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New Anti-Aging Drugs Senolytics & Mitochondria/Aging HIV, Brain/diabetes, Muscles
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Senolytics improve physical function and increase lifespan in old age
Our study provides proof-of-concept evidence that senescent cells can cause physical dysfunction and decreased survival even in young mice, while senolytics can enhance remaining health- and lifespan in old mice.
https://www.natap.org/2020/HIV/061720_02.htm
https://www.natap.org/2020/HIV/nrd.2018.44(2).pdf
Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease
The first human trial of senolytics in patients with idiopathic pulmonary fibrosis (NCT02874989) investigated dasatinib (a tyrosine kinase inhibitor or TKI) in combination with quercetin (a plant flavanol that targets BCL-2, insulin/IGF-1, and HIF1-alpha), demonstrating the safety and tolerability of these compounds in association with improved physical function [142].
In animal models of aging, the efficacy of metformin led to the Targeting Aging with Metformin (TAME) Trial (managed by the American Foundation for Aging Research), investigating this drug as a novel senotherapeutic in HIV-uninfected persons. https://www.natap.org/2020/HIV/072720_01.htm
Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms
Increased Risk of Cognitive Impairment in Patients With Diabetes Is Associated With Metformin
Metformin Use Is Associated With Slowed Cognitive Decline and Reduced Incident Dementia in Older Adults With Type 2 Diabetes: The Sydney Memory and Ageing Study
Use of Senolytics: Anti-Aging Drugs; in PLWH Study
Skeletal muscle mitochondrial dysfunction in contemporary antiretroviral therapy: a single cell analysis
Overall, 40% of SUN study participants aged ≤50 years with well-controlled HIV infection were pre-frail or frail.
Impaired functional capacity is strongly associated with lower bone density and lower muscle mass in middle-aged HIV-1+ persons.
"Frailty is a significant predictor of mortality among both HIV+ and at-risk IDU....... Impaired functional capacity is strongly associated with lower bone density and lower muscle mass in middle-aged HIV-1+ persons......Co-morbidity Is Predictive of Muscle Strength in HIV+ Veterans: Results from the VACS Index....https://www.natap.org/2012/CROI/croi_31.htm
Mitochondrial DNA damage in brain associated with HIV infection
The combined effects of increased tubular TFV exposure, of RTV or COBI on tubular TFV excretion and/or of RTV or COBI on eGFR by inhibiting the tubular creatinine transporter multidrug and toxin extrusion 1 (MATE1) without affecting the actual GFR [58] may contribute to these greater eGFR reductions.
Tenofovir-DF and ATV are best avoided in patients with CKD
RELATIONSHIP OF T-CELL MITOCHONDRIAL GENE EXPRESSION AND DIABETES IN PERSONS WITH HIV - (03/28/21)
PLWH who have T2DM have reduced single cell mtDNA gene expression compared to those without T2DM in both circulating and subcutaneous adipose tissue CD4+ and CD8+ T cells.
TENOFOVIR ALAFENAMIDE IS ASSOCIATED WITH SHORTER TELOMERE LENGTH IN PEOPLE WITH HIV - (10/18/22)
AGE: Muscle mitochondrial function and contemporary anti-retroviral therapy - (09/19/18)
LOWER MITOCHONDRIAL DNA COPY NUMBER IS ASSOCIATED WITH HIV & PREDICTIVE OF MORTALITY
Gait Speed/Mitochondria/ Functional Decline in HIV+ - The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living with HIV
mitochondrial function among PLWHIV could be damaged by HIV chronic infection [14] and long-term usage of ART [13], which trigger proinflammatory responses that could lead to impaired physical function.....having ever been diagnosed with AIDS, higher viremia copy-year, were associated with more rapid decline of gait speed(Supplemental Table 1)
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