Short senolytic or senostatic interventions rescue progression of radiation-induced frailty and premature ageing in mice

Cancer survivors suffer from progressive frailty, multimorbidity and premature morbidity. We hypothesize that therapy-induced senescence and senescence progression via bystander effects is a significant cause of this premature ageing phenotype. Accordingly, the study addresses the question whether a short anti-senescence intervention is able to block progression of radiation-induced frailty and disability in a pre-clinical setting. Male mice were sub-lethally irradiated at 5 months of age and treated (or not) with either a senolytic drug (Navitoclax or dasatinib + quercetin) for 10 days or with the senostatic metformin for 10 weeks. Follow up was for one year. Treatments commencing within a month after irradiation effectively reduced frailty progression (p<0.05) and improved muscle (p<0.01) and liver (p<0.05) function as well as short-term memory (p<0.05) until advanced age with no need for repeated interventions. Senolytic interventions that started late, after radiation-induced premature frailty was manifest, still had beneficial effects on frailty (p<0.05) and short-term memory (p<0.05). Metformin was similarly effective as senolytics. At therapeutically achievable concentrations metformin acted as a senostatic neither via inhibition of mitochondrial complex I, nor via improvement of mitophagy or mitochondrial function, but by reducing non-mitochondrial ROS production via NOX4 inhibition in senescent cells. Our study suggests that the progression of adverse long-term health and quality-of-life effects of radiation exposure, as experienced by cancer survivors, might be rescued by short-term adjuvant antisenescence interventions.

Pulmonary Alveolar Stem Cell Senescence, Apoptosis, and Differentiation by p53-Dependent and -Independent Mechanisms in Telomerase-Deficient Mice

Pulmonary premature ageing and fibrogenesis as in idiopathic pulmonary fibrosis (IPF) occur with the DNA damage response in lungs deficient of telomerase. The molecular mechanism mediating pulmonary alveolar cell fates remains to be investigated. The present study shows that naturally occurring ageing is associated with the DNA damage response (DDR) and activation of the p53 signalling pathway. Telomerase deficiency induced by telomerase RNA component (TERC) knockout (KO) accelerates not only replicative senescence but also altered differentiation and apoptosis of the pulmonary alveolar stem cells (AEC2) in association with increased innate immune natural killer (NK) cells in TERC KO mice. TERC KO results in increased senescence-associated heterochromatin foci (SAHF) marker HP1γ, p21, p16, and apoptosis-associated cleaved caspase-3 in AEC2. However, additional deficiency of the tumour suppressor p53 in the Trp53−/− allele of the late generation of TERC KO mice attenuates the increased senescent and apoptotic markers significantly. Moreover, p53 deficiency has no significant effect on the increased gene expression of T1α (a marker of terminal differentiated AEC1) in AEC2 of the late generation of TERC KO mice. These findings demonstrate that, in natural ageing or premature ageing accelerated by telomere shortening, pulmonary senescence and IPF develop with alveolar stem cell p53-dependent premature replicative senescence, apoptosis, and p53-independent differentiation, resulting in pulmonary senescence-associated low-grade inflammation (SALI). Our studies indicate a natural ageing-associated molecular mechanism of telomerase deficiency-induced telomere DDR and SALI in pulmonary ageing and IPF.

Success and Development of Older Workers as a Challenge to Higher Education

The article implements an attempt to present the success of older workers in the conditions of the sporting paradigm and the formation of eco-thinking in organizations. The reasons for rethinking the prolonged working capacity of age workers as a “new normal” are shown. The article dwells on the features of teaching employment in higher education and makes the case for forming environmental conditions in universities to retain key professors and associate professors so that they can continue their creative work. The authors give characteristics of successful, healthy, active and productive ageing and suggest the measures that help to slow down the premature ageing of personnel.

