Accelerated structural decrements in the aging female rhesus macaque lung compared with males

Abstract

-Aging is associated with morphometric changes in the lung that lead to decreased lung function. The nonhuman primate lung has been shown to have similar architectural, morphological, and developmental patterns to that of humans. We hypothesized that the lungs of rhesus monkeys age in a pattern similar to human lungs. Thirty-four rhesus monkeys from the California National Primate Research Center were euthanized, necropsied, and the whole lungs sampled. Stereological analysis was performed to assess the morphological changes associated with age. The number of alveoli declined significantly from age 9 to 33 yr with a greater decline in females compared with males. Lungs of females contained roughly 20% more alveoli at age 9 yr than males, but by ϳ30 yr of age, females had 30% fewer alveoli than males. The volume of alveolar air also showed a significant linear decrease in females relative to age, while males did not. The numberweighted mean volume of alveoli showed a significant positive correlation with age in females but not in males. The volume of alveolar duct showed a significant positive correlation with age in females, but not in males. Structural decrements due to aging in the lung were increased in the female compared with male rhesus monkey. stereology; alveolar loss; alveolar duct enlargement OVER THE LAST SEVERAL decades, the median age of the US population has increased by 20 yr. The number of people age 65 yr and over is projected to increase from 35 million in 2000 to an estimated 71 million in 2030, with the largest increase in individuals age 80 yr and above (US Census 2005; http://www. census.gov/#). Numerous diseases are more frequently diagnosed in the aging lung including chronic obstructive pulmonary disease, pulmonary fibrosis, pneumonia, and lung cancer. Emphysema occurs more frequently in aged individuals and implies greater susceptibility of the aged lung to this disease (2). With the costs associated with maintaining an aging population that is increasing, it has become important to understand the process of aging in the lung and the diseases that can be associated with the aging process. An appropriate research model needs to be identified and characterized, both structurally and functionally, to understand the role of the aging process and how diseases exploit that process.Landmark work by Fletcher and Peto (4) demonstrated that the forced expiratory flow in 1 s (FEV 1 ) declines with age and that this decline is accelerated in active smokers with associated lung disease. In addition to accelerated decline of FEV 1 , there is an age-related loss of elastic recoil and decreased dynamic compliance with an increase in air flow resistance (1). The aging lung in humans is associated with numerous changes both functionally and structurally. The structural changes include an increase in alveolar duct volume, mean linear intercept, and the number of interalveolar pores (7, 23). However, a lack of representation of the oldest humans in physiological studies limits our understanding of pulmonar...

Growth of alveoli during postnatal development in humans based on stereological estimation

“…Previous estimates of the number of alveoli in the lungs of rhesus macaques were done using the same methodology (14,19,20). The values are reported in Fig.…”

“…(Table 1). Rhesus data were based on previous reports (14,19) and rat alveoli numbers (3, 24, 25). (Table 1).…”

A review of recent developments and applications of morphometry/stereology in lung research

“…Three papers on the postnatal development and aging of the rat, the nonhuman primate, and the human lung will be addressed (48,49,147). All of the three papers used state-of-the-art stereology and present a portfolio of detailed methods to assess lung alveolarization or age-associated loss of alveoli.…”

“…Their data clearly show that the major process of alveolarization takes place exponentially through the first 2 yr of postnatal life but continues at a much slower rate during adolescence. The loss of alveoli during aging was studied by the same group in the rhesus macaque and differentiated between male and female monkeys (48). Their data demonstrate a more pronounced loss of alveoli in the female monkeys compared with the males.…”

Lung Structure and the Intrinsic Challenges of Gas Exchange

“…However, later data using appropriate stereological techniques showed that alveoli increase in number, but not size during postnatal development in rhesus monkeys (187). As rhesus monkeys age, there is a significant loss of alveoli that is 30% greater in postmenopausal females than males (134). The great apes that assume an upright position exhibit anatomical relationships among lungs, thorax, heart, and diaphragm that closely resemble those in humans.…”