Role of Mitochondrial Deterioration in Physiological and Pathological Brain Aging

Abstract

Background: Mitochondria are widely reported to occupy a unique role in modulating cell viability, senescence and death. This is consistently supported by the multiple functions of these organelles. In addition to providing the energy for the myriad of cellular performances, mitochondria are involved in regulating thermogenesis, calcium buffering, integration of pro- and anti-apoptotic signals. Objective: To stress the significant importance of subtle, continuous and permanent mitochondrial alterations as key events in physiological aging and as unfavourable determinants of age-related neurodegenerative diseases. Results: Any dysfunction of these organelles may constitute a serious threat for cellular health status and survival, particularly of post-mitotic nerve and muscle cells. Mitochondrial deterioration may affect discrete features of the organelles (such as their structural dynamics, genetics and physiology) and lead to a progressive functional impairment. Conclusions: A variety of mitochondrial tasks, while hampering the possibility to recover the organelles’ dysfunctions, offer different and reliable opportunities for therapeutic interventions.

Age-related decline in metabolic competence of small and medium-sized synaptic mitochondria

“…2a). These findings lend support to the critical role played by the mitochondria in the process of aging (Bertoni-Freddari et al 2004) and provide novel information on the extent of age-related mitochondrial dysfunction with reference to the organelle's size. In agreement with recent confocal microscopy studies (Collins et al 2002), our results document that mitochondria show a wide range of morphological features and are functionally heterogeneous.…”

“…the fraction of mitochondria/mm 3 of tissue or cytoplasm) remains constant with advancing age (Bertoni-Freddari et al 1993). This significant remodelling of mitochondrial morphology (specifically, the paired increase in size and decrease in number) has been reported to be a general trend in aging and is interpreted as a functionally dynamic adaptive response of the mitochondria to the changing energy demands from the environmental framework (Walter et al 1999;Bertoni-Freddari et al 1993, 2004. Our previous study (Bertoni-Freddari et al 2003) and the present findings document that oversized organelles show very low R values, however, since their fraction (percent) increases in aging, an effective compensation due to the complement of enlarged mitochondria can be supposed to occur in old cells.…”

“…b Age comparison of the quartile values of MA. The old animals consistently showed higher values of MA for the age-paired comparisons between quartiles I, II and III (+10.3, +6.6, +5.7%, respectively), however, only oversized mitochondria (quartile IV) were significantly larger (+18.6%) in the old versus the adult animals alterations are reported to represent very early changes in the process of aging and they have been documented to occur in single neurones or discrete groups of nerve cells (Bertoni-Freddari et al 2001, 2004.…”

Análise da expressão das proteínas Rab anterior à agregação proteica associada a neurodegeneração

“…Muito embora um evento causativo para a deficiência da sinapse no envelhecimento não possa ser definitivamente caracterizado devido aos múltiplos determinantes da fisiologia do envelhecimento encefálico, alguns experimentos demonstraram a importância da presença de mitocôndrias no terminal sináptico para a modulação/dinâmica da sinapse e neuroplasticidade sináptica (Bertoni-Freddari et al, 1993, Bertoni-Freddari et al, 2004, BertoniFreddari et al, 2007b.…”

Avaliação de pacientes com esclerose mesial temporal pela espectroscopia de fósforo por ressonância magnética em aparelho 3T

“…As mudanças no metabolismo energético podem estar relacionadas a alterações funcionais e morfológicas que a mitocôndria sofre com o envelhecimento, incluindo redução no número, alteração da forma, tamanho, composição estrutural, redução do consumo de oxigênio e da síntese de ATP (Bertoni-Freddari et al, 2004).…”