23 Frailty, Older Age-Associated Conditions, and Multimorbidity Amongst People Experiencing Homelessness in A Hostel in London

Introduction People experiencing homelessness (PEH) face poor health outcomes and extreme health inequity, and evidence suggests earlier onset of older age-associated conditions and signs of premature ageing. This is the first UK study to assess frailty in this population. The objective was to assess frailty, age-associated conditions, and multimorbidity in PEH residing in hostel accommodation, drawing comparisons with population data. Methods Participants were drawn from a hostel in London for PEH aged over 30. Age-associated conditions were identified using validated tools and a questionnaire modelled on comprehensive geriatric assessments. Participants’ keyworkers completed questionnaires to provide collateral information. Frailty was defined according to five criteria in Fried’s phenotype model: participants with three or more criteria are classified as frail, one or two criteria as vulnerable, and no criteria as not frail. Multimorbidity was defined as the presence of two or more long-term conditions in one person. Comparisons were made with population data from The English Longitudinal Study of Ageing and Health Survey for England. Results Thirty-three people participated (83% of eligible residents), with a mean age of 55.7 years (range 38–74). Frailty was identified in 18/33 participants (55%), with 13/33 (39%) classified as vulnerable, and 2/33 (6%) as not frail. Participants met an average of 2.6/5 frailty phenotype criteria, comparable to 90-year-olds in the general population. The most common age-associated conditions identified were: falls (in 61%), visual impairment (61%), low grip strength (61%), mobility impairment (52%), and cognitive impairment (45%). Multimorbidity was present in all thirty-three participants. Conclusions A wide range of unmet health needs was identified. The high prevalence of frailty and age-associated conditions support evidence of premature ageing, indicating a need to include holistic older-age assessments in PEH at a younger age. Involvement of health professionals with experience of working with older people could contribute to improving health outcomes for homeless patients.

A case study on Antiaging property of Mandukparni as an Ayurvedic cosmetic drug

We use cosmetics for keeping and improving natural beauty. The most common problem today is premature ageing of skin. Ayurvedic cosmetics include healthy lifestyle and use of medicinal herbs. Mandukparni is one of those herbal drugs, which is frequently used in Antiaging creams. Hence, we had made attempt to explore antiaging effect of Mandukparni on skin. A female patient of 39 years old at OPD of SRC Ayurveda college, Chikhli was selected for study. She had given Mandukparni churna in the form of lepa and also internally for 30 days. After treatment Mandukparni showed improvement in Wrinkles, Blemishes, Hyperpigmentation, Blackheads, Oiliness. Hence it can be concluded that Mandukparni is an Ayurvedic cosmetic drug showing surprising effect on skin.

“Review on premature white and grey hair in children.”

Skin and hair colour contribute significantly to our overall visual appearance of person. The description of kesha and palitya is scattered in all the treatises of ayurveda. In ayurveda premature greying of hair is called as akalapalitya. The incidence of premature ageing along with akala palitya is on increase. These days the quality of hair products has degraded over the years. This review has been undertaken to the various causes of greying hair in children.

A CRITICAL APPRAISAL ON AGEING PROCESS IN AYURVEDA

Ayurveda being essentially the science of life and longevity narrates all aspects of life and puts special emphasis on Jara (ageing). The world population of the elderly is increasing and by the year 2030, older persons are projected to account for one in six people globally. Ageing is a process of unfavorable progressive changes associated with decline in vigor and ending in death. It is an irreversible and inevitable process and has multidimensional aspects. Everyone must undergo this phase of life at his/her own life. In Ayurveda, Jara (ageing) is clearly defined as that which has lost age means become old by the act of degeneration of bodily tissues and organs. It is described of two types- Kalaja jara and Akalaja jara. The Kalaja jara (timely ageing) can be regarded as chronological ageing where Dhatukshaya occurs whereas the Akalajajara (premature ageing) which occurs untimely i.e., before its prescribed time it can be regarded as biological ageing and is more intense than that of the chronological ageing. Several concepts are reported in Ayurveda regarding ageing process e.g, decade wise ageing process is described by Acharya Vagbhat and Sharangdhara. According to them one particular bodily feature is being degraded by each decade of lifespan, in the same way multiple theories are also analyzed in contemporary science. The whole biology of ageing has been dealt in present article within the Ayurvedic frame.