A study of mitochondria in spinal ganglion neurons during life: Quantitative changes from youth to extremely advanced age

Abstract

In view of the central role that mitochondria are thought to play in the ageing process, we investigated changes in mitochondria of spinal ganglion neurons in rabbits aged 1, 3.6, 6.7, and 8.8 years (the latter extremely old). Mitochondrial size increased significantly with age, while mitochondrial structure did not change. The total volume of mitochondria within the perikaryon did not change significantly during life. This indicates that in these neurons mitochondrial degradation was completely compensated by the production of new mitochondria even in the extremely advanced age. We also found that the mean volume of neuronal perikaryon increased markedly with age, so that the mean percentage of perikaryal volume occupied by mitochondria decreased significantly with a difference of about 33% between the youngest and the oldest animals. This decrease is only in very small part due to lipofuscin accumulation, so that the ratio of the total volume of mitochondria to the volume of functionally active cytoplasm decreased with age. The mitochondria of the neurons studied seem therefore unable to adapt their total volume to the volume of functionally active cytoplasm, that increases with age. This result is consistent with the observation that the neurons of old animals have a reduced ability to respond to high energy demands.

Mitochondria in Perineuronal Satellite Cell Sheaths of Rabbit Spinal Ganglia: Quantitative Changes during Life

“…In a previous study, the mean mitochondrial size increased significantly with age [Martinelli et al, 2003], and our present results reveal that this increase continues into extremely advanced age. Mitochondrial size also rises with age in the nerve cell bodies of rabbit spinal ganglia [Martinelli et al, 2006]. A comparison of the present findings with data on nerve cell bodies in the same ganglia shows that in each age group, the mean size of these organelles is the same in SCSs and neurons.…”

“…The reduced neuronal metabolism [Meier-Ruge et al, 1976;Mann et al, 1978;van den Bosch de Aguilar and Vanneste, 1980;Finch and Morgan, 1990] and the reduced ability of the neuron to respond to high energy demands [Sylvia and Rosenthal, 1979] in old age might be due in part to a diminished contribution from the perineuronal satellite cells. However, the mitochondrial changes found in neurons [Martinelli et al, 2006] and in perineuronal satellite cells (present study) of spinal ganglia were not associated with significant neuronal loss, as shown by the lack of degenerated or degenerating neurons even in extremely old animals. In other animal species, the number of spinal ganglion neurons does not decrease (humans [Emery and Singhal, 1973;Ohta et al, 1974] and rats [La Forte et al, 1991]) or only slightly declines (rats [Bergman and Ulfhake, 1998]) in senescence.…”

“…This decrease with age is rather due to the imbalance between mitochondrial degradation and the production of new mitochondria in favor of the former. A comparison of the present data on the mean percentage of cytoplasmic volume occupied by mitochondria in perineuronal sheaths with those from the nerve cell bodies of the same ganglia [Martinelli et al, 2006] showed that in all four age groups this percentage was greater in nerve cell bodies than perineuronal sheaths. The ratio between these two percentages (1.3: 1) did not change throughout life.…”

“…In view of the central role attributed to mitochondria in the aging process [for reviews, see Miquel et al, 1980;Wallace, 1992;Kadenbach et al, 1995;Ozawa, 1995;Cortopassi and Wong, 1999;Walter et al, 1999], we have quantitatively investigated age-related changes in mitochondria of spinal ganglion neurons in the rabbit [Ledda et al, 2001;Martinelli et al, 2006]. In spinal ganglia, each nerve cell body is usually enveloped by its own satellite cell sheath (SCS), thus constituting a structural and probably also a metabolic unit [for reviews, see Pannese, 1981Pannese, , 1994.…”

Morphological changes in nerve cells during normal aging

“…For this reason, markedly different quantities of lipofuscin are found in different regions of the nervous system of a given individual at any time. In any event, lipofuscin accumulation seems to have little or no effect on either the metabolism or functional activities of neurons.The structure of mitochondria does not appear to change with age, whereas a significant increase in mean mitochondrial size has been described in some regions of the nervous system (e.g., Martinelli et al 2006). With regard to changes in the percentage of perikaryal volume occupied by mitochondria with advancing age, conflicting data are present in the literature.…”