Anti-aging effects of anti-lipolytic drugs
Abstract
Genetic disruption of insulin and insulin-like signaling pathways may extend lifespan. Hyperinsulinemia and insulin resistance may accelerate aging. The hypothesis was tested that a once-a-week life-long inhibition of insulin secretion by the administration of anti-lipolytic drugs might have anti-aging effects. Groups of 3-month-old male Sprague-Dawley rats were (a) given standard laboratory food ad libitum (AL); (b) fed AL 6 days and fasted 1 day every week (FW); (c) fed AL every other day (EOD), (d) fed like FW and given Acipimox (50 mg/kg b.w.) on the day of fasting (FWA) by the gastric tube. The AL, FW and EOD groups received saline intragastrically. Treatment with ACIPIMOX transiently decreased plasma free fatty acids, glucose and insulin and increased valine plasma levels, and had no long-term effect on food consumption and body weight. By age 6, 12 and 24 months subgroups were taken and the age-related changes in liver dolichol and autophagic proteolysis--which are correlated with life-expectancy--were measured. Liver dolichol levels increased and autophagic proteolysis decreased in mature and older AL rats; EOD and FWA fully counteracted these changes; FW rats had significant but smaller beneficial effects. It is concluded that life-long weekly-repeated transient inhibition of insulin secretion by antilipolytic drugs may have an anti-aging effect, additive to the anti-aging effect of a milder caloric restriction. Speculation is that transiently lower plasma insulin le…
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Caloric restriction and treatment with lipogenic agents are able to prevent the dysregulation of macroautophagy in old rodents, although the mechanisms are still under investigation.
“Caloric restriction and treatment with lipogenic agents are able to prevent the dysregulation of macroautophagy in old rodents, although the mechanisms by which they exert their action is still subject of investigation (Cavallini et al., 2001; Donati et al., 2004).”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Donati et al., 2004
Cites
Age-dependent accumulation of dolichol in rat liver: is tissue dolichol a biomarker of aging?
Marino, M., Dolfi, C., Paradiso, C., Cavallini, G., Masini, M., Gori, Z., Pollera, M., Trentalance, A., & Bergamini, E. (1998) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/53a.2.b87 · Cited by 47 · see citing works
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Autophagy and aging: The importance of maintaining "clean" cells
Cuervo, A. M., Bergamini, E., Brunk, U. T., Dröge, W., Ffrench, M., & Terman, A. (2005) · Autophagy · doi:10.4161/auto.1.3.2017 · Cited by 792 · see citing works
Self-citationProtein Homeostasis and Aging: the importance of exquisite quality control
Koga, H., Kaushik, S., & Cuervo, A. M. (2011) · Ageing research reviews · doi:10.1016/j.arr.2010.02.001 · Cited by 476 · see citing works
Corton, J. C., & Brown-Borg, H. M. (2005) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/60.12.1494 · Cited by 106 · see citing works
- Authors
- Donati, A., Cavallini, G., Carresi, C., Gori, Z., Parentini, I., & Bergamini, E.
- Affiliations
- University of Pisa (IT)
- Corresponding author
- Bergamini, Ettore
- ORCID
- Cavallini, Gabriella
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 39
- Issue
- 7
- Pages
- 1061-1067
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2132940351
- Cited by
- 37
- References
- 1
- Citations by year
- 2022: 1 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- anti-aging, acipimox, insulin secretion inhibition, insulin resistance, hyperinsulinemia, caloric restriction, intermittent fasting, autophagy, plasma free fatty acids, aging
- MeSH terms
- Aging, Animals, Hypolipidemic Agents, Autophagy, Blood Glucose, Energy Intake, Chromatography, High Pressure Liquid, Dolichols, Fatty Acids, Nonesterified, Insulin, Liver, Male, Pyrazines, Rats, Sprague-Dawley, Caloric Restriction, Rats
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