Measuring Impaired Autophagy With Aging in the Pancreas

Autophagy is the important collection of processes that break down damaged cellular components and unwanted metabolic byproducts. More autophagy improves the health of the organism and extends longevity, while less autophagy leads to the reverse. Boosted autophagy appears to contribute strongly to a number of life-extending interventions, including calorie restriction, and researchers have achieved such goals as reverting aged liver function to youthful levels by increasing the effectiveness of autophagic processes. Unfortunately, autophagy declines with age as the cellular components that carry out the process become damaged and overwhelmed by metabolic waste products. Here researchers measure the impact of reduced autophagy with age in the pancreas: "Type 2 diabetes is characterized by a deficit in β-cell function and mass, and its incidence increases with age. ... Impaired or deficient autophagy is believed to cause or contribute to aging and age-related disease. Autophagy may be necessary to maintain structure, mass, and function of pancreatic β-cells. In this study, we investigated the effects of age on β-cell function and autophagy in pancreatic islets of 4-month-old (young), 14-month-old (adult), and 24-month-old (old) male Wistar rats. We found that islet β-cell function decreased gradually with age. Protein expression of [autophagy markers] exhibited a marked decline in aged islets. The expression of Lamp-2, a good indicator of autophagic degradation rate, was significantly reduced in the islets of old rats, suggesting that autophagic degradation is decreased in the islets of aged rats. [Markers] of mitochondrial and nuclear DNA oxidative damage exhibited strong immunostaining in old islets. Analysis by electron microscopy demonstrated swelling and disintegration of cristae in the mitochondria of aged islets. These results suggest that β-cell and autophagic function in islets decline simultaneously with increasing age in Wistar rats, and that impaired autophagy in the islets of older rats may cause accumulation of misfolded and aggregated proteins and reduce the removal of abnormal mitochondria in β-cells, leading to reduced β-cell function. Dysfunctional autophagy in islets during the aging process may be an important mechanism leading to the development of type 2 diabetes." Reversing the decline in autophagy by restoring lysosomal function is a part of the SENS vision for rejuvenation biotechnology.



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