distinct from that in the young brain. For example, Conde et al. reported that microglial proliferation rates in the aged rat brain were significantly higher than in the young rat brain four days after axotomy of the facial nerve [148] . The distinct pattern of the microglial response to injury in the aged brain has also been recorded in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model of neurotoxicity [153] , the model of controlled cortical impact (CCI) [154] , cortical stab injury [155] and transient retinal ischemia [156] . Although more attention has been paid to the dysfunction of aged microglia, many critical questions remain unanswered. Some of these questions are: whether the activated state of microglia in the aging brain is concurrent with or secondary to microglial dystrophy; which specific function of microglia is primarily affected by microglial dystrophy, how it is affected and what is the direct consequence of the affected function; and whether the deterioration of a specific microglial function is more related to neurodegeneration than others. Clearly, more research is needed to answer these questions.