Thursday, June 10, 2004

Gene expression in aging human brains

There's an interesting study in Nature and reported in today's Wall Street Journal that used Affymetrix arrays to do expression profiling on brain tissue across a wide age range.

As Early as Age 40, Genes in the Brain Begin to Deteriorate (WSJ) (They mention Affy in the last paragraph.)

Gene regulation and DNA damage in the ageing human brain" by Lu et al. (Nature)

The ageing of the human brain is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease. The time in life when brain ageing begins is undefined. Here we show that transcriptional profiling of the human frontal cortex from individuals ranging from 26 to 106 years of age defines a set of genes with reduced expression after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. This is followed by induction of stress response, antioxidant and DNA repair genes. DNA damage is markedly increased in the promoters of genes with reduced expression in the aged cortex. Moreover, these gene promoters are selectively damaged by oxidative stress in cultured human neurons, and show reduced base-excision DNA repair. Thus, DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a programme of brain ageing that starts early in adult life.

This study used the HG-U95Av2 arrays. The WSJ reports that the authors are repeating the study using newer (U133) arrays.

I imagine this report will get increased attention in light of the fanfare surrounding
Ronald Reagan's death.

Keep taking those antioxidant supplements & drinking green tea folks! :-)

1 comment:

  1. From an evolutionary point of view, one might surmise that since cognitive brain function is not required for reproduction, there is no selective pressure against these mutations.

    Cognitive function isn't required for reproduction per se, but given the social complexity of our species, it is required for finding mates and for raising offspring. So the age this study found where expression changes and mutations start piling up (42) I think reflects a species-wide average of the time it takes to have kids and to get them out on their own (say 24 years + 18 years). Coincidentally, age 42 is also the average age when most women's fertility undergoes a precipitous drop (see this link). Perhaps the reason behind this drop is related to the brain function drop?

    People having kids late in life (such as myself) are operating in a kind of evolutionary no-man's land. I like to think that we're putting pressure on our species to delay the onset of cognitive decline a few more years!