2002

Hear Res. 2002 Jul;169(1-2):24-35.
Effects of caloric restriction and aging on the auditory function of rhesus monkeys (Macaca mulatta): The University of Wisconsin Study.
Fowler CG, Torre P 3rd, Kemnitz JW.
Department of Communicative Disorders, University of Wisconsin-Madison, Wisconsin Regional Primate Center, 1975 Willow Drive, Madison, WI 53706, USA.

The present study is part of a larger project that investigates the effect of caloric restriction on longevity in the rhesus monkey. The purpose of the present study was to document presbycusis and the effect of caloric restriction on presbycusis in monkeys. The control group had 35 monkeys allowed to eat freely and the caloric-restricted group (CR) had 33 monkeys with a 30% reduction in caloric intake. Monaural and binaural auditory brainstem response (ABR) and middle latency response (MLR) were obtained from 27 female and 41 male monkeys that were 11-23 years of age and had been in the study for 102, 42, or 36 months when tested. Significant findings were the following: (1) wave I amplitudes were larger for females and for younger monkeys, and amplitudes decreased in aging males but not in aging females; (2) wave IV amplitudes were larger for females than males, and amplitudes for CR females were larger than for female controls, whereas the amplitudes from control and CR males were not different; (3) wave Pa latencies were shorter for females, and shorter latencies were maintained for aging females but not for aging males; (4) interwave interval IV-Pa was shorter for females, and intervals lengthened for aging males but not aging females; (5) binaural wave IV amplitude decreased faster with age for control monkeys than for CR monkeys, and the L+R Pa amplitude decreased with age. Additional trends were identified for longitudinal monitoring as monkeys enter old age.

2000

Laryngoscope 2000 May;110(5 Pt 1):727-38.
Effects of dietary restriction and antioxidants on presbyacusis.
Seidman MD.
Department of Otolaryngology-Head and Neck Surgery, Henry Ford Health System, West Bloomfield, Michigan 48323, USA.

OBJECTIVES/HYPOTHESIS: The premise of this study is that the membrane hypothesis of aging, also known as the mitochondrial clock theory of aging, is the basis for presbyacusis. Furthermore, it is proposed that treatment with antioxidants or dietary restriction can attenuate age-related hearing loss. Many studies have demonstrated a reduction in blood flow to specific tissues, including the cochlea, with aging. Hypoperfusion leads to the formation of reactive oxygen metabolites (ROM). ROM are highly toxic molecules that directly affect tissues including inner ear structures. In addition, ROM can damage mitochondrial DNA (mtDNA), resulting in the production of specific mtDNA deletions (mtDNA del4977 [human] or mtDNA del4834 [rat]; also known as the common aging deletion]. Previous corroborating data suggest that the common aging deletion mtDNA4834 may be associated not only with aging but also with presbyacusis, thus further strengthening the basis of the current studies. In this study, experiments provide compelling evidence that long-term treatment with compounds that block or scavenge reactive oxygen metabolites attenuate age-related hearing loss and reduce the impact of associated deleterious changes at the molecular level. STUDY DESIGN: Prospective randomized study. METHODS: One hundred thirty rats were randomly assigned to one of six groups with appropriate controls. Animals were divided into the following treatment arms: group 1, 30% caloric restriction; group 2, vitamin E oversupplementation; group 3, vitamin C over-supplementation; group 4, melatonin treatment; group 5, lazaroid treatment; and group 6, placebo. In addition, 10 animals were used to determine the appropriate caloric restriction. All subjects underwent baseline and every-3-month testing until their health failed (range, 18-28 mo; average, 25 mo). This testing included auditory sensitivity studies using auditory brainstem response (ABR) testing, as well as tissue analysis for mtDNA deletions using molecular biological techniques. At the conclusion of the study, animals underwent a final ABR test and were tested for mtDNA deletions in brain and inner ear tissues, and the opposite ear was used for histological analysis. RESULTS: Results indicated that the 30%-caloric-restricted group maintained the most acute auditory sensitivities, the lowest quantity of mtDNA deletions, and the least amount of outer hair cell loss. The antioxidant-treated subjects had improved auditory sensitivities, and a trend for fewer mtDNA deletions was observed compared with the placebo subjects. The placebo subjects had the poorest auditory sensitivity, the most mtDNA deletions, and the greatest degree of outer hair cell loss. CONCLUSIONS: Intervention designed to reduce reactive oxygen metabolite damage appears to protect against age-related hearing loss specifically and aging in general. This is reflected by an overall reduction in mtDNA deletions. These data also suggest that the common aging deletion appears to be associated with presbyacusis, as demonstrated by an increased frequency of the mtDNA del4834 in the cochleae with the most significant hearing loss. Nutritional and pharmacological strategies may very well provide rational treatment options that would limit the age-associated increase in ROM generation, reduce mtDNA damage, and reduce the degree of hearing loss as the organism advances in age.

1988

Audiology. 1988;27(6):305-12.
Dietary restriction and presbyacusis: periods of restriction and auditory threshold losses in the CBA/J mouse.
Sweet RJ, Price JM, Henry KR.
Department of Psychology, University of California, Davis.

Dietary restriction was imposed on CBA/J mice, animals which develop presbyacusis late in their lives. Animals restricted for their whole lives, as well as those restricted after midlife, had less presbyacusis than did control mice fed ad libitum. Dietary restriction did not increase the life spans of these mice. Restriction until midlife did not protect from presbyacusis, nor did it increase life span. In this genotype, dietary restriction protects against hearing loss only if it occurs at the age of most rapid decline of cochlear function.

1986

Audiology. 1986;25(6):329-37.
Effects of dietary restriction on presbyacusis in the mouse.
Henry KR.
Department of Psychology, University of California, Davis.

If dietary restriction can extend the human life span, it would be useful to know whether presbyacusis would continue its normal pace. This question was experimentally addressed, using the mouse as a model. Alternate-day feeding and fasting resulted in restricted mice of the AKR and AU/Ss inbred strains weighing less than their continuously fed controls. Restriction did not increase the life span or alter presbyacusis of the AKR mouse, but it improved both functions in the AU/Ss mouse. Their life spans were increased by 40%, and cochlear functions were better than controls at every age at which animals of both groups were still alive. Nonetheless, the oldest remaining restricted AU/Ss mouse had greater cochlear loss than was seen in any AU/Ss control mice. This study demonstrates that dietary restriction can slow the cochlear losses in a mammal which has a presbyacusis condition similar to that of humans.