Biology subjects

Ahmet, I.

Publications and source records attributed to Ahmet, I..

3 recordsLinked to original sources

bioRxiv2023

The Therapeutic Effects of Long-term Photobiomodulation on Aging in Mice

BackgroundWe have reported that photobiomodulation (PBM) therapy, a form of low dose Near Infrared Light (NIR) therapy, attenuates cardiovascular remodeling and extends the lifespan in a mouse model of accelerated cardiac aging. Here, we tested whether long-term PBM affects the aging process in normal male and female mice. MethodsC57 mice, 18 months old, males (n=60) and females (n=60), were exposed to either NIR (850nm) at 25 mW/cm2 for 2 min on weekdays (MT and FT groups) or nothing (M and F groups) for 12 months. Mice were subjected to bimonthly echocardiography examination, Gait analysis and Frailty assessments. Randomly selected mice were sacrificed bimonthly for fresh tissue samples. ResultsAge-associated deterioration in left ventricle, left atrium, aorta, brain blood perfusion, frailty, body temperature and gait that were observed in M and F groups during the 12-month observation period were significantly attenuated by PBM therapy in MT and FT groups. The medium lifespan was extended by 0.6 and 1.0 month in MT and FT groups, compared to M and F groups, respectively. There was a significantly lower prevalence of dermatitis, stroke and heart failure in MT and FT groups compared to M and F groups. ConclusionOur data showed for the first time that PBM therapy by whole body exposure, even started at old age in normal animals, significantly attenuated the age-associated deterioration in heart, vessels, brain, gait and frailty; reduced the prevalence of stroke and heart failure; and improved health span.

physiology↗

bioRxiv2022

A Remarkable Adaptive Paradigm Of Heart Performance And Protection Emerges In Response To The Constitutive Challenge Of Marked Cardiac-Specific Overexpression Of Adenylyl Cyclase Type 8

Adult mice with cardiac-specific overexpression of adenylyl cyclase (AC) type VIII (TGAC8) adapt to an incessantly increased cAMP-induced cardiac workload ([~]30% increases in heart rate, ejection fraction and cardiac output) for up to a year without signs of heart failure or excessive mortality. Here we show that despite markedly increased cardiac work, classical cardiac hypertrophy markers were absent in TGAC8, total left ventricular (LV) mass was not increased: a reduced LV cavity volume in TGAC8 was encased by thicker LV walls harboring an increased number of small cardiac myocytes and a network of small interstitial non-cardiac myocytes, manifesting increased proliferation markers and compared to WT. Protein synthesis, proteosome activity, autophagy, and Nrf-2, Hsp90, ACC2 protein levels were increased in TGAC8, but LV ATP and phosphocreatine levels in vivo did not differ by genotype. 2,323 transcripts and 2,184 proteins identified in unbiased omics analyses, spanning a wide array of biological processes and molecular functions in numerous cellular compartments differed in TGAC8 vs WT; and over 250 canonical signaling pathways characteristic of adaptive survival circuitry of cancers, including PI3K and growth factor signaling, cytokine and T cell receptor signaling, immune responses, ROS scavenging, proliferation, protection from apoptosis, and nutrient sensing, were activated in TGAC8; and compared to WT there was a shift from fatty acid oxidation to increased aerobic glycolysis in the context of increased utilization of the pentose phosphate shunt and nucleotide synthesis. Thus, the adaptive paradigm, that becomes activated in the LV of TGAC8 in response to severe chronic, intense AC/PKA/Ca2+ signaling embodies many hallmarks of cancer.

physiology↗

bioRxiv2022

Emergence of Heartbeat Frailty in Advanced Age: Perspectives from Life-Long EKG Recordings in Mice

SAN failure, aka sick-sinus syndrome, which features sinus bradycardia, SAN impulse pauses, and irregularity of RR interval rhythms are manifestations of SAN cell dysfunction that increases exponentially with advanced age, i.e., SAN frailty. Abnormalities in intrinsic RR interval variability may be the earliest signatures of SAN cell dysfunction leading to SAN frailty in late life. We measured RR interval variability within EKG timeseries prior to and during double autonomic blockade in long-lived C57/BL6 mice at 3 month intervals from 6 months of age until the end of life. Long-lived mice (those that achieved the median cohort lifespan of 24 months and beyond) displayed relatively minor changes in intrinsic RR interval variability prior to 21 months of age. Between 21 and 30 months of age, marked changes in intrinsic RR interval variability signatures in time, frequency, non-linear, and fragmentation domains result in a marked increase in the mean intrinsic RR interval. The effects of autonomic input partially compensated for the prolongation of the mean RR interval by impacting the age-associated deterioration in the RR interval variability signatures toward a youthful pattern. Cross-sectional analyses of other subsets of mice at ages at or beyond the median life span of our longitudinal cohort demonstrated increased non-cardiac, constitutional, whole body frailty, a decrease in energetic efficiency, and an increase in respiratory exchange ratio. In this context, we interpret the progressive increase in intrinsic RR interval variability beyond 21 months of age to be an indication of heartbeat frailty.

physiology↗